Skip to main content
SpringerLink
Log in
Book cover

Nanotheranostics for Cancer Applications pp 163–205Cite as

Delivery of Cancer Nanotherapeutics

  • Chapter
  • First Online:

Part of the book series: Bioanalysis ((BIOANALYSIS,volume 5))

Abstract

Cancer nanotherapeutics comprise the main application of nanotechnology to healthcare and are administered intravenously for faster action and maximal bioavailability. As nanotherapeutics become more clinically established, a fundamental understanding of their interactions in vivo is necessary in order to better design these medicines to reach their target site in sufficient dose. The physicochemical properties of nanoparticles (e.g., size, shape, charge, and surface properties) determine their biological interactions in vivo. These properties, in addition to the tumor microenvironment, influence the dose of nanotherapeutics accumulating in tumors and within cancer cells. For instance, once injected, nanotherapeutics encounter multiple barriers in the body before they reach the tumor, after which they encounter cellular and intracellular obstacles. The route of administration is an important parameter for investigation, as the fraction of nanoparticles and therefore their therapeutic payload concentration at the disease site are consequently determined by barriers presented following intravenous or intraperitoneal administration. In this chapter, we aim to provide an overview of the different delivery methods used for clinical administration of cancer nanotherapeutics and discuss biological barriers to their delivery and how these could be overcome. This knowledge can aid in the better design of nanotherapeutics, with a focus on injectable formulations.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Peer, D., Karp, J.M., Hong, S., Farokhzad, O.C., Margalit, R., Langer, R.: Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2(12), 751–760 (2007). https://doi.org/10.1038/nnano.2007.387

    Article  Google Scholar 

  2. Bertrand, N., Wu, J., Xu, X., Kamaly, N., Farokhzad, O.C.: Cancer nanotechnology: the impact of passive and active targeting in the era of modern cancer biology. Adv. Drug Deliv. Rev. 66, 2–25 (2014). https://doi.org/10.1016/j.addr.2013.11.009

    Article  Google Scholar 

  3. Farokhzad, O.C., Langer, R.: Impact of nanotechnology on drug delivery. ACS Nano. 3(1), 16–20 (2009). https://doi.org/10.1021/nn900002m

    Article  Google Scholar 

  4. Wang, A.Z., Langer, R., Farokhzad, O.C.: Nanoparticle delivery of cancer drugs. Annu. Rev. Med. 63, 185–198 (2012). https://doi.org/10.1146/annurev-med-040210-162544

    Article  Google Scholar 

  5. Heath, J.R., Davis, M.E.: Nanotechnology and cancer. Annu. Rev. Med. 59, 251–265 (2008). https://doi.org/10.1146/annurev.med.59.061506.185523

    Article  Google Scholar 

  6. Davis, M.E., Chen, Z.G., Shin, D.M.: Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat. Rev. Drug Discov. 7(9), 771–782 (2008). https://doi.org/10.1038/nrd2614

    Article  Google Scholar 

  7. Shi, J., Xiao, Z., Kamaly, N., Farokhzad, O.C.: Self-assembled targeted nanoparticles: evolution of technologies and bench to bedside translation. Acc. Chem. Res. 44(10), 1123–1134 (2011). https://doi.org/10.1021/ar200054n

    Article  Google Scholar 

  8. Kamaly, N., Yameen, B., Wu, J., Farokhzad, O.C.: Degradable controlled-release polymers and polymeric nanoparticles: mechanisms of controlling drug release. Chem. Rev. 116(4), 2602–2663 (2016). https://doi.org/10.1021/acs.chemrev.5b00346

    Article  Google Scholar 

  9. Chen, G., Roy, I., Yang, C., Prasad, P.N.: Nanochemistry and nanomedicine for nanoparticle-based diagnostics and therapy. Chem. Rev. 116(5), 2826–2885 (2016). https://doi.org/10.1021/acs.chemrev.5b00148

    Article  Google Scholar 

  10. Stuart, M.A., Huck, W.T., Genzer, J., Muller, M., Ober, C., Stamm, M., Sukhorukov, G.B., Szleifer, I., Tsukruk, V.V., Urban, M., Winnik, F., Zauscher, S., Luzinov, I., Minko, S.: Emerging applications of stimuli-responsive polymer materials. Nat. Mater. 9(2), 101–113 (2010). https://doi.org/10.1038/nmat2614

    Article  Google Scholar 

  11. Pacardo, D.B., Ligler, F.S., Gu, Z.: Programmable nanomedicine: synergistic and sequential drug delivery systems. Nanoscale. 7(8), 3381–3391 (2015). https://doi.org/10.1039/c4nr07677j

    Article  Google Scholar 

  12. Mura, S., Nicolas, J., Couvreur, P.: Stimuli-responsive nanocarriers for drug delivery. Nat. Mater. 12(11), 991–1003 (2013). https://doi.org/10.1038/nmat3776

    Article  Google Scholar 

  13. Koetting, M.C., Peters, J.T., Steichen, S.D., Peppas, N.A.: Stimulus-responsive hydrogels: theory, modern advances, and applications. Mater. Sci. Eng. R. Rep. 93, 1–49 (2015). https://doi.org/10.1016/j.mser.2015.04.001

    Article  Google Scholar 

  14. Torchilin, V.P.: Multifunctional, stimuli-sensitive nanoparticulate systems for drug delivery. Nat. Rev. Drug Discov. 13(11), 813–827 (2014). https://doi.org/10.1038/nrd4333

    Article  Google Scholar 

  15. de la Rica, R., Aili, D., Stevens, M.M.: Enzyme-responsive nanoparticles for drug release and diagnostics. Adv. Drug Deliv. Rev. 64(11), 967–978 (2012). https://doi.org/10.1016/j.addr.2012.01.002

  16. Correa, S., Dreaden, E.C., Gu, L., Hammond, P.T.: Engineering nanolayered particles for modular drug delivery. J. Control. Release. (2016). https://doi.org/10.1016/j.jconrel.2016.01.040

  17. Kemp, J.A., Shim, M.S., Heo, C.Y., Kwon, Y.J.: “Combo” nanomedicine: co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy. Adv. Drug Deliv. Rev. 98, 3–18 (2016). https://doi.org/10.1016/j.addr.2015.10.019

    Article  Google Scholar 

  18. Xu, X., Ho, W., Zhang, X., Bertrand, N., Farokhzad, O.: Cancer nanomedicine: from targeted delivery to combination therapy. Trends Mol. Med. 21(4), 223–232 (2015). https://doi.org/10.1016/j.molmed.2015.01.001

    Article  Google Scholar 

  19. Gref, R., Minamitake, Y., Peracchia, M.T., Trubetskoy, V., Torchilin, V., Langer, R.: Biodegradable long-circulating polymeric nanospheres. Science. 263(5153), 1600–1603 (1994)

    Article  Google Scholar 

  20. Hamidi, M., Azadi, A., Rafiei, P.: Pharmacokinetic consequences of pegylation. Drug Deliv. 13(6), 399–409 (2006). https://doi.org/10.1080/10717540600814402

    Article  Google Scholar 

  21. Maeda, H.: Tumor-selective delivery of macromolecular drugs via the EPR effect: background and future prospects. Bioconjug. Chem. 21(5), 797–802 (2010). https://doi.org/10.1021/bc100070g

    Article  Google Scholar 

  22. Matsumura, Y., Maeda, H.: A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs. Cancer Res. 46(12 Pt 1), 6387–6392 (1986)

    Google Scholar 

  23. Carmeliet, P., Jain, R.K.: Angiogenesis in cancer and other diseases. Nature. 407(6801), 249–257 (2000). https://doi.org/10.1038/35025220

    Article  Google Scholar 

  24. Kamaly, N., Xiao, Z., Valencia, P.M., Radovic-Moreno, A.F., Farokhzad, O.C.: Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem. Soc. Rev. 41(7), 2971–3010 (2012). https://doi.org/10.1039/c2cs15344k

    Article  Google Scholar 

  25. Shi, J., Kantoff, P.W., Wooster, R., Farokhzad, O.C.: Cancer nanomedicine: progress, challenges and opportunities. Nat. Rev. Cancer. 17(1), 20–37 (2017). https://doi.org/10.1038/nrc.2016.108

    Article  Google Scholar 

  26. Allen, T.M., Chonn, A.: Large unilamellar liposomes with low uptake into the reticuloendothelial system. FEBS Lett. 223(1), 42–46 (1987). https://doi.org/10.1016/0014-5793(87)80506-9

    Article  Google Scholar 

  27. Barenholz, Y.: Doxil(R)--the first FDA-approved nano-drug: lessons learned. J. Control. Release. 160(2), 117–134 (2012). https://doi.org/10.1016/j.jconrel.2012.03.020

    Article  Google Scholar 

  28. Prabhakar, U., Maeda, H., Jain, R.K., Sevick-Muraca, E.M., Zamboni, W., Farokhzad, O.C., Barry, S.T., Gabizon, A., Grodzinski, P., Blakey, D.C.: Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology. Cancer Res. 73(8), 2412–2417 (2013). https://doi.org/10.1158/0008-5472.CAN-12-4561

    Article  Google Scholar 

  29. Hrkach, J., Von Hoff, D., Mukkaram Ali, M., Andrianova, E., Auer, J., Campbell, T., De Witt, D., Figa, M., Figueiredo, M., Horhota, A., Low, S., McDonnell, K., Peeke, E., Retnarajan, B., Sabnis, A., Schnipper, E., Song, J.J., Song, Y.H., Summa, J., Tompsett, D., Troiano, G., Van Geen Hoven, T., Wright, J., LoRusso, P., Kantoff, P.W., Bander, N.H., Sweeney, C., Farokhzad, O.C., Langer, R., Zale, S.: Preclinical development and clinical translation of a PSMA-targeted docetaxel nanoparticle with a differentiated pharmacological profile. Sci. Transl. Med. 4(128), 128ra139 (2012). https://doi.org/10.1126/scitranslmed.3003651

    Article  Google Scholar 

  30. Eliasof, S., Lazarus, D., Peters, C.G., Case, R.I., Cole, R.O., Hwang, J., Schluep, T., Chao, J., Lin, J., Yen, Y., Han, H., Wiley, D.T., Zuckerman, J.E., Davis, M.E.: Correlating preclinical animal studies and human clinical trials of a multifunctional, polymeric nanoparticle. Proc. Natl. Acad. Sci. U. S. A. 110(37), 15127–15132 (2013). https://doi.org/10.1073/pnas.1309566110

    Article  Google Scholar 

  31. Zuckerman, J.E., Gritli, I., Tolcher, A., Heidel, J.D., Lim, D., Morgan, R., Chmielowski, B., Ribas, A., Davis, M.E., Yen, Y.: Correlating animal and human phase Ia/Ib clinical data with CALAA-01, a targeted, polymer-based nanoparticle containing siRNA. Proc. Natl. Acad. Sci. U. S. A. 111(31), 11449–11454 (2014). https://doi.org/10.1073/pnas.1411393111

    Article  Google Scholar 

  32. Stylianopoulos, T., Jain, R.K.: Combining two strategies to improve perfusion and drug delivery in solid tumors. Proc. Natl. Acad. Sci. U. S. A. 110(46), 18632–18637 (2013). https://doi.org/10.1073/pnas.1318415110

    Article  Google Scholar 

  33. Miller, M.A., Gadde, S., Pfirschke, C., Engblom, C., Sprachman, M.M., Kohler, R.H., Yang, K.S., Laughney, A.M., Wojtkiewicz, G., Kamaly, N., Bhonagiri, S., Pittet, M.J., Farokhzad, O.C., Weissleder, R.: Predicting therapeutic nanomedicine efficacy using a companion magnetic resonance imaging nanoparticle. Sci. Transl. Med. 7(314), 314ra183 (2015). https://doi.org/10.1126/scitranslmed.aac6522

    Article  Google Scholar 

  34. Chauhan, V.P., Stylianopoulos, T., Martin, J.D., Popovic, Z., Chen, O., Kamoun, W.S., Bawendi, M.G., Fukumura, D., Jain, R.K.: Normalization of tumour blood vessels improves the delivery of nanomedicines in a size-dependent manner. Nat. Nanotechnol. 7(6), 383–388 (2012). https://doi.org/10.1038/nnano.2012.45

    Article  Google Scholar 

  35. Foster, C., Watson, A., Kaplinsky, J., Kamaly, N.: Improved Targeting of Cancers with Nanotherapeutics. Methods Mol. Biol. 1530, 13–37 (2017). https://doi.org/10.1007/978-1-4939-6646-2_2

    Article  Google Scholar 

  36. Wang, A.Z., Gu, F., Zhang, L., Chan, J.M., Radovic-Moreno, A., Shaikh, M.R., Farokhzad, O.C.: Biofunctionalized targeted nanoparticles for therapeutic applications. Expert Opin. Biol. Ther. 8(8), 1063–1070 (2008). https://doi.org/10.1517/14712598.8.8.1063

    Article  Google Scholar 

  37. Wicki, A., Witzigmann, D., Balasubramanian, V., Huwyler, J.: Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. J. Control. Release. 200, 138–157 (2015). https://doi.org/10.1016/j.jconrel.2014.12.030

    Article  Google Scholar 

  38. Lyseng-Williamson, K.A., Duggan, S.T., Keating, G.M.: Pegylated liposomal doxorubicin: a guide to its use in various malignancies. BioDrugs. 27(5), 533–540 (2013). https://doi.org/10.1007/s40259-013-0070-1

    Article  Google Scholar 

  39. Harrison, M., Tomlinson, D., Stewart, S.: Liposomal-entrapped doxorubicin: an active agent in AIDS-related Kaposi's sarcoma. J. Clin. Oncol. 13(4), 914–920 (1995)

    Article  Google Scholar 

  40. Money-Kyrle, J.F., Bates, F., Ready, J., Gazzard, B.G., Phillips, R.H., Boag, F.C.: Liposomal daunorubicin in advanced Kaposi's sarcoma: a phase II study. Clin. Oncol. (R. Coll. Radiol.). 5(6), 367–371 (1993)

    Article  Google Scholar 

  41. Rosenthal, E., Poizot-Martin, I., Saint-Marc, T., Spano, J.P., Cacoub, P., Group DNXS: Phase IV study of liposomal daunorubicin (DaunoXome) in AIDS-related Kaposi sarcoma. Am. J. Clin. Oncol. 25(1), 57–59 (2002)

    Article  Google Scholar 

  42. Khemapech, N., Oranratanaphan, S., Termrungruanglert, W., Lertkhachonsuk, R., Vasurattana, A.: Salvage chemotherapy in recurrent platinum-resistant or refractory epithelial ovarian cancer with Carboplatin and distearoylphosphatidylcholine pegylated liposomal Doxorubicin (lipo-dox(R)). Asian Pac. J. Cancer Prev. 14(3), 2131–2135 (2013)

    Article  Google Scholar 

  43. Glantz, M.J., Jaeckle, K.A., Chamberlain, M.C., Phuphanich, S., Recht, L., Swinnen, L.J., Maria, B., LaFollette, S., Schumann, G.B., Cole, B.F., Howell, S.B.: A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clin. Cancer Res. 5(11), 3394–3402 (1999)

    Google Scholar 

  44. Batist, G., Ramakrishnan, G., Rao, C.S., Chandrasekharan, A., Gutheil, J., Guthrie, T., Shah, P., Khojasteh, A., Nair, M.K., Hoelzer, K., Tkaczuk, K., Park, Y.C., Lee, L.W.: Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer. J. Clin. Oncol. 19(5), 1444–1454 (2001)

    Article  Google Scholar 

  45. FDA approves liposomal vincristine (Marqibo) for rare leukemia. Oncology (Williston Park). 26(9), 841 (2012)

    Google Scholar 

  46. Silverman, J.A., Deitcher, S.R.: Marqibo(R) (vincristine sulfate liposome injection) improves the pharmacokinetics and pharmacodynamics of vincristine. Cancer Chemother. Pharmacol. 71(3), 555–564 (2013). https://doi.org/10.1007/s00280-012-2042-4

    Article  Google Scholar 

  47. Allen, T.M., Cullis, P.R.: Liposomal drug delivery systems: from concept to clinical applications. Adv. Drug Deliv. Rev. 65(1), 36–48 (2013). https://doi.org/10.1016/j.addr.2012.09.037

    Article  Google Scholar 

  48. Gabizon, A., Shmeeda, H., Barenholz, Y.: Pharmacokinetics of pegylated liposomal Doxorubicin: review of animal and human studies. Clin. Pharmacokinet. 42(5), 419–436 (2003). https://doi.org/10.2165/00003088-200342050-00002

    Article  Google Scholar 

  49. Kratz, F.: Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles. J. Control. Release. 132(3), 171–183 (2008). https://doi.org/10.1016/j.jconrel.2008.05.010

    Article  Google Scholar 

  50. Singla, A.K., Garg, A., Aggarwal, D.: Paclitaxel and its formulations. Int. J. Pharm. 235(1-2), 179–192 (2002)

    Article  Google Scholar 

  51. Kundranda, M.N., Niu, J.: Albumin-bound paclitaxel in solid tumors: clinical development and future directions. Drug Des. Devel. Ther. 9, 3767–3777 (2015). https://doi.org/10.2147/DDDT.S88023

    Article  Google Scholar 

  52. Liu, Z., Chen, X.: Simple bioconjugate chemistry serves great clinical advances: albumin as a versatile platform for diagnosis and precision therapy. Chem. Soc. Rev. 45(5), 1432–1456 (2016). https://doi.org/10.1039/c5cs00158g

    Article  Google Scholar 

  53. Ibrahim, N.K., Samuels, B., Page, R., Doval, D., Patel, K.M., Rao, S.C., Nair, M.K., Bhar, P., Desai, N., Hortobagyi, G.N.: Multicenter phase II trial of ABI-007, an albumin-bound paclitaxel, in women with metastatic breast cancer. J. Clin. Oncol. 23(25), 6019–6026 (2005). https://doi.org/10.1200/JCO.2005.11.013

    Article  Google Scholar 

  54. Rajeshkumar, N.V., Yabuuchi, S., Pai, S.G., Tong, Z., Hou, S., Bateman, S., Pierce, D.W., Heise, C., Von Hoff, D.D., Maitra, A., Hidalgo, M.: Superior therapeutic efficacy of nab-paclitaxel over cremophor-based paclitaxel in locally advanced and metastatic models of human pancreatic cancer. Br. J. Cancer. 115(4), 442–453 (2016). https://doi.org/10.1038/bjc.2016.215

    Article  Google Scholar 

  55. Park, S.R., Oh, D.Y., Kim, D.W., Kim, T.Y., Heo, D.S., Bang, Y.J., Kim, N.K., Kang, W.K., Kim, H.T., Im, S.A., Suh, J.H., Kim, H.K.: A multi-center, late phase II clinical trial of Genexol (paclitaxel) and cisplatin for patients with advanced gastric cancer. Oncol. Rep. 12(5), 1059–1064 (2004)

    Google Scholar 

  56. Kim, T.Y., Kim, D.W., Chung, J.Y., Shin, S.G., Kim, S.C., Heo, D.S., Kim, N.K., Bang, Y.J.: Phase I and pharmacokinetic study of Genexol-PM, a cremophor-free, polymeric micelle-formulated paclitaxel, in patients with advanced malignancies. Clin. Cancer Res. 10(11), 3708–3716 (2004). https://doi.org/10.1158/1078-0432.CCR-03-065510/11/3708

    Article  Google Scholar 

  57. Ediriwickrema, A., Zhou, J., Deng, Y., Saltzman, W.M.: Multi-layered nanoparticles for combination gene and drug delivery to tumors. Biomaterials. 35(34), 9343–9354 (2014). https://doi.org/10.1016/j.biomaterials.2014.07.043

    Article  Google Scholar 

  58. Gradishar, W.J., Tjulandin, S., Davidson, N., Shaw, H., Desai, N., Bhar, P., Hawkins, M., O'Shaughnessy, J.: Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J. Clin. Oncol. 23(31), 7794–7803 (2005). https://doi.org/10.1200/JCO.2005.04.937

    Article  Google Scholar 

  59. Nishiyama, N., Matsumura, Y., Kataoka, K.: Development of polymeric micelles for targeting intractable cancers. Cancer Sci. (2016). https://doi.org/10.1111/cas.12960

  60. Cabral, H., Kataoka, K.: Progress of drug-loaded polymeric micelles into clinical studies. J. Control. Release. 190, 465–476 (2014). https://doi.org/10.1016/j.jconrel.2014.06.042

    Article  Google Scholar 

  61. Batrakova, E.V., Kabanov, A.V.: Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers. J. Control. Release. 130(2), 98–106 (2008). https://doi.org/10.1016/j.jconrel.2008.04.013

    Article  Google Scholar 

  62. Ibrahim, N.K., Desai, N., Legha, S., Soon-Shiong, P., Theriault, R.L., Rivera, E., Esmaeli, B., Ring, S.E., Bedikian, A., Hortobagyi, G.N., Ellerhorst, J.A.: Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. Clin. Cancer Res. 8(5), 1038–1044 (2002)

    Google Scholar 

  63. Sparreboom, A., Scripture, C.D., Trieu, V., Williams, P.J., De, T., Yang, A., Beals, B., Figg, W.D., Hawkins, M., Desai, N.: Comparative preclinical and clinical pharmacokinetics of a cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in Cremophor (Taxol). Clin. Cancer Res. 11(11), 4136–4143 (2005). https://doi.org/10.1158/1078-0432.CCR-04-2291

    Article  Google Scholar 

  64. Duncan, R.: Polymer therapeutics: top 10 selling pharmaceuticals - what next? J. Control. Release. 190, 371–380 (2014). https://doi.org/10.1016/j.jconrel.2014.05.001

    Article  Google Scholar 

  65. Duncan, R.: Polymer conjugates as anticancer nanomedicines. Nat. Rev. Cancer. 6(9), 688–701 (2006). https://doi.org/10.1038/nrc1958

    Article  Google Scholar 

  66. Dinndorf, P.A., Gootenberg, J., Cohen, M.H., Keegan, P., Pazdur, R.: FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Oncologist. 12(8), 991–998 (2007). https://doi.org/10.1634/theoncologist.12-8-991

    Article  Google Scholar 

  67. Venkatakrishnan, K., Liu, Y., Noe, D., Mertz, J., Bargfrede, M., Marbury, T., Farbakhsh, K., Oliva, C., Milton, A.: Pharmacokinetics and pharmacodynamics of liposomal mifamurtide in adult volunteers with mild or moderate hepatic impairment. Br. J. Clin. Pharmacol. 77(6), 998–1010 (2014). https://doi.org/10.1111/bcp.12261

    Article  Google Scholar 

  68. Rivera Gil, P., Huhn, D., del Mercato, L.L., Sasse, D., Parak, W.J.: Nanopharmacy: inorganic nanoscale devices as vectors and active compounds. Pharmacol. Res. 62(2), 115–125 (2010). https://doi.org/10.1016/j.phrs.2010.01.009

    Article  Google Scholar 

  69. Bleyer, W.A.: Intrathecal depot cytarabine therapy: a welcome addition to a limited armamentarium. Clin. Cancer Res. 5, 3349–3351 (1999)

    Google Scholar 

  70. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&applno=021660. Accessed 11 Oct 2017

  71. http://www.abraxane.com/mbc/. Accessed 11 Oct 2017

  72. http://www.bausch.com/ecp/our-products/rx-pharmaceuticals/rx-pharmaceuticals/visudyne-verteporfin-for-injection. Accessed 11 Oct 2017

  73. http://www.centerwatch.com/drug-information/fda-approved-drugs/drug/616/visudyne-verteporfin-for-injection. Accessed 11 Oct 2017

  74. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=cc8f105c-c8ee-4c57-86ee-ee6bf917cf78. Accessed 11 Oct 2017

  75. Espelin, C.W., Leonard, S.C., Geretti, E., Wickham, T.J., Hendriks, B.S.: Dual HER2 targeting with trastuzumab and liposomal-encapsulated doxorubicin (MM-302) demonstrates synergistic antitumor activity in breast and gastric cancer. Cancer Res. 76(6), 1517–1527 (2016). https://doi.org/10.1158/0008-5472.CAN-15-1518

    Article  Google Scholar 

  76. Davis, M.E., Zuckerman, J.E., Choi, C.H., Seligson, D., Tolcher, A., Alabi, C.A., Yen, Y., Heidel, J.D., Ribas, A.: Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature. 464(7291), 1067–1070 (2010). https://doi.org/10.1038/nature08956

    Article  Google Scholar 

  77. Kannan, R.M., Nance, E., Kannan, S., Tomalia, D.A.: Emerging concepts in dendrimer-based nanomedicine: from design principles to clinical applications. J. Intern. Med. 276(6), 579–617 (2014). https://doi.org/10.1111/joim.12280

    Article  Google Scholar 

  78. Roy, U., Rodriguez, J., Barber, P., das Neves, J., Sarmento, B., Nair, M.: The potential of HIV-1 nanotherapeutics: from in vitro studies to clinical trials. Nanomedicine (Lond.). 10(24), 3597–3609 (2015). https://doi.org/10.2217/nnm.15.160

    Article  Google Scholar 

  79. Mignani, S., El Kazzouli, S., Bousmina, M., Majoral, J.P.: Expand classical drug administration ways by emerging routes using dendrimer drug delivery systems: a concise overview. Adv. Drug Deliv. Rev. 65(10), 1316–1330 (2013). https://doi.org/10.1016/j.addr.2013.01.001

    Article  Google Scholar 

  80. Dreaden, E.C., Mackey, M.A., Huang, X., Kang, B., El-Sayed, M.A.: Beating cancer in multiple ways using nanogold. Chem. Soc. Rev. 40(7), 3391–3404 (2011). https://doi.org/10.1039/c0cs00180e

    Article  Google Scholar 

  81. Anselmo, A.C., Mitragotri, S.: A review of clinical translation of inorganic nanoparticles. AAPS J. 17(5), 1041–1054 (2015). https://doi.org/10.1208/s12248-015-9780-2

    Article  Google Scholar 

  82. Giljohann, D.A., Seferos, D.S., Daniel, W.L., Massich, M.D., Patel, P.C., Mirkin, C.A.: Gold nanoparticles for biology and medicine. Angew. Chem. Int. Ed. Engl. 49(19), 3280–3294 (2010). https://doi.org/10.1002/anie.200904359

    Article  Google Scholar 

  83. Phillips, E., Penate-Medina, O., Zanzonico, P.B., Carvajal, R.D., Mohan, P., Ye, Y., Humm, J., Gonen, M., Kalaigian, H., Schoder, H., Strauss, H.W., Larson, S.M., Wiesner, U., Bradbury, M.S.: Clinical translation of an ultrasmall inorganic optical-PET imaging nanoparticle probe. Sci. Transl. Med. 6(260), 260ra149 (2014). https://doi.org/10.1126/scitranslmed.3009524

    Article  Google Scholar 

  84. Yang, Y., Yu, C.: Advances in silica based nanoparticles for targeted cancer therapy. Nanomedicine. 12(2), 317–332 (2016). https://doi.org/10.1016/j.nano.2015.10.018

    Article  Google Scholar 

  85. Meng, H., Wang, M., Liu, H., Liu, X., Situ, A., Wu, B., Ji, Z., Chang, C.H., Nel, A.E.: Use of a lipid-coated mesoporous silica nanoparticle platform for synergistic gemcitabine and paclitaxel delivery to human pancreatic cancer in mice. ACS Nano. 9(4), 3540–3557 (2015). https://doi.org/10.1021/acsnano.5b00510

    Article  Google Scholar 

  86. Laurent, S., Forge, D., Port, M., Roch, A., Robic, C., Vander Elst, L., Muller, R.N.: Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem. Rev. 108(6), 2064–2110 (2008). https://doi.org/10.1021/cr068445e

    Article  Google Scholar 

  87. Maier-Hauff, K., Ulrich, F., Nestler, D., Niehoff, H., Wust, P., Thiesen, B., Orawa, H., Budach, V., Jordan, A.: Efficacy and safety of intratumoral thermotherapy using magnetic iron-oxide nanoparticles combined with external beam radiotherapy on patients with recurrent glioblastoma multiforme. J. Neurooncol. 103(2), 317–324 (2011). https://doi.org/10.1007/s11060-010-0389-0

    Article  Google Scholar 

  88. Maggiorella, L., Barouch, G., Devaux, C., Pottier, A., Deutsch, E., Bourhis, J., Borghi, E., Levy, L.: Nanoscale radiotherapy with hafnium oxide nanoparticles. Future Oncol. 8(9), 1167–1181 (2012). https://doi.org/10.2217/fon.12.96

    Article  Google Scholar 

  89. Field, J.A., Luna-Velasco, A., Boitano, S.A., Shadman, F., Ratner, B.D., Barnes, C., Sierra-Alvarez, R.: Cytotoxicity and physicochemical properties of hafnium oxide nanoparticles. Chemosphere. 84(10), 1401–1407 (2011). https://doi.org/10.1016/j.chemosphere.2011.04.067

    Article  Google Scholar 

  90. Park, B.H., Hwang, T., Liu, T.C., Sze, D.Y., Kim, J.S., Kwon, H.C., Oh, S.Y., Han, S.Y., Yoon, J.H., Hong, S.H., Moon, A., Speth, K., Park, C., Ahn, Y.J., Daneshmand, M., Rhee, B.G., Pinedo, H.M., Bell, J.C., Kirn, D.H.: Use of a targeted oncolytic poxvirus, JX-594, in patients with refractory primary or metastatic liver cancer: a phase I trial. Lancet Oncol. 9(6), 533–542 (2008). https://doi.org/10.1016/S1470-2045(08)70107-4

    Article  Google Scholar 

  91. Tolcher, A.W., Rodrigueza, W.V., Rasco, D.W., Patnaik, A., Papadopoulos, K.P., Amaya, A., Moore, T.D., Gaylor, S.K., Bisgaier, C.L., Sooch, M.P., Woolliscroft, M.J., Messmann, R.A.: A phase 1 study of the BCL2-targeted deoxyribonucleic acid inhibitor (DNAi) PNT2258 in patients with advanced solid tumors. Cancer Chemother. Pharmacol. 73(2), 363–371 (2014). https://doi.org/10.1007/s00280-013-2361-0

    Article  Google Scholar 

  92. Tabernero, J., Shapiro, G.I., LoRusso, P.M., Cervantes, A., Schwartz, G.K., Weiss, G.J., Paz-Ares, L., Cho, D.C., Infante, J.R., Alsina, M., Gounder, M.M., Falzone, R., Harrop, J., White, A.C., Toudjarska, I., Bumcrot, D., Meyers, R.E., Hinkle, G., Svrzikapa, N., Hutabarat, R.M., Clausen, V.A., Cehelsky, J., Nochur, S.V., Gamba-Vitalo, C., Vaishnaw, A.K., Sah, D.W., Gollob, J.A., Burris, H.A.: First-in-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement. Cancer Discov. 3(4), 406–417 (2013). https://doi.org/10.1158/2159-8290.CD-12-0429

    Article  Google Scholar 

  93. Schultheis, B., Strumberg, D., Santel, A., Vank, C., Gebhardt, F., Keil, O., Lange, C., Giese, K., Kaufmann, J., Khan, M., Drevs, J.: First-in-human phase I study of the liposomal RNA interference therapeutic Atu027 in patients with advanced solid tumors. J. Clin. Oncol. 32(36), 4141–4148 (2014). https://doi.org/10.1200/JCO.2013.55.0376

    Article  Google Scholar 

  94. Jensen, S.A., Day, E.S., Ko, C.H., Hurley, L.A., Luciano, J.P., Kouri, F.M., Merkel, T.J., Luthi, A.J., Patel, P.C., Cutler, J.I., Daniel, W.L., Scott, A.W., Rotz, M.W., Meade, T.J., Giljohann, D.A., Mirkin, C.A., Stegh, A.H.: Spherical nucleic acid nanoparticle conjugates as an RNAi-based therapy for glioblastoma. Sci. Transl. Med. 5(209), 209ra152 (2013). https://doi.org/10.1126/scitranslmed.3006839

    Article  Google Scholar 

  95. Islam, M.A., Reesor, E.K., Xu, Y., Zope, H.R., Zetter, B.R., Shi, J.: Biomaterials for mRNA delivery. Biomater. Sci. 3(12), 1519–1533 (2015). https://doi.org/10.1039/c5bm00198f

    Article  Google Scholar 

  96. Park, J., Wrzesinski, S.H., Stern, E., Look, M., Criscione, J., Ragheb, R., Jay, S.M., Demento, S.L., Agawu, A., Licona Limon, P., Ferrandino, A.F., Gonzalez, D., Habermann, A., Flavell, R.A., Fahmy, T.M.: Combination delivery of TGF-beta inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy. Nat. Mater. 11(10), 895–905 (2012). https://doi.org/10.1038/nmat3355

    Article  Google Scholar 

  97. Lee, I.H., An, S., Yu, M.K., Kwon, H.K., Im, S.H., Jon, S.: Targeted chemoimmunotherapy using drug-loaded aptamer-dendrimer bioconjugates. J. Control. Release. 155(3), 435–441 (2011). https://doi.org/10.1016/j.jconrel.2011.05.025

    Article  Google Scholar 

  98. Yildiz, I., Shukla, S., Steinmetz, N.F.: Applications of viral nanoparticles in medicine. Curr. Opin. Biotechnol. 22(6), 901–908 (2011). https://doi.org/10.1016/j.copbio.2011.04.020

    Article  Google Scholar 

  99. Czapar, A.E., Zheng, Y.R., Riddell, I.A., Shukla, S., Awuah, S.G., Lippard, S.J., Steinmetz, N.F.: Tobacco mosaic virus delivery of phenanthriplatin for cancer therapy. ACS Nano. 10(4), 4119–4126 (2016). https://doi.org/10.1021/acsnano.5b07360

    Article  Google Scholar 

  100. Chow, E.K., Zhang, X.Q., Chen, M., Lam, R., Robinson, E., Huang, H., Schaffer, D., Osawa, E., Goga, A., Ho, D.: Nanodiamond therapeutic delivery agents mediate enhanced chemoresistant tumor treatment. Sci. Transl. Med. 3(73), 73ra21 (2011). https://doi.org/10.1126/scitranslmed.3001713

    Article  Google Scholar 

  101. Mochalin, V.N., Pentecost, A., Li, X.M., Neitzel, I., Nelson, M., Wei, C., He, T., Guo, F., Gogotsi, Y.: Adsorption of drugs on nanodiamond: toward development of a drug delivery platform. Mol. Pharm. 10(10), 3728–3735 (2013). https://doi.org/10.1021/mp400213z

    Article  Google Scholar 

  102. Ho, D.: Nanodiamond-based chemotherapy and imaging. Cancer Treat. Res. 166, 85–102 (2015). https://doi.org/10.1007/978-3-319-16555-4_4

    Article  Google Scholar 

  103. Jiang, T., Sun, W., Zhu, Q., Burns, N.A., Khan, S.A., Mo, R., Gu, Z.: Furin-mediated sequential delivery of anticancer cytokine and small-molecule drug shuttled by graphene. Adv. Mater. 27(6), 1021–1028 (2015). https://doi.org/10.1002/adma.201404498

    Article  Google Scholar 

  104. Liu, Z., Robinson, J.T., Sun, X., Dai, H.: PEGylated nanographene oxide for delivery of water-insoluble cancer drugs. J. Am. Chem. Soc. 130(33), 10876–10877 (2008). https://doi.org/10.1021/ja803688x

    Article  Google Scholar 

  105. Maldonado, R.A., LaMothe, R.A., Ferrari, J.D., Zhang, A.H., Rossi, R.J., Kolte, P.N., Griset, A.P., O'Neil, C., Altreuter, D.H., Browning, E., Johnston, L., Farokhzad, O.C., Langer, R., Scott, D.W., von Andrian, U.H., Kishimoto, T.K.: Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance. Proc. Natl. Acad. Sci. U. S. A. 112(2), E156–E165 (2015). https://doi.org/10.1073/pnas.1408686111

    Article  Google Scholar 

  106. Ilyinskii, P.O., Roy, C.J., O'Neil, C.P., Browning, E.A., Pittet, L.A., Altreuter, D.H., Alexis, F., Tonti, E., Shi, J., Basto, P.A., Iannacone, M., Radovic-Moreno, A.F., Langer, R.S., Farokhzad, O.C., von Andrian, U.H., Johnston, L.P., Kishimoto, T.K.: Adjuvant-carrying synthetic vaccine particles augment the immune response to encapsulated antigen and exhibit strong local immune activation without inducing systemic cytokine release. Vaccine. 32(24), 2882–2895 (2014). https://doi.org/10.1016/j.vaccine.2014.02.027

    Article  Google Scholar 

  107. Chen, E.C., Fathi, A.T., Brunner, A.M.: Reformulating acute myeloid leukemia: liposomalcytarabine and daunorubicin (CPX-351) as an emerging therapy for secondary AML. Onco. Targets. Ther. 11, 3425–3434 (2017). https://doi.org/10.2147/OTT.S141212

  108. Ilinskaya, A.N., Dobrovolskaia, M.A.: Understanding the immunogenicity and antigenicity of nanomaterials: past, present and future. Toxicol. Appl. Pharmacol. 299, 70–77 (2016). https://doi.org/10.1016/j.taap.2016.01.005

    Article  Google Scholar 

  109. Desai, N.: Challenges in development of nanoparticle-based therapeutics. AAPS J. 14(2), 282–295 (2012). https://doi.org/10.1208/s12248-012-9339-4

    Article  Google Scholar 

  110. Mahon, E., Salvati, A., Baldelli Bombelli, F., Lynch, I., Dawson, K.A.: Designing the nanoparticle-biomolecule interface for “targeting and therapeutic delivery”. J. Control. Release. 161(2), 164–174 (2012). https://doi.org/10.1016/j.jconrel.2012.04.009

    Article  Google Scholar 

  111. Blanco, E., Shen, H., Ferrari, M.: Principles of nanoparticle design for overcoming biological barriers to drug delivery. Nat. Biotechnol. 33(9), 941–951 (2015). https://doi.org/10.1038/nbt.3330

    Article  Google Scholar 

  112. Mahmoudi, M., Lynch, I., Ejtehadi, M.R., Monopoli, M.P., Bombelli, F.B., Laurent, S.: Protein-nanoparticle interactions: opportunities and challenges. Chem. Rev. 111(9), 5610–5637 (2011). https://doi.org/10.1021/cr100440g

    Article  Google Scholar 

  113. Miller, M.A., Zheng, Y.R., Gadde, S., Pfirschke, C., Zope, H., Engblom, C., Kohler, R.H., Iwamoto, Y., Yang, K.S., Askevold, B., Kolishetti, N., Pittet, M., Lippard, S.J., Farokhzad, O.C., Weissleder, R.: Tumour-associated macrophages act as a slow-release reservoir of nano-therapeutic Pt(IV) pro-drug. Nat. Commun. 6, 8692 (2015). https://doi.org/10.1038/ncomms9692

    Article  Google Scholar 

  114. Bednarski, M., Dudek, M., Knutelska, J., Nowinski, L., Sapa, J., Zygmunt, M., Nowak, G., Luty-Blocho, M., Wojnicki, M., Fitzner, K., Tesiorowski, M.: The influence of the route of administration of gold nanoparticles on their tissue distribution and basic biochemical parameters: In vivo studies. Pharmacol. Rep. 67(3), 405–409 (2015). https://doi.org/10.1016/j.pharep.2014.10.019

    Article  Google Scholar 

  115. Gurney, H.: How to calculate the dose of chemotherapy. Br. J. Cancer. 86(8), 1297–1302 (2002). https://doi.org/10.1038/sj.bjc.6600139

    Article  Google Scholar 

  116. Zee-Cheng, R.K., Cheng, C.C.: Delivery of anticancer drugs. Methods Find. Exp. Clin. Pharmacol. 11(7-8), 439–529 (1989)

    Google Scholar 

  117. Collins, J.M.: Pharmacologic rationale for regional drug delivery. J. Clin. Oncol. 2(5), 498–504 (1984)

    Article  Google Scholar 

  118. Markman, M.: Intraperitoneal drug delivery of antineoplastics. Drugs. 61(8), 1057–1065 (2001)

    Article  Google Scholar 

  119. Lokich, J., Anderson, N.: Dose intensity for bolus versus infusion chemotherapy administration: review of the literature for 27 anti-neoplastic agents. Ann. Oncol. 8(1), 15–25 (1997)

    Article  Google Scholar 

  120. Harivardhan Reddy, L., Sharma, R.K., Chuttani, K., Mishra, A.K., Murthy, R.S.: Influence of administration route on tumor uptake and biodistribution of etoposide loaded solid lipid nanoparticles in Dalton's lymphoma tumor bearing mice. J. Control. Release. 105(3), 185–198 (2005). https://doi.org/10.1016/j.jconrel.2005.02.028

    Article  Google Scholar 

  121. Dakwar, G.R., Shariati, M., Willaert, W., Ceelen, W., De Smedt, S.C., Remaut, K.: Nanomedicine-based intraperitoneal therapy for the treatment of peritoneal carcinomatosis - Mission possible? Adv. Drug Deliv. Rev. (2016). https://doi.org/10.1016/j.addr.2016.07.001

  122. Ceelen, W.P.: Peritoneal Carcinomatosis : A Multidisciplinary Approach. Springer, New York (2007)

    Book  Google Scholar 

  123. Bajaj, G., Yeo, Y.: Drug delivery systems for intraperitoneal therapy. Pharm. Res. 27(5), 735–738 (2010). https://doi.org/10.1007/s11095-009-0031-z

    Article  Google Scholar 

  124. Lu, Z., Guillaume Wientjes, M., Au, J.L.-S.: Development of drug-loaded particles for intraperitoneal therapy. In: Ceelen, W.P., Levine, E. (eds.) Intraperitoneal Cancer Therapy: Principles and Practice, pp. 341–345. CRC Press, Boca Raton, FL, USA (2015)

    Google Scholar 

  125. Anwer, K., Barnes, M.N., Fewell, J., Lewis, D.H., Alvarez, R.D.: Phase-I clinical trial of IL-12 plasmid/lipopolymer complexes for the treatment of recurrent ovarian cancer. Gene Ther. 17(3), 360–369 (2010). https://doi.org/10.1038/gt.2009.159

    Article  Google Scholar 

  126. Anwer, K., Kelly, F.J., Chu, C., Fewell, J.G., Lewis, D., Alvarez, R.D.: Phase I trial of a formulated IL-12 plasmid in combination with carboplatin and docetaxel chemotherapy in the treatment of platinum-sensitive recurrent ovarian cancer. Gynecol. Oncol. 131(1), 169–173 (2013). https://doi.org/10.1016/j.ygyno.2013.07.081

    Article  Google Scholar 

  127. Alvarez, R.D., Sill, M.W., Davidson, S.A., Muller, C.Y., Bender, D.P., DeBernardo, R.L., Behbakht, K., Huh, W.K.: A phase II trial of intraperitoneal EGEN-001, an IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer: a gynecologic oncology group study. Gynecol. Oncol. 133(3), 433–438 (2014). https://doi.org/10.1016/j.ygyno.2014.03.571

    Article  Google Scholar 

  128. Williamson, S.K., Johnson, G.A., Maulhardt, H.A., Moore, K.M., McMeekin, D.S., Schulz, T.K., Reed, G.A., Roby, K.F., Mackay, C.B., Smith, H.J., Weir, S.J., Wick, J.A., Markman, M., diZerega, G.S., Baltezor, M.J., Espinosa, J., Decedue, C.J.: A phase I study of intraperitoneal nanoparticulate paclitaxel (Nanotax(R)) in patients with peritoneal malignancies. Cancer Chemother. Pharmacol. 75(5), 1075–1087 (2015). https://doi.org/10.1007/s00280-015-2737-4

    Article  Google Scholar 

  129. http://meetinglibrary.asco.org/content/152193-156. Accessed 11 Oct 2017

  130. Keizer, H.J., Pinedo, H.M.: Cancer chemotherapy: alternative routes of drug administration. A review. Cancer Drug Deliv. 2(2), 147–169 (1985)

    Article  Google Scholar 

  131. Biffi, R., De Braud, F., Orsi, F., Pozzi, S., Arnaldi, P., Goldhirsch, A., Rotmensz, N., Robertson, C., Bellomi, M., Andreoni, B.: A randomized, prospective trial of central venous ports connected to standard open-ended or Groshong catheters in adult oncology patients. Cancer. 92(5), 1204–1212 (2001)

    Article  Google Scholar 

  132. Biffi, R., de Braud, F., Orsi, F., Pozzi, S., Mauri, S., Goldhirsch, A., Nole, F., Andreoni, B.: Totally implantable central venous access ports for long-term chemotherapy. A prospective study analyzing complications and costs of 333 devices with a minimum follow-up of 180 days. Ann. Oncol. 9(7), 767–773 (1998)

    Article  Google Scholar 

  133. Zhang, X.Q., Xu, X., Bertrand, N., Pridgen, E., Swami, A., Farokhzad, O.C.: Interactions of nanomaterials and biological systems: implications to personalized nanomedicine. Adv. Drug Deliv. Rev. 64(13), 1363–1384 (2012). https://doi.org/10.1016/j.addr.2012.08.005

    Article  Google Scholar 

  134. Pridgen, E.M., Alexis, F., Farokhzad, O.C.: Polymeric nanoparticle drug delivery technologies for oral delivery applications. Expert Opin. Drug Deliv. 12(9), 1459–1473 (2015). https://doi.org/10.1517/17425247.2015.1018175

    Article  Google Scholar 

  135. Dunnhaupt, S., Kammona, O., Waldner, C., Kiparissides, C., Bernkop-Schnurch, A.: Nano-carrier systems: strategies to overcome the mucus gel barrier. Eur. J. Pharm. Biopharm. 96, 447–453 (2015). https://doi.org/10.1016/j.ejpb.2015.01.022

    Article  Google Scholar 

  136. Haque, S., Whittaker, M.R., McIntosh, M.P., Pouton, C.W., Kaminskas, L.M.: Disposition and safety of inhaled biodegradable nanomedicines: opportunities and challenges. Nanomedicine. 12(6), 1703–1724 (2016). https://doi.org/10.1016/j.nano.2016.03.002

    Article  Google Scholar 

  137. Kang, H., Gravier, J., Bao, K., Wada, H., Lee, J.H., Baek, Y., El Fakhri, G., Gioux, S., Rubin, B.P., Coll, J.L., Choi, H.S.: Renal clearable organic nanocarriers for bioimaging and drug delivery. Adv. Mater. (2016). https://doi.org/10.1002/adma.201601101

  138. Sarin, H.: Physiologic upper limits of pore size of different blood capillary types and another perspective on the dual pore theory of microvascular permeability. J. Angiogenes. Res. 2, 14 (2010). https://doi.org/10.1186/2040-2384-2-14

    Article  Google Scholar 

  139. Choi, H.S., Liu, W., Misra, P., Tanaka, E., Zimmer, J.P., Itty Ipe, B., Bawendi, M.G., Frangioni, J.V.: Renal clearance of quantum dots. Nat. Biotechnol. 25(10), 1165–1170 (2007). https://doi.org/10.1038/nbt1340

    Article  Google Scholar 

  140. Cabral, H., Matsumoto, Y., Mizuno, K., Chen, Q., Murakami, M., Kimura, M., Terada, Y., Kano, M.R., Miyazono, K., Uesaka, M., Nishiyama, N., Kataoka, K.: Accumulation of sub-100 nm polymeric micelles in poorly permeable tumours depends on size. Nat. Nanotechnol. 6(12), 815–823 (2011). https://doi.org/10.1038/nnano.2011.166

    Article  Google Scholar 

  141. Moghimi, S.M., Porter, C.J., Muir, I.S., Illum, L., Davis, S.S.: Non-phagocytic uptake of intravenously injected microspheres in rat spleen: influence of particle size and hydrophilic coating. Biochem. Biophys. Res. Commun. 177(2), 861–866 (1991)

    Article  Google Scholar 

  142. Tenzer, S., Docter, D., Kuharev, J., Musyanovych, A., Fetz, V., Hecht, R., Schlenk, F., Fischer, D., Kiouptsi, K., Reinhardt, C., Landfester, K., Schild, H., Maskos, M., Knauer, S.K., Stauber, R.H.: Rapid formation of plasma protein corona critically affects nanoparticle pathophysiology. Nat. Nanotechnol. 8(10), 772–781 (2013). https://doi.org/10.1038/nnano.2013.181

    Article  Google Scholar 

  143. Syed, A., Chan, W.C.: How nanoparticles interact with cancer cells. Cancer Treat. Res. 166, 227–244 (2015). https://doi.org/10.1007/978-3-319-16555-4_10

    Article  Google Scholar 

  144. Gustafson, H.H., Holt-Casper, D., Grainger, D.W., Ghandehari, H.: Nanoparticle uptake: the phagocyte problem. Nano Today. 10(4), 487–510 (2015). https://doi.org/10.1016/j.nantod.2015.06.006

    Article  Google Scholar 

  145. Dobrovolskaia, M.A., McNeil, S.E.: Immunological properties of engineered nanomaterials. Nat. Nanotechnol. 2(8), 469–478 (2007). https://doi.org/10.1038/nnano.2007.223

    Article  Google Scholar 

  146. Cedervall, T., Lynch, I., Foy, M., Berggard, T., Donnelly, S.C., Cagney, G., Linse, S., Dawson, K.A.: Detailed identification of plasma proteins adsorbed on copolymer nanoparticles. Angew. Chem. Int. Ed. Engl. 46(30), 5754–5756 (2007). https://doi.org/10.1002/anie.200700465

    Article  Google Scholar 

  147. Lynch, I., Salvati, A., Dawson, K.A.: Protein-nanoparticle interactions: what does the cell see? Nat. Nanotechnol. 4(9), 546–547 (2009). https://doi.org/10.1038/nnano.2009.248

    Article  Google Scholar 

  148. Nel, A.E., Madler, L., Velegol, D., Xia, T., Hoek, E.M., Somasundaran, P., Klaessig, F., Castranova, V., Thompson, M.: Understanding biophysicochemical interactions at the nano-bio interface. Nat. Mater. 8(7), 543–557 (2009). https://doi.org/10.1038/nmat2442

    Article  Google Scholar 

  149. Cedervall, T., Lynch, I., Lindman, S., Berggard, T., Thulin, E., Nilsson, H., Dawson, K.A., Linse, S.: Understanding the nanoparticle-protein corona using methods to quantify exchange rates and affinities of proteins for nanoparticles. Proc. Natl. Acad. Sci. U. S. A. 104(7), 2050–2055 (2007). https://doi.org/10.1073/pnas.0608582104

    Article  Google Scholar 

  150. Lundqvist, M., Stigler, J., Elia, G., Lynch, I., Cedervall, T., Dawson, K.A.: Nanoparticle size and surface properties determine the protein corona with possible implications for biological impacts. Proc. Natl. Acad. Sci. U. S. A. 105(38), 14265–14270 (2008). https://doi.org/10.1073/pnas.0805135105

    Article  Google Scholar 

  151. Walkey, C.D., Olsen, J.B., Guo, H., Emili, A., Chan, W.C.: Nanoparticle size and surface chemistry determine serum protein adsorption and macrophage uptake. J. Am. Chem. Soc. 134(4), 2139–2147 (2012). https://doi.org/10.1021/ja2084338

    Article  Google Scholar 

  152. Ritz, S., Schottler, S., Kotman, N., Baier, G., Musyanovych, A., Kuharev, J., Landfester, K., Schild, H., Jahn, O., Tenzer, S., Mailander, V.: Protein corona of nanoparticles: distinct proteins regulate the cellular uptake. Biomacromolecules. 16(4), 1311–1321 (2015). https://doi.org/10.1021/acs.biomac.5b00108

    Article  Google Scholar 

  153. Ogawara, K., Furumoto, K., Nagayama, S., Minato, K., Higaki, K., Kai, T., Kimura, T.: Pre-coating with serum albumin reduces receptor-mediated hepatic disposition of polystyrene nanosphere: implications for rational design of nanoparticles. J. Control. Release. 100(3), 451–455 (2004). https://doi.org/10.1016/j.jconrel.2004.07.028

    Article  Google Scholar 

  154. Monopoli, M.P., Aberg, C., Salvati, A., Dawson, K.A.: Biomolecular coronas provide the biological identity of nanosized materials. Nat. Nanotechnol. 7(12), 779–786 (2012). https://doi.org/10.1038/nnano.2012.207

    Article  Google Scholar 

  155. Salvador-Morales, C., Zhang, L., Langer, R., Farokhzad, O.C.: Immunocompatibility properties of lipid-polymer hybrid nanoparticles with heterogeneous surface functional groups. Biomaterials. 30(12), 2231–2240 (2009). https://doi.org/10.1016/j.biomaterials.2009.01.005

    Article  Google Scholar 

  156. Harris, J.M., Chess, R.B.: Effect of pegylation on pharmaceuticals. Nat. Rev. Drug Discov. 2(3), 214–221 (2003). https://doi.org/10.1038/nrd1033

    Article  Google Scholar 

  157. Knop, K., Hoogenboom, R., Fischer, D., Schubert, U.S.: Poly(ethylene glycol) in drug delivery: pros and cons as well as potential alternatives. Angew. Chem. Int. Ed. Engl. 49(36), 6288–6308 (2010). https://doi.org/10.1002/anie.200902672

    Article  Google Scholar 

  158. Pombo Garcia, K., Zarschler, K., Barbaro, L., Barreto, J.A., O'Malley, W., Spiccia, L., Stephan, H., Graham, B.: Zwitterionic-coated “stealth” nanoparticles for biomedical applications: recent advances in countering biomolecular corona formation and uptake by the mononuclear phagocyte system. Small. 10(13), 2516–2529 (2014). https://doi.org/10.1002/smll.201303540

    Article  Google Scholar 

  159. Rodriguez, P.L., Harada, T., Christian, D.A., Pantano, D.A., Tsai, R.K., Discher, D.E.: Minimal “Self” peptides that inhibit phagocytic clearance and enhance delivery of nanoparticles. Science. 339(6122), 971–975 (2013). https://doi.org/10.1126/science.1229568

    Article  Google Scholar 

  160. Parodi, A., Quattrocchi, N., van de Ven, A.L., Chiappini, C., Evangelopoulos, M., Martinez, J.O., Brown, B.S., Khaled, S.Z., Yazdi, I.K., Enzo, M.V., Isenhart, L., Ferrari, M., Tasciotti, E.: Synthetic nanoparticles functionalized with biomimetic leukocyte membranes possess cell-like functions. Nat. Nanotechnol. 8(1), 61–68 (2013). https://doi.org/10.1038/nnano.2012.212

    Article  Google Scholar 

  161. Hu, C.M., Zhang, L., Aryal, S., Cheung, C., Fang, R.H., Zhang, L.: Erythrocyte membrane-camouflaged polymeric nanoparticles as a biomimetic delivery platform. Proc. Natl. Acad. Sci. U. S. A. 108(27), 10980–10985 (2011). https://doi.org/10.1073/pnas.1106634108

    Article  Google Scholar 

  162. Hu, C.M., Fang, R.H., Wang, K.C., Luk, B.T., Thamphiwatana, S., Dehaini, D., Nguyen, P., Angsantikul, P., Wen, C.H., Kroll, A.V., Carpenter, C., Ramesh, M., Qu, V., Patel, S.H., Zhu, J., Shi, W., Hofman, F.M., Chen, T.C., Gao, W., Zhang, K., Chien, S., Zhang, L.: Nanoparticle biointerfacing by platelet membrane cloaking. Nature. 526(7571), 118–121 (2015). https://doi.org/10.1038/nature15373

    Article  Google Scholar 

  163. Ferrari, M.: Frontiers in cancer nanomedicine: directing mass transport through biological barriers. Trends Biotechnol. 28(4), 181–188 (2010). https://doi.org/10.1016/j.tibtech.2009.12.007

    Article  Google Scholar 

  164. Chanan-Khan, A., Szebeni, J., Savay, S., Liebes, L., Rafique, N.M., Alving, C.R., Muggia, F.M.: Complement activation following first exposure to pegylated liposomal doxorubicin (Doxil): possible role in hypersensitivity reactions. Ann. Oncol. 14(9), 1430–1437 (2003)

    Article  Google Scholar 

  165. Schottler, S., Becker, G., Winzen, S., Steinbach, T., Mohr, K., Landfester, K., Mailander, V., Wurm, F.R.: Protein adsorption is required for stealth effect of poly(ethylene glycol)- and poly(phosphoester)-coated nanocarriers. Nat. Nanotechnol. 11(4), 372–377 (2016). https://doi.org/10.1038/nnano.2015.330

    Article  Google Scholar 

  166. Salvati, A., Pitek, A.S., Monopoli, M.P., Prapainop, K., Bombelli, F.B., Hristov, D.R., Kelly, P.M., Aberg, C., Mahon, E., Dawson, K.A.: Transferrin-functionalized nanoparticles lose their targeting capabilities when a biomolecule corona adsorbs on the surface. Nat. Nanotechnol. 8(2), 137–143 (2013). https://doi.org/10.1038/nnano.2012.237

    Article  Google Scholar 

  167. Dong, Y., Love, K.T., Dorkin, J.R., Sirirungruang, S., Zhang, Y., Chen, D., Bogorad, R.L., Yin, H., Chen, Y., Vegas, A.J., Alabi, C.A., Sahay, G., Olejnik, K.T., Wang, W., Schroeder, A., Lytton-Jean, A.K., Siegwart, D.J., Akinc, A., Barnes, C., Barros, S.A., Carioto, M., Fitzgerald, K., Hettinger, J., Kumar, V., Novobrantseva, T.I., Qin, J., Querbes, W., Koteliansky, V., Langer, R., Anderson, D.G.: Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates. Proc. Natl. Acad. Sci. U. S. A. 111(11), 3955–3960 (2014). https://doi.org/10.1073/pnas.1322937111

    Article  Google Scholar 

  168. Sakulkhu, U., Maurizi, L., Mahmoudi, M., Motazacker, M., Vries, M., Gramoun, A., Ollivier Beuzelin, M.G., Vallee, J.P., Rezaee, F., Hofmann, H.: Ex situ evaluation of the composition of protein corona of intravenously injected superparamagnetic nanoparticles in rats. Nanoscale. 6(19), 11439–11450 (2014). https://doi.org/10.1039/c4nr02793k

    Article  Google Scholar 

  169. Walkey, C.D., Olsen, J.B., Song, F., Liu, R., Guo, H., Olsen, D.W., Cohen, Y., Emili, A., Chan, W.C.: Protein corona fingerprinting predicts the cellular interaction of gold and silver nanoparticles. ACS Nano. 8(3), 2439–2455 (2014). https://doi.org/10.1021/nn406018q

    Article  Google Scholar 

  170. Bigdeli, A., Palchetti, S., Pozzi, D., Hormozi-Nezhad, M.R., Baldelli Bombelli, F., Caracciolo, G., Mahmoudi, M.: Exploring cellular interactions of liposomes using protein corona fingerprints and physicochemical properties. ACS Nano. 10(3), 3723–3737 (2016). https://doi.org/10.1021/acsnano.6b00261

    Article  Google Scholar 

  171. Choi, C.H., Zuckerman, J.E., Webster, P., Davis, M.E.: Targeting kidney mesangium by nanoparticles of defined size. Proc. Natl. Acad. Sci. U. S. A. 108(16), 6656–6661 (2011). https://doi.org/10.1073/pnas.1103573108

    Article  Google Scholar 

  172. Zhang, Y.N., Poon, W., Tavares, A.J., McGilvray, I.D., Chan, W.C.: Nanoparticle-liver interactions: cellular uptake and hepatobiliary elimination. J. Control. Release. (2016). https://doi.org/10.1016/j.jconrel.2016.01.020

  173. Decuzzi, P., Godin, B., Tanaka, T., Lee, S.Y., Chiappini, C., Liu, X., Ferrari, M.: Size and shape effects in the biodistribution of intravascularly injected particles. J. Control. Release. 141(3), 320–327 (2010). https://doi.org/10.1016/j.jconrel.2009.10.014

    Article  Google Scholar 

  174. Geng, Y., Dalhaimer, P., Cai, S., Tsai, R., Tewari, M., Minko, T., Discher, D.E.: Shape effects of filaments versus spherical particles in flow and drug delivery. Nat. Nanotechnol. 2(4), 249–255 (2007). https://doi.org/10.1038/nnano.2007.70

    Article  Google Scholar 

  175. Lin, S.Y., Hsu, W.H., Lo, J.M., Tsai, H.C., Hsiue, G.H.: Novel geometry type of nanocarriers mitigated the phagocytosis for drug delivery. J. Control. Release. 154(1), 84–92 (2011). https://doi.org/10.1016/j.jconrel.2011.04.023

    Article  Google Scholar 

  176. Beningo, K.A., Wang, Y.L.: Fc-receptor-mediated phagocytosis is regulated by mechanical properties of the target. J. Cell Sci. 115(Pt 4), 849–856 (2002)

    Article  Google Scholar 

  177. Toy, R., Peiris, P.M., Ghaghada, K.B., Karathanasis, E.: Shaping cancer nanomedicine: the effect of particle shape on the in vivo journey of nanoparticles. Nanomedicine (Lond.). 9(1), 121–134 (2014). https://doi.org/10.2217/nnm.13.191

    Article  Google Scholar 

  178. Ruggiero, A., Villa, C.H., Bander, E., Rey, D.A., Bergkvist, M., Batt, C.A., Manova-Todorova, K., Deen, W.M., Scheinberg, D.A., McDevitt, M.R.: Paradoxical glomerular filtration of carbon nanotubes. Proc. Natl. Acad. Sci. U. S. A. 107(27), 12369–12374 (2010). https://doi.org/10.1073/pnas.0913667107

    Article  Google Scholar 

  179. Lacerda, L., Herrero, M.A., Venner, K., Bianco, A., Prato, M., Kostarelos, K.: Carbon-nanotube shape and individualization critical for renal excretion. Small. 4(8), 1130–1132 (2008). https://doi.org/10.1002/smll.200800323

    Article  Google Scholar 

  180. Liang, X., Wang, H., Zhu, Y., Zhang, R., Cogger, V.C., Liu, X., Xu, Z.P., Grice, J.E., Roberts, M.S.: Short- and long-term tracking of anionic ultrasmall nanoparticles in kidney. ACS Nano. 10(1), 387–395 (2016). https://doi.org/10.1021/acsnano.5b05066

    Article  Google Scholar 

  181. Spill, F., Reynolds, D.S., Kamm, R.D., Zaman, M.H.: Impact of the physical microenvironment on tumor progression and metastasis. Curr. Opin. Biotechnol. 40, 41–48 (2016). https://doi.org/10.1016/j.copbio.2016.02.007

    Article  Google Scholar 

  182. Reisfeld, R.A.: The tumor microenvironment: a target for combination therapy of breast cancer. Crit. Rev. Oncog. 18(1-2), 115–133 (2013)

    Article  Google Scholar 

  183. Wang, L.C., Lo, A., Scholler, J., Sun, J., Majumdar, R.S., Kapoor, V., Antzis, M., Cotner, C.E., Johnson, L.A., Durham, A.C., Solomides, C.C., June, C.H., Pure, E., Albelda, S.M.: Targeting fibroblast activation protein in tumor stroma with chimeric antigen receptor T cells can inhibit tumor growth and augment host immunity without severe toxicity. Cancer Immunol. Res. 2(2), 154–166 (2014). https://doi.org/10.1158/2326-6066.CIR-13-0027

    Article  Google Scholar 

  184. Linton, S.S., Sherwood, S.G., Drews, K.C., Kester, M.: Targeting cancer cells in the tumor microenvironment: opportunities and challenges in combinatorial nanomedicine. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 8(2), 208–222 (2016). https://doi.org/10.1002/wnan.1358

    Article  Google Scholar 

  185. Milane, L., Duan, Z., Amiji, M.: Development of EGFR-targeted polymer blend nanocarriers for combination paclitaxel/lonidamine delivery to treat multi-drug resistance in human breast and ovarian tumor cells. Mol. Pharm. 8(1), 185–203 (2011). https://doi.org/10.1021/mp1002653

    Article  Google Scholar 

  186. Yoo, J.W., Chambers, E., Mitragotri, S.: Factors that control the circulation time of nanoparticles in blood: challenges, solutions and future prospects. Curr. Pharm. Des. 16(21), 2298–2307 (2010)

    Article  Google Scholar 

  187. Padera, T.P., Stoll, B.R., Tooredman, J.B., Capen, D., di Tomaso, E., Jain, R.K.: Pathology: cancer cells compress intratumour vessels. Nature. 427(6976), 695 (2004). https://doi.org/10.1038/427695a

    Article  Google Scholar 

  188. Vaupel, P., Mayer, A.: Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev. 26(2), 225–239 (2007). https://doi.org/10.1007/s10555-007-9055-1

    Article  Google Scholar 

  189. Denison, T.A., Bae, Y.H.: Tumor heterogeneity and its implication for drug delivery. J. Control. Release. 164(2), 187–191 (2012). https://doi.org/10.1016/j.jconrel.2012.04.014

    Article  Google Scholar 

  190. Harris, A.L.: Hypoxia--a key regulatory factor in tumour growth. Nat. Rev. Cancer. 2(1), 38–47 (2002). https://doi.org/10.1038/nrc704

    Article  Google Scholar 

  191. Jain, R.K., Stylianopoulos, T.: Delivering nanomedicine to solid tumors. Nat. Rev. Clin. Oncol. 7(11), 653–664 (2010). https://doi.org/10.1038/nrclinonc.2010.139

    Article  Google Scholar 

  192. Stylianopoulos, T., Poh, M.Z., Insin, N., Bawendi, M.G., Fukumura, D., Munn, L.L., Jain, R.K.: Diffusion of particles in the extracellular matrix: the effect of repulsive electrostatic interactions. Biophys. J. 99(5), 1342–1349 (2010). https://doi.org/10.1016/j.bpj.2010.06.016

    Article  Google Scholar 

  193. Lieleg, O., Baumgartel, R.M., Bausch, A.R.: Selective filtering of particles by the extracellular matrix: an electrostatic bandpass. Biophys. J. 97(6), 1569–1577 (2009). https://doi.org/10.1016/j.bpj.2009.07.009

    Article  Google Scholar 

  194. Boucher, Y., Baxter, L.T., Jain, R.K.: Interstitial pressure gradients in tissue-isolated and subcutaneous tumors: implications for therapy. Cancer Res. 50(15), 4478–4484 (1990)

    Google Scholar 

  195. Polyak, K., Haviv, I., Campbell, I.G.: Co-evolution of tumor cells and their microenvironment. Trends Genet. 25(1), 30–38 (2009). https://doi.org/10.1016/j.tig.2008.10.012

    Article  Google Scholar 

  196. Cabarcas, S.M., Mathews, L.A., Farrar, W.L.: The cancer stem cell niche--there goes the neighborhood? Int. J. Cancer. 129(10), 2315–2327 (2011). https://doi.org/10.1002/ijc.26312

    Article  Google Scholar 

  197. Yameen, B., Choi, W.I., Vilos, C., Swami, A., Shi, J., Farokhzad, O.C.: Insight into nanoparticle cellular uptake and intracellular targeting. J. Control. Release. 190, 485–499 (2014). https://doi.org/10.1016/j.jconrel.2014.06.038

    Article  Google Scholar 

  198. Veiga, E., Cossart, P.: Listeria hijacks the clathrin-dependent endocytic machinery to invade mammalian cells. Nat. Cell Biol. 7(9), 894–900 (2005). https://doi.org/10.1038/ncb1292

    Article  Google Scholar 

  199. Tsuji, T., Yoshitomi, H., Usukura, J.: Endocytic mechanism of transferrin-conjugated nanoparticles and the effects of their size and ligand number on the efficiency of drug delivery. Microscopy (Oxf). 62(3), 341–352 (2013). https://doi.org/10.1093/jmicro/dfs080

    Article  Google Scholar 

  200. Shete, H.K., Prabhu, R.H., Patravale, V.B.: Endosomal escape: a bottleneck in intracellular delivery. J. Nanosci. Nanotechnol. 14(1), 460–474 (2014)

    Article  Google Scholar 

  201. Whitehead, K.A., Langer, R., Anderson, D.G.: Knocking down barriers: advances in siRNA delivery. Nat. Rev. Drug Discov. 8(2), 129–138 (2009)

    Article  Google Scholar 

  202. Schroeder, A., Levins, C.G., Cortez, C., Langer, R., Anderson, D.G.: Lipid-based nanotherapeutics for siRNA delivery. J. Intern. Med. 267(1), 9–21 (2010). https://doi.org/10.1111/j.1365-2796.2009.02189.x

    Article  Google Scholar 

  203. Varkouhi, A.K., Scholte, M., Storm, G., Haisma, H.J.: Endosomal escape pathways for delivery of biologicals. J. Control. Release. 151(3), 220–228. S0168-3659(10)00905-3 (2011). https://doi.org/10.1016/j.jconrel.2010.11.004

    Article  Google Scholar 

  204. Cheng, X., Lee, R.J.: The role of helper lipids in lipid nanoparticles (LNPs) designed for oligonucleotide delivery. Adv. Drug Deliv. Rev. 99 (Pt A). 129–137 (2016). https://doi.org/10.1016/j.addr.2016.01.022

  205. Kauffman, K.J., Webber, M.J., Anderson, D.G.: Materials for non-viral intracellular delivery of messenger RNA therapeutics. J. Control. Release. (2015). https://doi.org/10.1016/j.jconrel.2015.12.032

  206. Gratton, S.E., Ropp, P.A., Pohlhaus, P.D., Luft, J.C., Madden, V.J., Napier, M.E., DeSimone, J.M.: The effect of particle design on cellular internalization pathways. Proc. Natl. Acad. Sci. U. S. A. 105(33), 11613–11618 (2008). https://doi.org/10.1073/pnas.0801763105

    Article  Google Scholar 

  207. Jiang, W., Kim, B.Y., Rutka, J.T., Chan, W.C.: Nanoparticle-mediated cellular response is size-dependent. Nat. Nanotechnol. 3(3), 145–150. nnano.2008.30 (2008). https://doi.org/10.1038/nnano.2008.30

    Article  Google Scholar 

  208. Leserman, L.D., Barbet, J., Kourilsky, F., Weinstein, J.N.: Targeting to cells of fluorescent liposomes covalently coupled with monoclonal antibody or protein A. Nature. 288(5791), 602–604 (1980)

    Article  Google Scholar 

  209. Heath, T.D., Fraley, R.T., Papahdjopoulos, D.: Antibody targeting of liposomes: cell specificity obtained by conjugation of F(ab')2 to vesicle surface. Science. 210(4469), 539–541 (1980)

    Article  Google Scholar 

  210. Torchilin, V.P.: Immunoliposomes and PEGylated immunoliposomes: possible use for targeted delivery of imaging agents. Immunomethods. 4(3), 244–258 (1994)

    Article  Google Scholar 

  211. Kamaly, N., Kalber, T., Thanou, M., Bell, J.D., Miller, A.D.: Folate receptor targeted bimodal liposomes for tumor magnetic resonance imaging. Bioconjug. Chem. 20(4), 648–655 (2009). https://doi.org/10.1021/bc8002259

    Article  Google Scholar 

  212. Gallo, J., Kamaly, N., Lavdas, I., Stevens, E., Nguyen, Q.D., Wylezinska-Arridge, M., Aboagye, E.O., Long, N.J.: CXCR4-targeted and MMP-responsive iron oxide nanoparticles for enhanced magnetic resonance imaging. Angew. Chem. Int. Ed. Engl. 53(36), 9550–9554 (2014). https://doi.org/10.1002/anie.201405442

    Article  Google Scholar 

  213. Kirpotin, D.B., Drummond, D.C., Shao, Y., Shalaby, M.R., Hong, K., Nielsen, U.B., Marks, J.D., Benz, C.C., Park, J.W.: Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. Cancer Res. 66(13), 6732–6740 (2006). https://doi.org/10.1158/0008-5472.CAN-05-4199

    Article  Google Scholar 

  214. Bartlett, D.W., Su, H., Hildebrandt, I.J., Weber, W.A., Davis, M.E.: Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc. Natl. Acad. Sci. U. S. A. 104(39), 15549–15554 (2007). https://doi.org/10.1073/pnas.0707461104

    Article  Google Scholar 

  215. Teesalu, T., Sugahara, K.N., Ruoslahti, E.: Tumor-penetrating peptides. Front. Oncol. 3, 216 (2013). https://doi.org/10.3389/fonc.2013.00216

    Article  Google Scholar 

  216. Matsumura, Y., Gotoh, M., Muro, K., Yamada, Y., Shirao, K., Shimada, Y., Okuwa, M., Matsumoto, S., Miyata, Y., Ohkura, H., Chin, K., Baba, S., Yamao, T., Kannami, A., Takamatsu, Y., Ito, K., Takahashi, K.: Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer. Ann. Oncol. 15(3), 517–525 (2004)

    Article  Google Scholar 

  217. Mamot, C., Ritschard, R., Wicki, A., Stehle, G., Dieterle, T., Bubendorf, L., Hilker, C., Deuster, S., Herrmann, R., Rochlitz, C.: Tolerability, safety, pharmacokinetics, and efficacy of doxorubicin-loaded anti-EGFR immunoliposomes in advanced solid tumours: a phase 1 dose-escalation study. Lancet Oncol. 13(12), 1234–1241 (2012). https://doi.org/10.1016/S1470-2045(12)70476-X

    Article  Google Scholar 

  218. http://clinicaltrials.gov/ct2/show/NCT00470613. Accessed 11 Oct 2017

  219. Sankhala, K.K., Mita, A.C., Adinin, R., Wood, L., Beeram, M., Bullock, S., Yamagata, N., Matsuno, K., Fujisawa, T., Phan, A.: A phase I pharmacokinetic (PK) study of MBP-426, a novel liposome encapsulated oxaliplatin. J. Clin. Oncol. 27(Abstract no: 2535), 15S (2009)

    Google Scholar 

  220. Geretti, E., Leonard, S.C., Dumont, N., Lee, H., Zheng, J., De Souza, R., Gaddy, D.F., Espelin, C.W., Jaffray, D.A., Moyo, V., Nielsen, U.B., Wickham, T.J., Hendriks, B.S.: Cyclophosphamide-mediated tumor priming for enhanced delivery and antitumor activity of HER2-targeted liposomal doxorubicin (MM-302). Mol. Cancer Ther. 14(9), 2060–2071 (2015). https://doi.org/10.1158/1535-7163.MCT-15-0314

    Article  Google Scholar 

  221. Cheng, Z., Al Zaki, A., Hui, J.Z., Muzykantov, V.R., Tsourkas, A.: Multifunctional nanoparticles: cost versus benefit of adding targeting and imaging capabilities. Science. 338(6109), 903–910 (2012). https://doi.org/10.1126/science.1226338

    Article  Google Scholar 

  222. https://clinicaltrials.gov/ct2/show/NCT01812746. Accessed 11 Oct 2017

  223. Heidel, J.D., Liu, J.Y., Yen, Y., Zhou, B., Heale, B.S., Rossi, J.J., Bartlett, D.W., Davis, M.E.: Potent siRNA inhibitors of ribonucleotide reductase subunit RRM2 reduce cell proliferation in vitro and in vivo. Clin. Cancer Res. 13(7), 2207–2215 (2007). https://doi.org/10.1158/1078-0432.CCR-06-2218

    Article  Google Scholar 

  224. Bareford, L.M., Swaan, P.W.: Endocytic mechanisms for targeted drug delivery. Adv. Drug Deliv. Rev. 59(8), 748–758 (2007)

    Article  Google Scholar 

  225. Seibel, P., Trappe, J., Villani, G., Klopstock, T., Papa, S., Reichmann, H.: Transfection of mitochondria: strategy towards a gene therapy of mitochondrial DNA diseases. Nucleic Acids Res. 23(1), 10–17 (1995)

    Article  Google Scholar 

  226. Weissig, V., Torchilin, V.P.: Cationic bolasomes with delocalized charge centers as mitochondria-specific DNA delivery systems. Adv. Drug Deliv. Rev. 49(1-2), 127–149 (2001)

    Article  Google Scholar 

  227. Longley, D.B., Johnston, P.G.: Molecular mechanisms of drug resistance. J. Pathol. 205(2), 275–292 (2005). https://doi.org/10.1002/path.1706

    Article  Google Scholar 

  228. Abdullah, L.N., Chow, E.K.: Mechanisms of chemoresistance in cancer stem cells. Clin. Transl. Med. 2(1), 3 (2013). https://doi.org/10.1186/2001-1326-2-3

    Article  Google Scholar 

  229. Chow, E.K.-H., L-l, F., Chen, X., Bishop, J.M.: Oncogene-specific formation of chemoresistant murine hepatic cancer stem cells. Hepatology (Baltimore, Md). 56(4), 1331–1341 (2012). https://doi.org/10.1002/hep.25776

    Article  Google Scholar 

  230. Chow, E.K., Ho, D.: Cancer nanomedicine: from drug delivery to imaging. Sci. Transl. Med. 5(216), 216rv214 (2013). https://doi.org/10.1126/scitranslmed.3005872

    Article  Google Scholar 

  231. Tardi, P.G., Dos Santos, N., Harasym TO, Johnstone, S.A., Zisman, N., Tsang, A.W., Bermudes, D.G., Mayer, L.D.: Drug ratio-dependent antitumor activity of irinotecan and cisplatin combinations in vitro and in vivo. Mol. Cancer Ther. 8(8), 2266–2275 (2009). https://doi.org/10.1158/1535-7163.MCT-09-0243

    Article  Google Scholar 

  232. Zhang, Y.F., Wang, J.C., Bian, D.Y., Zhang, X., Zhang, Q.: Targeted delivery of RGD-modified liposomes encapsulating both combretastatin A-4 and doxorubicin for tumor therapy: in vitro and in vivo studies. Eur. J. Pharm. Biopharm. 74(3), 467–473 (2010). https://doi.org/10.1016/j.ejpb.2010.01.002

    Article  Google Scholar 

  233. Yang, Y., Hu, Y., Wang, Y., Li, J., Liu, F., Huang, L.: Nanoparticle delivery of pooled siRNA for effective treatment of non-small cell lung cancer. Mol. Pharm. 9(8), 2280–2289 (2012). https://doi.org/10.1021/mp300152v

    Article  Google Scholar 

  234. Lv, S., Tang, Z., Li, M., Lin, J., Song, W., Liu, H., Huang, Y., Zhang, Y., Chen, X.: Co-delivery of doxorubicin and paclitaxel by PEG-polypeptide nanovehicle for the treatment of non-small cell lung cancer. Biomaterials. 35(23), 6118–6129 (2014). https://doi.org/10.1016/j.biomaterials.2014.04.034

    Article  Google Scholar 

  235. Duan, X., Xiao, J., Yin, Q., Zhang, Z., Yu, H., Mao, S., Li, Y.: Smart pH-sensitive and temporal-controlled polymeric micelles for effective combination therapy of doxorubicin and disulfiram. ACS Nano. 7(7), 5858–5869 (2013). https://doi.org/10.1021/nn4010796

    Article  Google Scholar 

  236. Tang, S., Yin, Q., Su, J., Sun, H., Meng, Q., Chen, Y., Chen, L., Huang, Y., Gu, W., Xu, M., Yu, H., Zhang, Z., Li, Y.: Inhibition of metastasis and growth of breast cancer by pH-sensitive poly (beta-amino ester) nanoparticles co-delivering two siRNA and paclitaxel. Biomaterials. 48, 1–15 (2015). https://doi.org/10.1016/j.biomaterials.2015.01.049

    Article  Google Scholar 

  237. Guan, S., Rosenecker, J.: Nanotechnologies in delivery of mRNA therapeutics using nonviral vector-based delivery systems. Gene Ther. 24(3), 133–143 (2017). https://doi.org/10.1038/gt.2017.5

    Article  Google Scholar 

  238. Liu, C., Zhang, L., Liu, H., Cheng, K.: Delivery strategies of the CRISPR-Cas9 gene-editing system for therapeutic applications. J. Control. Release. 266, 17–26 (2017). https://doi.org/10.1016/j.jconrel.2017.09.012

    Article  Google Scholar 

  239. Juliano, R.L.: The delivery of therapeutic oligonucleotides. Nucleic Acids Res. 44(14), 6518–6548 (2016). https://doi.org/10.1093/nar/gkw236

    Article  Google Scholar 

  240. Bramsen, J.B., Kjems, J.: Development of therapeutic-grade small interfering RNAs by chemical engineering. Front. Genet. 3, 154 (2012). https://doi.org/10.3389/fgene.2012.00154

    Article  Google Scholar 

  241. Barve, M., Wang, Z., Kumar, P., Jay, C.M., Luo, X., Bedell, C., Mennel, R.G., Wallraven, G., Brunicardi, F.C., Senzer, N., Nemunaitis, J., Rao, D.D.: Phase 1 Trial of Bi-shRNA STMN1 BIV in Refractory Cancer. Mol. Ther. 23(6), 1123–1130 (2015). https://doi.org/10.1038/mt.2015.14

    Article  Google Scholar 

  242. Beg, M.S., Brenner, A.J., Sachdev, J., Borad, M., Kang, Y.K., Stoudemire, J., Smith, S., Bader, A.G., Kim, S., Hong, D.S.: Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors. Invest. New Drugs. 35(2), 180–188 (2017). https://doi.org/10.1007/s10637-016-0407-y

    Article  Google Scholar 

  243. Beg, M.S., Brenner, A.J., Sachdev, J., Borad, M., Kang, Y.K., Stoudemire, J., Smith, S., Bader, A.G., Kim, S., Hong, D.S.: Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors. Invest. New Drugs. 35(2), 180-188 (2017). https://doi.org/10.1007/s10637-016-0407-y

  244. van Zandwijk, N., Pavlakis, N., Kao, S.C., Linton, A., Boyer, M.J., Clarke, S., Huynh, Y., Chrzanowska, A., Fulham, M.J., Bailey, D.L., Cooper, W.A., Kritharides, L., Ridley, L., Pattison, S.T., MacDiarmid, J., Brahmbhatt, H., Reid, G.: Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study. Lancet Oncol. 18(10), 1386–1396 (2017). https://doi.org/10.1016/S1470-2045(17)30621-6

    Article  Google Scholar 

  245. Wagner, M.J., Mitra, R., McArthur, M.J., Baze, W., Barnhart, K., Wu, S.Y., Rodriguez-Aguayo, C., Zhang, X., Coleman, R.L., Lopez-Berestein, G., Sood, A.K.: Preclinical Mammalian Safety Studies of EPHARNA (DOPC Nanoliposomal EphA2-Targeted siRNA). Mol. Cancer Ther. 16(6), 1114–1123 (2017). https://doi.org/10.1158/1535-7163.MCT-16-0541

    Article  Google Scholar 

  246. Santel, A., Aleku, M., Keil, O., Endruschat, J., Esche, V., Fisch, G., Dames, S., Loffler, K., Fechtner, M., Arnold, W., Giese, K., Klippel, A., Kaufmann, J.: A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium. Gene Ther. 13(16), 1222–1234 (2006). https://doi.org/10.1038/sj.gt.3302777

    Article  Google Scholar 

  247. Gilleron, J., Querbes, W., Zeigerer, A., Borodovsky, A., Marsico, G., Schubert, U., Manygoats, K., Seifert, S., Andree, C., Stoter, M., Epstein-Barash, H., Zhang, L., Koteliansky, V., Fitzgerald, K., Fava, E., Bickle, M., Kalaidzidis, Y., Akinc, A., Maier, M., Zerial, M.: Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape. Nat. Biotechnol. 31(7), 638–646 (2013). https://doi.org/10.1038/nbt.2612

    Article  Google Scholar 

  248. Sahay, G., Querbes, W., Alabi, C., Eltoukhy, A., Sarkar, S., Zurenko, C., Karagiannis, E., Love, K., Chen, D., Zoncu, R., Buganim, Y., Schroeder, A., Langer, R., Anderson, D.G.: Efficiency of siRNA delivery by lipid nanoparticles is limited by endocytic recycling. Nat. Biotechnol. 31(7), 653–658 (2013). https://doi.org/10.1038/nbt.2614

    Article  Google Scholar 

  249. Goldberg, M.S.: Immunoengineering: how nanotechnology can enhance cancer immunotherapy. Cell. 161(2), 201–204 (2015). https://doi.org/10.1016/j.cell.2015.03.037

    Article  Google Scholar 

  250. Rossmann, E., Osterborg, A., Lofvenberg, E., Choudhury, A., Forssmann, U., von Heydebreck, A., Schroder, A., Mellstedt, H.: Mucin 1-specific active cancer immunotherapy with tecemotide (L-BLP25) in patients with multiple myeloma: an exploratory study. Hum. Vaccin. Immunother. 10(11), 3394–3408 (2014). https://doi.org/10.4161/hv.29918

    Article  Google Scholar 

  251. Samuel, J., Budzynski, W.A., Reddish, M.A., Ding, L., Zimmermann, G.L., Krantz, M.J., Koganty, R.R., Longenecker, B.M.: Immunogenicity and antitumor activity of a liposomal MUC1 peptide-based vaccine. Int. J. Cancer. 75(2), 295–302 (1998)

    Article  Google Scholar 

  252. Butts, C., Socinski, M.A., Mitchell, P.L., Thatcher, N., Havel, L., Krzakowski, M., Nawrocki, S., Ciuleanu, T.E., Bosquee, L., Trigo, J.M., Spira, A., Tremblay, L., Nyman, J., Ramlau, R., Wickart-Johansson, G., Ellis, P., Gladkov, O., Pereira, J.R., Eberhardt, W.E., Helwig, C., Schroder, A., Shepherd, F.A., St, t.: Tecemotide (L-BLP25) versus placebo after chemoradiotherapy for stage III non-small-cell lung cancer (START): a randomised, double-blind, phase 3 trial. Lancet Oncol. 15(1), 59–68 (2014). https://doi.org/10.1016/S1470-2045(13)70510-2

    Article  Google Scholar 

  253. Thomas, A., Giaccone, G.: Why has active immunotherapy not worked in lung cancer? Ann. Oncol. 26(11), 2213–2220 (2015). https://doi.org/10.1093/annonc/mdv323

    Article  Google Scholar 

  254. Hamilton, E., Blackwell, K., Hobeika, A.C., Clay, T.M., Broadwater, G., Ren, X.R., Chen, W., Castro, H., Lehmann, F., Spector, N., Wei, J., Osada, T., Lyerly, H.K., Morse, M.A.: Phase 1 clinical trial of HER2-specific immunotherapy with concomitant HER2 kinase inhibition [corrected]. J. Transl. Med. 10, 28 (2012). https://doi.org/10.1186/1479-5876-10-28

    Article  Google Scholar 

  255. Kager, L., Potschger, U., Bielack, S.: Review of mifamurtide in the treatment of patients with osteosarcoma. Ther. Clin. Risk Manag. 6, 279–286 (2010)

    Article  Google Scholar 

  256. Libutti, S.K., Paciotti, G.F., Byrnes, A.A., Alexander Jr., H.R., Gannon, W.E., Walker, M., Seidel, G.D., Yuldasheva, N., Tamarkin, L.: Phase I and pharmacokinetic studies of CYT-6091, a novel PEGylated colloidal gold-rhTNF nanomedicine. Clin. Cancer Res. 16(24), 6139–6149 (2010). https://doi.org/10.1158/1078-0432.CCR-10-0978

    Article  Google Scholar 

  257. Min, Y., Caster, J.M., Eblan, M.J., Wang, A.Z.: Clinical translation of nanomedicine. Chem. Rev. (2015). https://doi.org/10.1021/acs.chemrev.5b00116

  258. Mura, S., Couvreur, P.: Nanotheranostics for personalized medicine. Adv. Drug Deliv. Rev. 64(13), 1394–1416 (2012). https://doi.org/10.1016/j.addr.2012.06.006

    Article  Google Scholar 

  259. Tyner, K.M., Zou, P., Yang, X., Zhang, H., Cruz, C.N., Lee, S.L.: Product quality for nanomaterials: current U.S. experience and perspective. Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 7(5), 640–654 (2015). https://doi.org/10.1002/wnan.1338

    Article  Google Scholar 

  260. Farokhzad, O.C.: Nanotechnology for drug delivery: the perfect partnership. Expert Opin. Drug Deliv. 5(9), 927–929 (2008). https://doi.org/10.1517/17425247.5.9.927

    Article  Google Scholar 

  261. Goldberg, M.S., Hook, S.S., Wang, A.Z., Bulte, J.W.M., Patri, A.K., Uckun, F.M., Cryns, V.L., Hanes, J., Akin, D., Hall, J.B., Gharkholo, N., Mumper, R.J.: Biotargeted nanomedicines for cancer: six tenets before you begin. Nanomedicine (Lond.). 8(2), 299–308 (2013). https://doi.org/10.2217/nnm.13.3

    Article  Google Scholar 

Download references

Acknowledgment

N.K. acknowledges support from the Lundbeck Foundation, Denmark.

Author information

Authors and Affiliations

  1. David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Department of Chemical Engineering, Cambridge, MA, USA

    Bomy Lee Chung & Robert Langer

  2. Technical University of Denmark. Department of Micro and Nanotechnology, DTU Nanotech, Lyngby, Denmark

    Joseph Kaplinsky & Nazila Kamaly

Authors
  1. Bomy Lee Chung
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joseph Kaplinsky
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert Langer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nazila Kamaly
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nazila Kamaly .

Editor information

Editors and Affiliations

  1. Department of Chemical Engineering, University of Massachusetts Lowell, Lowell, MA, USA

    Prakash Rai

  2. National Cancer Institute, NIH Nanodelivery Systems and Devices Branch Cancer Imaging Program, Division of Cancer Treatment and Diagnosis, Rockville, MD, USA

    Stephanie A. Morris

Rights and permissions

Reprints and permissions

Copyright information

© 2019 This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chung, B.L., Kaplinsky, J., Langer, R., Kamaly, N. (2019). Delivery of Cancer Nanotherapeutics. In: Rai, P., Morris, S.A. (eds) Nanotheranostics for Cancer Applications. Bioanalysis, vol 5. Springer, Cham. https://doi.org/10.1007/978-3-030-01775-0_8

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-01775-0_8

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-01773-6

  • Online ISBN: 978-3-030-01775-0

  • eBook Packages: EngineeringEngineering (R0)

Publish with us

Policies and ethics

Search

Navigation