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Multifunctional Polymeric Nano-Carriers in Targeted Drug Delivery

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Targeted Drug Delivery : Concepts and Design

Part of the book series: Advances in Delivery Science and Technology ((ADST))

Abstract

“The quest to achieve big shifted the focus of scientific community to small” seems to be quite strange to hear, but emergence of nanotechnology in the field of drug delivery made this wonder true. A meticulous look toward the evolution of nanotechnology clearly accentuates that the field has marched at a phenomenal pace with the emergence of nanoparticles like a “magic bullet.” Step-by-step engineering of the nanoparticles resulted in the development of multifunctional pharmaceutical nano-carriers combining multiple useful properties in single particle providing the theragnostic approach with improved safety and efficacy. This chapter elucidates in detail the concept of multifunctionality of polymeric nano-carriers for treatment of disease conditions particularly cancer. The chapter also covers the recent advances surrounding the multifunctionality of polymeric nanoparticles for improved therapeutic outcomes.

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Abbreviations

ADPA:

Anthracene-9, 10-dipropionic acid, disodium salt

ASGP:

Asialoglycoprotein

BBB:

Blood–brain barrier

BMP:

Bone morphogenetic protein

CDs:

Cyclodextrins

CH:

Chitosan

CLSM:

Confocal laser scanning microscopy

CNS:

Central nervous system

COX:

Cyclo oxygenase

DNA:

Deoxy nucleic acid

DOX:

Doxorubicin

EC:

Ethyl cellulose

ECMs:

Extracellular matrices

EGF:

Epidermal growth factor

EGFP:

Expressing green fluorescent protein

EGFR:

Epidermal growth factor receptor

EPR:

Enhanced permeability and retention effect

FA:

Folic acid

FDA:

Food and Drug Administration

FGF:

Fibroblast growth factor

FTIC:

Fluorescein isothiocyanate

GA:

Glycyrrhizinic acid

GL:

Glycyrrhizin

HA:

Hyaluronan

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

HER2:

Human epidermal growth factor receptor 2

HPMC:

Hydroxypropylmethylcellulose

mAb:

Monoclonal antibodies

MC:

Methyl cellulose

MDR:

Multidrug resistance

MEND:

Multifunctional envelope-type nano-device

MMPNs:

multifunctional magneto-polymeric nanohybrids

MPAP:

Myristoylated polyarginine peptides

MRI:

Magnetic Resonance Imaging

mRNA:

messenger RNA

NiMOS:

Nanoparticles-in-microsphere oral system

NIRF:

Near-infrared fluorescent dye

NPs:

Nanoparticles

PAA:

Polyacrylic cid

PBLA:

Poly (β-benzyl l-aspartate)

PCL:

Polycaprolactone

pDNA:

Plasmid deoxyribonucleic acid

PEG:

Polyethylene glycol

PEI:

Polyethylenimine

P-gp:

P-glycoprotein

PLA:

Poly lactic acid

PLGA:

(poly(lactic-co-glycolic) acid)

PLL:

Poly (l-lysine)

PS:

Polystyrene

PSS:

Poly(styrenesulfonate)

PTX:

Paclitaxel

QD:

Quantum dots

RBITC:

Rhodamine B isothiocyanate

RES:

Reticuloendothelial system

RGD:

Arginine–glycine–aspartic acid

RNA:

Ribo nucleic acid

scAbPSCA:

Single chain prostate stem cell antigen antibodies

scFv:

Single-chain fragment variables

siRNAs:

Small interfering RNA

SPECT:

Single-photon emission computed tomography

SPIONs:

Superparamagnetic iron oxide nanoparticles

TfRs:

Transferrin receptors

TPGS:

d-α-tocopheryl polyethylene glycol succinate

VEGF:

Vascular endothelial growth factor

WGA:

Wheat germ agglutinin

γ-PGA:

γ-polyglutamic acid

References

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

    CAS  PubMed  Google Scholar 

  2. Singh R, Lillard JW Jr (2009) Nanoparticle-based targeted drug delivery. Exp Mol Pathol 86:215–223. doi:10.1016/j.yexmp.2008.12.004

    CAS  PubMed Central  PubMed  Google Scholar 

  3. Agrawal AK, Harde H, Thanki K, Jain S (2013) Improved stability and antidiabetic potential of insulin containing folic acid functionalized polymer stabilized multilayered liposomes following oral administration. Biomacromolecules 15:350–360. doi:10.1021/bm401580k

    PubMed  Google Scholar 

  4. Jain S, Indulkar A, Harde H, Agrawal AK (2014) Oral mucosal immunization using glucomannosylated bilosomes. J Biomed Nanotechnol 10:932–947. doi:10.1166/jbn.2014.1800

    CAS  PubMed  Google Scholar 

  5. Jain S, Harde H, Indulkar A, Agrawal AK (2013) Improved stability and immunological potential of tetanus toxoid containing surface engineered bilosomes following oral administration. Nanomed Nanotechnol Biol Med 10:431–440. doi:10.1016/j.nano.2013.08.012

    Google Scholar 

  6. Jain S, Sharma JM, Agrawal AK, Mahajan RR (2013) Surface stabilized efavirenz nanoparticles for oral bioavailability enhancement. J Biomed Nanotechnol 9:1862–1874. doi:10.1166/jbn.2013.1683

    CAS  PubMed  Google Scholar 

  7. Harde H, Agrawal AK, Jain S (2014) Development of stabilized glucomannosylated chitosan nanoparticles using tandem crosslinking method for oral vaccine delivery. Nanomedicine (Lond), 1–19. doi:10.2217/nnm.13.225

    Google Scholar 

  8. Agrawal A, Gupta P, Khanna A, Sharma R, Chandrabanshi H, Gupta N, Patil U, Yadav S (2010) Development and characterization of in situ gel system for nasal insulin delivery. Pharmazie 65:188–193. doi:10.1691/ph.2010.9188

    CAS  PubMed  Google Scholar 

  9. Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE (2001) Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release 70:1–20. doi:10.1016/S0168-3659(00)00339-4

    CAS  PubMed  Google Scholar 

  10. Sanvicens N, Marco MP (2008) Multifunctional nanoparticles–properties and prospects for their use in human medicine. Trends Biotechnol 26:425–433. doi:10.1016/j.tibtech.2008.04.005

    CAS  PubMed  Google Scholar 

  11. Pillai O, Panchagnula R (2001) Polymers in drug delivery. Curr Opin Chem Biol 5:447–451. doi:10.1016/S1367-5931(00)00227-1

    CAS  PubMed  Google Scholar 

  12. Lee KY, Mooney DJ (2012) Alginate: properties and biomedical applications. Prog Polym Sci 37:106–126. doi:10.1016/j.progpolymsci.2011.06.003

    CAS  PubMed Central  PubMed  Google Scholar 

  13. Sun G, Shen YI, Ho CC, Kusuma S, Gerecht S (2010) Functional groups affect physical and biological properties of dextran‐based hydrogels. J Biomed Mater Res A 93:1080–1090. doi:10.1002/jbm.a.32604

    PubMed  Google Scholar 

  14. Serefoglou E, Oberdisse J, Staikos G (2007) Characterization of the soluble nanoparticles formed through coulombic interaction of bovine serum albumin with anionic graft copolymers at low pH. Biomacromolecules 8:1195–1199. doi:10.1021/bm061094t

    CAS  PubMed  Google Scholar 

  15. Chopra S, Mahdi S, Kaur J, Iqbal Z, Talegaonkar S, Ahmad FJ (2006) Advances and potential applications of chitosan derivatives as mucoadhesive biomaterials in modern drug delivery. J Pharm Pharmacol 58:1021–1032. doi:10.1211/jpp.58.8.0002

    CAS  PubMed  Google Scholar 

  16. Yin L, Ding J, He C, Cui L, Tang C, Yin C (2009) Drug permeability and mucoadhesion properties of thiolated trimethyl chitosan nanoparticles in oral insulin delivery. Biomaterials 30:5691–5700. doi:10.1016/j.biomaterials.2009.06.055

    CAS  PubMed  Google Scholar 

  17. Agrawal AK, Das M, Jain S (2012) In situ gel systems as ‘smart’ carriers for sustained ocular drug delivery. Expert Opin Drug Deliv 9:383–402. doi:10.1517/17425247.2012.665367

    CAS  PubMed  Google Scholar 

  18. Choudhary H, Agrawal A, Malviya R, Yadav S, Jaliwala Y, Patil U (2010) Evaluation and optimization of preparative variables for controlled-release floating microspheres of levodopa/carbidopa. Pharmazie 65:194–198. doi:10.1691/ph.2010.9288

    CAS  PubMed  Google Scholar 

  19. Kopeček J, Ulbrich K (1983) Biodegradation of biomedical polymers. Prog Polym Sci 9:1–58

    Google Scholar 

  20. Panyam J, Labhasetwar V (2003) Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 55:329–347. doi:10.1016/S0169-409X(02)00228-4

    CAS  PubMed  Google Scholar 

  21. Wu K-J, Wu C-S, Chang J-S (2007) Biodegradability and mechanical properties of polycaprolactone composites encapsulating phosphate-solubilizing bacterium Bacillus sp. PG01. Process Biochem 42:669–675

    Google Scholar 

  22. Richard A, Margaritis A (2001) Poly (glutamic acid) for biomedical applications. Crit Rev Biotechnol 21:219–232. doi:10.1080/07388550108984171

    CAS  PubMed  Google Scholar 

  23. Jain S, Patil SR, Swarnakar NK, Agrawal AK (2012) Oral delivery of doxorubicin using novel polyelectrolyte-stabilized liposomes (layersomes). Mol Pharm 9:2626–2635. doi:10.1021/mp300202c

    CAS  PubMed  Google Scholar 

  24. Brannon-Peppas L, Blanchette JO (2012) Nanoparticle and targeted systems for cancer therapy. Adv Drug Deliv Rev 64:206–212. doi:10.1016/j.addr.2012.09.033

    Google Scholar 

  25. Brigger I, Dubernet C, Couvreur P (2002) Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev 54:631–651. doi:10.1016/S0169-409X(02)00044-3

    CAS  PubMed  Google Scholar 

  26. Das M, Mishra D, Maiti T, Basak A, Pramanik P (2008) Bio-functionalization of magnetite nanoparticles using an aminophosphonic acid coupling agent: new, ultradispersed, iron-oxide folate nanoconjugates for cancer-specific targeting. Nanotechnology 19:415101. doi:10.1088/0957-4484/19/41/415101

    PubMed  Google Scholar 

  27. Cascante M, Centelles JJ, Veech RL, Lee W-NP, Boros LG (2000) Role of thiamin (vitamin B-1) and transketolase in tumor cell proliferation. Nutr Cancer 36:150–154. doi:10.1207/S15327914NC3602_2

    CAS  PubMed  Google Scholar 

  28. Park JW, Benz CC, Martin FJ (2004) Future directions of liposome-and immunoliposome-based cancer therapeutics. Semin Oncol 31(6 Suppl 13):196–205

    CAS  PubMed  Google Scholar 

  29. Kumari A, Yadav SK, Yadav SC (2010) Biodegradable polymeric nanoparticles based drug delivery systems. Colloids Surf B: Biointerfaces 75:1–18. doi:10.1016/j.colsurfb.2009.09.001

    CAS  PubMed  Google Scholar 

  30. Jain AK, Das M, Swarnakar NK, Jain S (2011) Engineered PLGA nanoparticles: an emerging delivery tool in cancer therapeutics. Crit Rev Ther Durg 28:1–45. doi:10.1615/CritRevTherDrugCarrierSyst.v28.i1.10

    CAS  Google Scholar 

  31. Shenoy D, Little S, Langer R, Amiji M (2005) Poly (ethylene oxide)-modified poly (β-amino ester) nanoparticles as a pH-sensitive system for tumor-targeted delivery of hydrophobic drugs: part 2. In vivo distribution and tumor localization studies. Pharm Res 22:2107–2114

    CAS  PubMed Central  PubMed  Google Scholar 

  32. Uhrich KE, Cannizzaro SM, Langer RS, Shakesheff KM (1999) Polymeric systems for controlled drug release. Chem Rev 99:3181–3198. doi:10.1021/cr940351u

    CAS  PubMed  Google Scholar 

  33. Farokhzad OC, Cheng J, Teply BA, Sherifi I, Jon S, Kantoff PW, Richie JP, Langer R (2006) Targeted nanoparticle-aptamer bioconjugates for cancer chemotherapy in vivo. Proc Natl Acad Sci U S A 103:6315–6320. doi:10.1073/pnas.0601755103

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Antony A (1992) The biological chemistry of folate receptors. Blood 79:2807–2820

    CAS  PubMed  Google Scholar 

  35. Vidal JM, Koulibaly M, Jost JL, Duron JJ, Chigot JP, Vayre P, Aurengo A, Legrand JC, Rosselin G, Gespach C (1998) Differential transferrin receptor density in human colorectal cancer: a potential probe for diagnosis and therapy. Int J Oncol 13:871–875. doi:10.3892/ijo.13.4.871

  36. Rusch V, Klimstra D, Venkatraman E, Pisters PW, Langenfeld J, Dmitrovsky E (1997) Overexpression of the epidermal growth factor receptor and its ligand transforming growth factor alpha is frequent in resectable non-small cell lung cancer but does not predict tumor progression. Clin Cancer Res 3:515–522

    CAS  PubMed  Google Scholar 

  37. Korc M, Chandrasekar B, Yamanaka Y, Friess H, Buchier M, Beger HG (1992) Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha. J Clin Invest 90:1352–1360. doi:10.1172/jci116001

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Carvalho I, Milanezi F, Martins A, Reis RM, Schmitt F (2005) Overexpression of platelet-derived growth factor receptor alpha in breast cancer is associated with tumour progression. Breast Cancer Res 7:R788–R795. doi:10.1186/bcr1304

    CAS  PubMed Central  PubMed  Google Scholar 

  39. Lewis GD, Lofgren JA, McMurtrey AE, Nuijens A, Fendly BM, Bauer KD, Sliwkowski MX (1996) Growth regulation of human breast and ovarian tumor cells by heregulin: evidence for the requirement of ErbB2 as a critical component in mediating heregulin responsiveness. Cancer Res 56:1457–1465

    CAS  PubMed  Google Scholar 

  40. Dorsam RT, Gutkind JS (2007) G-protein-coupled receptors and cancer. Nat Rev Cancer 7:79–94. doi:10.1038/nrc2069

    CAS  PubMed  Google Scholar 

  41. Rozengurt E, Guha S, Sinnett-Smith J (2002) Gastrointestinal peptide signalling in health and disease. Eur J Surg 587:23–38

    Google Scholar 

  42. Szepeshazi K, Schally AV, Nagy A, Halmos G (2005) Inhibition of growth of experimental human and hamster pancreatic cancers in vivo by a targeted cytotoxic bombesin analog. Pancreas 31:275–282

    CAS  PubMed  Google Scholar 

  43. Liu G, Duranteau L, Carel J-C, Monroe J, Doyle DA, Shenker A (1999) Leydig-cell tumors caused by an activating mutation of the gene encoding the luteinizing hormone receptor. N Engl J Med 341:1731–1736. doi:10.1056/NEJM199912023412304

    CAS  PubMed  Google Scholar 

  44. Parma J, Duprez L, Van Sande J, Cochaux P, Gervy C, Mockel J, Dumont J, Vassart G (1993) Somatic mutations in the thyrotropin receptor gene cause hyperfunctioning thyroid adenomas. Nature 365:649–651. doi:10.1038/365649a0

    CAS  PubMed  Google Scholar 

  45. Kukowska-Latallo JF, Candido KA, Cao Z, Nigavekar SS, Majoros IJ, Thomas TP, Balogh LP, Khan MK, Baker JR (2005) Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer. Cancer Res 65:5317–5324. doi:10.1158/0008-5472.CAN-04-3921

    CAS  PubMed  Google Scholar 

  46. Iinuma H, Maruyama K, Okinaga K, Sasaki K, Sekine T, Ishida O, Ogiwara N, Johkura K, Yonemura Y (2002) Intracellular targeting therapy of cisplatin‐encapsulated transferrin‐polyethylene glycol liposome on peritoneal dissemination of gastric cancer. Int J Cancer 99:130–137. doi:10.1002/ijc.10242

    CAS  PubMed  Google Scholar 

  47. Ishida O, Maruyama K, Tanahashi H, Iwatsuru M, Sasaki K, Eriguchi M, Yanagie H (2001) Liposomes bearing polyethyleneglycol-coupled transferrin with intracellular targeting property to the solid tumors in vivo. Pharm Res 18:1042–1048. doi:10.1023/A:1010960900254

    CAS  PubMed  Google Scholar 

  48. Ekblom P, Thesleff I, Lehto VP, Virtanen I (1983) Distribution of the transferrin receptor in normal human fibroblasts and fibrosarcoma cells. Int J Cancer 31:111–117. doi:10.1002/ijc.2910310118

    CAS  PubMed  Google Scholar 

  49. Li J, Ji J, Holmes LM, Burgin KE, Barton LB, Yu X, Wagner TE, Wei Y (2004) Fusion protein from RGD peptide and Fc fragment of mouse immunoglobulin G inhibits angiogenesis in tumor. Cancer Gene Ther 11:363–370. doi:10.1038/sj.cgt.7700707

    CAS  PubMed  Google Scholar 

  50. Ruoslahti E (1994) Cell adhesion and tumor metastasis. Princess Takamatsu Symp 24:99–105

    CAS  PubMed  Google Scholar 

  51. Peer D, Margalit R (2004) Tumor-targeted hyaluronan nanoliposomes increase the antitumor activity of liposomal doxorubicin in syngeneic and human xenograft mouse tumor models. Neoplasia 6(4):343–353, doi:10.1593/neo.03460

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Hu Z, Sun Y, Garen A (1999) Targeting tumor vasculature endothelial cells and tumor cells for immunotherapy of human melanoma in a mouse xenograft model. Proc Natl Acad Sci U S A 96:8161–8166. doi:10.1073/pnas.96.14.8161

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Upadhyay KK, Le Meins JF, Misra A, Voisin P, Bouchaud V, Ibarboure E, Schatz C, Lecommandoux S (2009) Biomimetic doxorubicin loaded polymersomes from hyaluronan-block-poly(gamma-benzyl glutamate) copolymers. Biomacromolecules 10:2802–2808. doi:10.1021/bm9006419

    CAS  PubMed  Google Scholar 

  54. Upadhyay KK, Bhatt AN, Mishra AK, Dwarakanath BS, Jain S, Schatz C, Le Meins JF, Farooque A, Chandraiah G, Jain AK, Misra A, Lecommandoux S (2010) The intracellular drug delivery and anti tumor activity of doxorubicin loaded poly(gamma-benzyl L-glutamate)-b-hyaluronan polymersomes. Biomaterials 31:2882–2892. doi:10.1016/j.biomaterials.2009.12.043

    CAS  PubMed  Google Scholar 

  55. Upadhyay KK, Mishra AK, Chuttani K, Kaul A, Schatz C, Le Meins JF, Misra A, Lecommandoux S (2012) The in vivo behavior and antitumor activity of doxorubicin-loaded poly(gamma-benzyl l-glutamate)-block-hyaluronan polymersomes in Ehrlich ascites tumor-bearing BalB/c mice. Nanomedicine 8:71–80. doi:10.1016/j.nano.2011.05.008

    CAS  PubMed  Google Scholar 

  56. Upadhyay KK, Bhatt AN, Castro E, Mishra AK, Chuttani K, Dwarakanath BS, Schatz C, Le Meins JF, Misra A, Lecommandoux S (2010) In vitro and in vivo evaluation of docetaxel loaded biodegradable polymersomes. Macromol Biosci 10:503–512. doi:10.1002/mabi.200900415

    CAS  PubMed  Google Scholar 

  57. Pang Z, Gao H, Yu Y, Guo L, Chen J, Pan S, Ren J, Wen Z, Jiang X (2011) Enhanced intracellular delivery and chemotherapy for glioma rats by transferrin-conjugated biodegradable polymersomes loaded with doxorubicin. Bioconjug Chem 22:1171–1180. doi:10.1021/bc200062q

    CAS  PubMed  Google Scholar 

  58. Gabizon AA (2001) Pegylated liposomal doxorubicin: metamorphosis of an old drug into a new form of chemotherapy. Cancer Invest 19:424–436

    CAS  PubMed  Google Scholar 

  59. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, Langer R (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2:751–760. doi:10.1038/nnano.2007.387

    CAS  PubMed  Google Scholar 

  60. Goldenberg MM (1999) Trastuzumab, a recombinant DNA-derived humanized monoclonal antibody, a novel agent for the treatment of metastatic breast cancer. Clin Ther 21:309–318. doi:10.1016/S0149-2918(00)88288-0

    CAS  PubMed  Google Scholar 

  61. Martiny-Baron G, Marmé D (1995) VEGF-mediated tumour angiogenesis: a new target for cancer therapy. Curr Opin Biotechnol 6:675–680. doi:10.1016/0958-1669(95)80111-1

    CAS  PubMed  Google Scholar 

  62. Allen TM (2002) Ligand-targeted therapeutics in anticancer therapy. Nat Rev Cancer 2:750–763. doi:10.1038/nrc903

    CAS  PubMed  Google Scholar 

  63. Carter P (2001) Improving the efficacy of antibody-based cancer therapies. Nat Rev Cancer 1:118–129. doi:10.1038/35101072

    CAS  PubMed  Google Scholar 

  64. Arnold DM, Dentali F, Crowther MA, Meyer RM, Cook RJ, Sigouin C, Fraser GA, Lim W, Kelton JG (2007) Systematic review: efficacy and safety of rituximab for adults with idiopathic thrombocytopenic purpura. Ann Intern Med 146:25–33. doi:10.7326/0003-4819-146-1-200701020-00006

    PubMed  Google Scholar 

  65. Trail P, Willner D, Lasch S, Henderson A, Hofstead S, Casazza A, Firestone R, Hellstrom I, Hellstrom K (1993) Cure of xenografted human carcinomas by BR96-doxorubicin immunoconjugates. Science 261:212–215. doi:10.1126/science.8327892

    CAS  PubMed  Google Scholar 

  66. Tolcher AW, Sugarman S, Gelmon KA, Cohen R, Saleh M, Isaacs C, Young L, Healey D, Onetto N, Slichenmyer W (1999) Randomized phase II study of BR96-doxorubicin conjugate in patients with metastatic breast cancer. J Clin Oncol 17:478–478

    CAS  PubMed  Google Scholar 

  67. White RR, Sullenger BA, Rusconi CP (2000) Developing aptamers into therapeutics. J Clin Invest 106:929–934. doi:10.1172/JCI11325

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Debets MF, Leenders WP, Verrijp K, Zonjee M, Meeuwissen SA, Otte‐Höller I, van Hest J (2013) Nanobody‐functionalized polymersomes for tumor‐vessel targeting. Macromol Biosci 13:938–945, doi:10.1002/mabi.201300039

    CAS  PubMed  Google Scholar 

  69. Jain RK (2005) Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307:58–62. doi:10.1126/science.1104819

    CAS  PubMed  Google Scholar 

  70. Folkman J (2007) Angiogenesis: an organizing principle for drug discovery? Nat Rev Drug Discov 6:273–286. doi:10.1038/nrd2115

    CAS  PubMed  Google Scholar 

  71. Yang JC, Haworth L, Sherry RM, Hwu P, Schwartzentruber DJ, Topalian SL, Steinberg SM, Chen HX, Rosenberg SA (2003) A randomized trial of bevacizumab, an anti–vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349:427–434. doi:10.1056/NEJMoa021491

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Cobleigh MA, Langmuir VK, Sledge GW, Miller KD, Haney L, Novotny WF, Reimann JD, Vassel A (2003) A phase I/II dose-escalation trial of bevacizumab in previously treated metastatic breast cancer. Semin Oncol 30(5 Suppl 16):117–124

    CAS  PubMed  Google Scholar 

  73. Mayer RJ (2004) Two steps forward in the treatment of colorectal cancer. N Engl J Med 350:2406–2408. doi:10.1056/NEJMe048098

    CAS  PubMed  Google Scholar 

  74. Emanuel S, Gruninger RH, Fuentes-Pesquera A, Connolly PJ, Seamon JA, Hazel S, Tominovich R, Hollister B, Napier C, D’Andrea MR (2004) A vascular endothelial growth factor receptor-2 kinase inhibitor potentiates the activity of the conventional chemotherapeutic agents paclitaxel and doxorubicin in tumor xenograft models. Mol Pharmacol 66:635–647. doi:10.1124/mol.104.000638

    CAS  PubMed  Google Scholar 

  75. Ma L, Francia G, Viloria-Petit A, Hicklin DJ, du Manoir J, Rak J, Kerbel RS (2005) In vitro procoagulant activity induced in endothelial cells by chemotherapy and antiangiogenic drug combinations: modulation by lower-dose chemotherapy. Cancer Res 65:5365–5373. doi:10.1158/0008-5472.CAN-04-3156

    CAS  PubMed  Google Scholar 

  76. Tuettenberg J, Grobholz R, Korn T, Wenz F, Erber R, Vajkoczy P (2005) Continuous low-dose chemotherapy plus inhibition of cyclooxygenase-2 as an antiangiogenic therapy of glioblastoma multiforme. J Cancer Res Clin Oncol 131:31–40. doi:10.1007/s00432-004-0620-5

    CAS  PubMed  Google Scholar 

  77. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342. doi:10.1056/NEJMoa032691

    CAS  PubMed  Google Scholar 

  78. Kabbinavar FF, Hambleton J, Mass RD, Hurwitz HI, Bergsland E, Sarkar S (2005) Combined analysis of efficacy: the addition of bevacizumab to fluorouracil/leucovorin improves survival for patients with metastatic colorectal cancer. J Clin Oncol 23:3706–3712. doi:10.1200/JCO.2005.00.232

    CAS  PubMed  Google Scholar 

  79. McCarthy M (2003) Antiangiogenesis drug promising for metastatic colorectal cancer. Lancet 361:1959. doi:10.1016/S0140-6736(03)13603-3

    PubMed  Google Scholar 

  80. Sengupta S, Eavarone D, Capila I, Zhao G, Watson N, Kiziltepe T, Sasisekharan R (2005) Temporal targeting of tumour cells and neovasculature with a nanoscale delivery system. Nature 436:568–572. doi:10.1038/nature03794

    CAS  PubMed  Google Scholar 

  81. Donnenberg VS, Donnenberg AD (2005) Multiple drug resistance in cancer revisited: the cancer stem cell hypothesis. J Clin Pharmacol 45:872–877. doi:10.1177/0091270005276905

    CAS  PubMed  Google Scholar 

  82. Bradley G, Juranka PF, Ling V (1988) Mechanism of multidrug resistance. BBA-Rev Cancer 948:87–128. doi:10.1016/0304-419X(88)90006-6

    CAS  Google Scholar 

  83. Harris AL, Hochhauser D (1992) Mechanisms of multidrug resistance in cancer treatment. Acta Oncol 31:205–213. doi:10.3109/02841869209088904

    CAS  PubMed  Google Scholar 

  84. Hayes JD, Pulford DJ (1995) The glut athione S-transferase supergene family: regulation of GST and the contribution of the lsoenzymes to cancer chemoprotection and drug resistance part I. Crit Rev Biochem Mol Biol 30:445–520. doi:10.3109/10409239509083491

    CAS  PubMed  Google Scholar 

  85. Adams J, Cory S (2007) The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 26:1324–1337. doi:10.1038/sj.onc.1210220

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Ferreira C, Tolis C, Giaccone G (1999) p53 and chemosensitivity. Ann Oncol 10:1011–1021. doi:10.1023/A:1008361818480

    CAS  PubMed  Google Scholar 

  87. Gottesman MM, Fojo T, Bates SE (2002) Multidrug resistance in cancer: role of ATP–dependent transporters. Nat Rev Cancer 2:48–58. doi:10.1038/nrc706

    CAS  PubMed  Google Scholar 

  88. Takara K, Sakaeda T, Okumura K (2006) An update on overcoming MDR1-mediated multidrug resistance in cancer chemotherapy. Curr Pharm Des 12:273–286. doi:10.2174/138161206775201965

    CAS  PubMed  Google Scholar 

  89. Ferry D, Traunecker H, Kerr D (1996) Clinical trials of P-glycoprotein reversal in solid tumours. Eur J Cancer 32:1070–1081. doi:10.1016/0959-8049(96)00091-3

    Google Scholar 

  90. Oh KT, Baik HJ, Lee AH, Oh YT, Youn YS, Lee ES (2009) The reversal of drug-resistance in tumors using a drug-carrying nanoparticular system. Int J Mol Sci 10:3776–3792. doi:10.3390/ijms10093776

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Palmeira A, Sousa E, Vasconcelos MH, Pinto MM (2012) Three decades of P-gp inhibitors: skimming through several generations and scaffolds. Curr Med Chem 19:1946–2025. doi:10.2174/092986712800167392

    CAS  PubMed  Google Scholar 

  92. Davis ME, Shin DM (2008) Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov 7:771–782. doi:10.1038/nrd2614

    CAS  PubMed  Google Scholar 

  93. Emilienne Soma C, Dubernet C, Bentolila D, Benita S, Couvreur P (2000) Reversion of multidrug resistance by co-encapsulation of doxorubicin and cyclosporin A in polyalkylcyanoacrylate nanoparticles. Biomaterials 21:1–7. doi:10.1016/S0142-9612(99)00125-8

    Google Scholar 

  94. Patil Y, Sadhukha T, Ma L, Panyam J (2009) Nanoparticle-mediated simultaneous and targeted delivery of paclitaxel and tariquidar overcomes tumor drug resistance. J Control Release 136:21–29. doi:10.1016/j.jconrel.2009.01.021

    CAS  PubMed  Google Scholar 

  95. Hughes CS, Vaden SL, Manaugh CA, Price GS, Hudson L (1998) Modulation of doxorubicin concentration by cyclosporin A in brain and testicular barrier tissues expressing P-glycoprotein in rats. J Neurooncol 37:45–54. doi:10.1023/A:1005900908540

    CAS  PubMed  Google Scholar 

  96. Erlichman C, Moore M, Thiessen JJ, Kerr IG, Walker S, Goodman P, Bjarnason G, DeAngelis C, Bunting P (1993) Phase I pharmacokinetic study of cyclosporin A combined with doxorubicin. Cancer Res 53:4837–4842

    CAS  PubMed  Google Scholar 

  97. Kim JS, Rieter WJ, Taylor KM, An H, Lin W, Lin W (2007) Self-assembled hybrid nanoparticles for cancer-specific multimodal imaging. J Am Chem Soc 129:8962–8963. doi:10.1021/ja073062z

    CAS  PubMed Central  PubMed  Google Scholar 

  98. Rieter WJ, Kim JS, Taylor KM, An H, Lin W, Tarrant T, Lin W (2007) Hybrid silica nanoparticles for multimodal imaging. Angew Chem Int Ed 46:3680–3682. doi:10.1002/anie.200604738

    CAS  Google Scholar 

  99. Lee JH, Yw J, Yeon SI, Shin JS, Cheon J (2006) Dual‐mode nanoparticle probes for high‐performance magnetic resonance and fluorescence imaging of neuroblastoma. Angew Chem 118:8340–8342. doi:10.1002/anie.200603052

    Google Scholar 

  100. Bridot J-L, Faure A-C, Laurent S, Riviere C, Billotey C, Hiba B, Janier M, Josserand V, Coll J-L, Vander Elst L (2007) Hybrid gadolinium oxide nanoparticles: multimodal contrast agents for in vivo imaging. J Am Chem Soc 129:5076–5084. doi:10.1021/ja068356j

    CAS  PubMed  Google Scholar 

  101. Santra S, Bagwe RP, Dutta D, Stanley JT, Walter GA, Tan W, Moudgil BM, Mericle RA (2005) Synthesis and characterization of fluorescent, radio‐opaque, and paramagnetic silica nanoparticles for multimodal bioimaging applications. Adv Mater 17:2165–2169. doi:10.1002/adma.200500018

    CAS  Google Scholar 

  102. Kim J, Lee JE, Lee J, Jang Y, Kim SW, An K, Yu JH, Hyeon T (2006) Generalized fabrication of multifunctional nanoparticle assemblies on silica spheres. Angew Chem 118:4907–4911. doi:10.1002/anie.200504107

    Google Scholar 

  103. Medarova Z, Pham W, Farrar C, Petkova V, Moore A (2007) In vivo imaging of siRNA delivery and silencing in tumors. Nat Med 13:372–377. doi:10.1038/nm1486

    CAS  PubMed  Google Scholar 

  104. Nasongkla N, Bey E, Ren J, Ai H, Khemtong C, Guthi JS, Chin S-F, Sherry AD, Boothman DA, Gao J (2006) Multifunctional polymeric micelles as cancer-targeted, MRI-ultrasensitive drug delivery systems. Nano Lett 6:2427–2430. doi:10.1021/nl061412u

    CAS  PubMed  Google Scholar 

  105. Pourtau L, Oliveira H, Thevenot J, Wan Y, Brisson AR, Sandre O, Miraux S, Thiaudiere E, Lecommandoux S (2013) Antibody‐functionalized magnetic polymersomes: in vivo targeting and imaging of bone metastases using high resolution MRI. Adv Healthc Mater 2:1420–1424. doi:10.1002/adhm.201300061

    CAS  PubMed  Google Scholar 

  106. Yang J, Lee CH, Ko HJ, Suh JS, Yoon HG, Lee K, Huh YM, Haam S (2007) Multifunctional magneto‐polymeric nanohybrids for targeted detection and synergistic therapeutic effects on breast cancer. Angew Chem Int Ed 46:8836–8839. doi:10.1002/anie.200703554

    CAS  Google Scholar 

  107. Kim J, Lee JE, Lee SH, Yu JH, Lee JH, Park TG, Hyeon T (2008) Designed fabrication of a multifunctional polymer nanomedical platform for simultaneous cancer‐targeted imaging and magnetically guided drug delivery. Adv Mater 20:478–483. doi:10.1002/adma.200701726

    CAS  Google Scholar 

  108. Kim K, Kim JH, Park H, Kim Y-S, Park K, Nam H, Lee S, Park JH, Park R-W, Kim I-S (2010) Tumor-homing multifunctional nanoparticles for cancer theragnosis: simultaneous diagnosis, drug delivery, and therapeutic monitoring. J Control Release 146:219–227. doi:10.1016/j.jconrel.2010.04.004

    CAS  PubMed  Google Scholar 

  109. van Vlerken LE, Duan Z, Little SR, Seiden MV, Amiji MM (2008) Biodistribution and pharmacokinetic analysis of paclitaxel and ceramide administered in multifunctional polymer-blend nanoparticles in drug resistant breast cancer model. Mol Pharm 5:516–526. doi:10.1021/mp800030k

    PubMed Central  PubMed  Google Scholar 

  110. Park H, Yang J, Lee J, Haam S, Choi I-H, Yoo K-H (2009) Multifunctional nanoparticles for combined doxorubicin and photothermal treatments. ACS Nano 3:2919–2926. doi:10.1021/nn900215k

    CAS  PubMed  Google Scholar 

  111. Cheng J, Teply BA, Sherifi I, Sung J, Luther G, Gu FX, Levy-Nissenbaum E, Radovic-Moreno AF, Langer R, Farokhzad OC (2007) Formulation of functionalized PLGA–PEG nanoparticles for in vivo targeted drug delivery. Biomaterials 28:869–876. doi:10.1016/j.biomaterials.2006.09.047

    CAS  PubMed Central  PubMed  Google Scholar 

  112. Sun B, Ranganathan B, Feng S-S (2008) Multifunctional poly (d, l-lactide-co-glycolide)/montmorillonite (PLGA/MMT) nanoparticles decorated by Trastuzumab for targeted chemotherapy of breast cancer. Biomaterials 29:475–486. doi:10.1016/j.biomaterials.2007.09.038

    PubMed  Google Scholar 

  113. Sun B, Feng S-S (2009) Trastuzumab-functionalized nanoparticles of biodegradable copolymers for targeted delivery of docetaxel. Nanomedicine (Lond) 4:431–445. doi:10.2217/nnm.09.17

    CAS  Google Scholar 

  114. Danhier F, Vroman B, Lecouturier N, Crokart N, Pourcelle V, Freichels H, Jérôme C, Marchand-Brynaert J, Feron O, Préat V (2009) Targeting of tumor endothelium by RGD-grafted PLGA-nanoparticles loaded with paclitaxel. J Control Release 140:166–173. doi:10.1016/j.jconrel.2009.08.011

    CAS  PubMed  Google Scholar 

  115. Patil YB, Toti US, Khdair A, Ma L, Panyam J (2009) Single-step surface functionalization of polymeric nanoparticles for targeted drug delivery. Biomaterials 30:859–866. doi:10.1016/j.biomaterials.2008.09.056

    CAS  PubMed Central  PubMed  Google Scholar 

  116. Shi D, Cho HS, Chen Y, Xu H, Gu H, Lian J, Wang W, Liu G, Huth C, Wang L (2009) Fluorescent polystyrene–Fe3O4 composite nanospheres for in vivo imaging and hyperthermia. Adv Mater 21:2170–2173. doi:10.1002/adma.200803159

    CAS  Google Scholar 

  117. Schleich N, Sibret P, Danhier P, Ucakar B, Laurent S, Muller R, Jérôme C, Gallez B, Préat V, Danhier F (2013) Dual anticancer drug/superparamagnetic iron oxide-loaded PLGA-based nanoparticles for cancer therapy and magnetic resonance imaging. Int J Pharm 447:94–101. doi:10.1016/j.ijpharm.2013.02.042

    CAS  PubMed  Google Scholar 

  118. Kopelman R, Lee Koo Y-E, Philbert M, Moffat BA, Ramachandra Reddy G, McConville P, Hall DE, Chenevert TL, Bhojani MS, Buck SM (2005) Multifunctional nanoparticle platforms for in vivo MRI enhancement and photodynamic therapy of a rat brain cancer. J Magn Magn Mater 293:404–410. doi:10.1016/j.jmmm.2005.02.061

    CAS  Google Scholar 

  119. Reddy GR, Bhojani MS, McConville P, Moody J, Moffat BA, Hall DE, Kim G, Koo Y-EL, Woolliscroft MJ, Sugai JV (2006) Vascular targeted nanoparticles for imaging and treatment of brain tumors. Clin Cancer Res 12:6677–6686. doi:10.1158/1078-0432.CCR-06-0946

    CAS  PubMed  Google Scholar 

  120. Chatterjee DK, Zhang Y (2007) Multi-functional nanoparticles for cancer therapy. Sci Technol Adv Mater 8:131–133. doi:10.1016/j.stam.2006.09.008

    CAS  Google Scholar 

  121. Pan J, Liu Y, Feng S-S (2010) Multifunctional nanoparticles of biodegradable copolymer blend for cancer diagnosis and treatment. Nanomedicine 5:347–360. doi:10.2217/nnm.10.13

    CAS  PubMed  Google Scholar 

  122. Yang X, Grailer JJ, Rowland IJ, Javadi A, Hurley SA, Steeber DA, Gong S (2010) Multifunctional SPIO/DOX-loaded wormlike polymer vesicles for cancer therapy and MR imaging. Biomaterials 31:9065–9073. doi:10.1016/j.biomaterials.2010.08.039

    CAS  PubMed  Google Scholar 

  123. Maeng JH, Lee D-H, Jung KH, Bae Y-H, Park I-S, Jeong S, Jeon Y-S, Shim C-K, Kim W, Kim J (2010) Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer. Biomaterials 31:4995–5006. doi:10.1016/j.biomaterials.2010.02.068

    CAS  PubMed  Google Scholar 

  124. Ling Y, Wei K, Luo Y, Gao X, Zhong S (2011) Dual docetaxel/superparamagnetic iron oxide loaded nanoparticles for both targeting magnetic resonance imaging and cancer therapy. Biomaterials 32:7139–7150. doi:10.1016/j.biomaterials.2011.05.089

    CAS  PubMed  Google Scholar 

  125. Cheng F-Y, Su C-H, Wu P-C, Yeh C-S (2010) Multifunctional polymeric nanoparticles for combined chemotherapeutic and near-infrared photothermal cancer therapy in vitro and in vivo. Chem Commun 46:3167–3169. doi:10.1039/b919172k

    CAS  Google Scholar 

  126. Cho H-S, Dong Z, Pauletti GM, Zhang J, Xu H, Gu H, Wang L, Ewing RC, Huth C, Wang F (2010) Fluorescent, superparamagnetic nanospheres for drug storage, targeting, and imaging: a multifunctional nanocarrier system for cancer diagnosis and treatment. ACS Nano 4:5398–5404. doi:10.1021/nn101000e

    CAS  PubMed  Google Scholar 

  127. Guo R, Zhang L, Qian H, Li R, Jiang X, Liu B (2010) Multifunctional nanocarriers for cell imaging, drug delivery, and near-IR photothermal therapy. Langmuir 26:5428–5434. doi:10.1021/la903893n

    CAS  PubMed  Google Scholar 

  128. Tuszynski MH, Thal L, Pay M, Salmon DP, Bakay R, Patel P, Blesch A, Vahlsing HL, Ho G, Tong G (2005) A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease. Nat Med 11:551–555. doi:10.1038/nm1239

    CAS  PubMed  Google Scholar 

  129. Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA, Bland RJ, Young D, Strybing K, Eidelberg D (2007) Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson’s disease: an open label, phase I trial. Lancet 369:2097–2105. doi:10.1016/S0140-6736(07)60982-9

    CAS  PubMed  Google Scholar 

  130. Morille M, Passirani C, Vonarbourg A, Clavreul A, Benoit J-P (2008) Progress in developing cationic vectors for non-viral systemic gene therapy against cancer. Biomaterials 29:3477–3496. doi:10.1016/j.biomaterials.2008.04.036

    CAS  PubMed  Google Scholar 

  131. Reischl D, Zimmer A (2009) Drug delivery of siRNA therapeutics: potentials and limits of nanosystems. Nanomed Nanotechnol Biol Med 5:8–20. doi:10.1016/j.nano.2008.06.001

    CAS  Google Scholar 

  132. Roy I, Stachowiak MK, Bergey EJ (2008) Nonviral gene transfection nanoparticles: function and applications in the brain. Nanomed Nanotechnol Biol Med 4:89–97. doi:10.1016/j.nano.2008.01.002

    CAS  Google Scholar 

  133. Jain S, Kumar S, Agrawal AK, Thanki K, Banerjee UC (2013) Enhanced transfection efficiency and reduced cytotoxicity of novel lipid–polymer hybrid nanoplexes. Mol Pharm 10:2416–2425. doi:10.1021/mp400036w

    CAS  PubMed  Google Scholar 

  134. Glover DJ, Lipps HJ, Jans DA (2005) Towards safe, non-viral therapeutic gene expression in humans. Nat Rev Genet 6:299–310. doi:10.1038/nrg1577

    CAS  PubMed  Google Scholar 

  135. Schmidt-Wolf GD, Schmidt-Wolf IG (2003) Non-viral and hybrid vectors in human gene therapy: an update. Trends Mol Med 9:67–72. doi:10.1016/S1471-4914(03)00005-4

    CAS  PubMed  Google Scholar 

  136. Pack DW, Hoffman AS, Pun S, Stayton PS (2005) Design and development of polymers for gene delivery. Nat Rev Drug Discov 4:581–593. doi:10.1038/nrd1775

    CAS  PubMed  Google Scholar 

  137. Lin E-H, Chang H-Y, Yeh S-D, Yang K-Y, Hu H-S, Wu C-W (2013) Polyethyleneimine and DNA nanoparticles-based gene therapy for acute lung injury. Nanomed Nanotechnol Biol Med 9:1293–1303. doi:10.1016/j.nano.2013.05.004

    CAS  Google Scholar 

  138. Vijayanathan V, Thomas T, Thomas TJ (2002) DNA nanoparticles and development of DNA delivery vehicles for gene therapy. Biochemistry 41:14085–14094. doi:10.1021/bi0203987

    CAS  PubMed  Google Scholar 

  139. Kim HO, Kim E, An Y, Choi J, Jang E, Choi EB, Kukreja A, Kim MH, Kang B, Kim DJ (2013) A biodegradable polymersome containing Bcl‐xL siRNA and doxorubicin as a dual delivery vehicle for a synergistic anticancer effect. Macromol Biosci 13:745–754. doi:10.1002/mabi.201200448

    CAS  PubMed  Google Scholar 

  140. Kim Y, Tewari M, Pajerowski JD, Cai S, Sen S, Williams J, Sirsi S, Lutz G, Discher DE (2009) Polymersome delivery of siRNA and antisense oligonucleotides. J Control Release 134:132–140. doi:10.1016/j.jconrel.2008.10.020

    CAS  PubMed Central  PubMed  Google Scholar 

  141. Kommareddy S, Amiji M (2005) Preparation and evaluation of thiol-modified gelatin nanoparticles for intracellular DNA delivery in response to glutathione. Bioconjug Chem 16:1423–1432. doi:10.1021/bc050146t

    CAS  PubMed  Google Scholar 

  142. Kommareddy S, Amiji M (2007) Antiangiogenic gene therapy with systemically administered sFlt-1 plasmid DNA in engineered gelatin-based nanovectors. Cancer Gene Ther 14:488–498. doi:10.1038/sj.cgt.7701041

    CAS  PubMed  Google Scholar 

  143. Pangburn TO, Georgiou K, Bates FS, Kokkoli E (2012) Targeted polymersome delivery of siRNA induces cell death of breast cancer cells dependent upon Orai3 protein expression. Langmuir 28:12816–12830. doi:10.1021/la300874z

    CAS  PubMed  Google Scholar 

  144. Bhavsar MD, Amiji MM (2007) Gastrointestinal distribution and in vivo gene transfection studies with nanoparticles-in-microsphere oral system (NiMOS). J Control Release 119:339–348. doi:10.1016/j.jconrel.2007.03.006

    CAS  PubMed  Google Scholar 

  145. Zhang J, Sun H, Ma PX (2010) Host− guest interaction mediated polymeric assemblies: multifunctional nanoparticles for drug and gene delivery. ACS Nano 4:1049–1059. doi:10.1021/nn901213a

    CAS  PubMed Central  PubMed  Google Scholar 

  146. Davis ME (2009) The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic. Mol Pharm 6:659–668. doi:10.1021/mp900015y

    CAS  PubMed  Google Scholar 

  147. Bellocq NC, Pun SH, Jensen GS, Davis ME (2003) Transferrin-containing, cyclodextrin polymer-based particles for tumor-targeted gene delivery. Bioconjug Chem 14:1122–1132. doi:10.1021/bc034125f

    CAS  PubMed  Google Scholar 

  148. Khalil I, Kogure K, Futaki S, Hama S, Akita H, Ueno M, Kishida H, Kudoh M, Mishina Y, Kataoka K (2007) Octaarginine-modified multifunctional envelope-type nanoparticles for gene delivery. Gene Ther 14:682–689. doi:10.1038/sj.gt.3302910

    CAS  PubMed Central  PubMed  Google Scholar 

  149. Kogure K, Akita H, Harashima H (2007) Multifunctional envelope-type nano device for non-viral gene delivery: concept and application of Programmed Packaging. J Control Release 122:246–251. doi:10.1016/j.jconrel.2007.06.018

    CAS  PubMed  Google Scholar 

  150. Kogure K, Akita H, Yamada Y, Harashima H (2008) Multifunctional envelope-type nano device (MEND) as a non-viral gene delivery system. Adv Drug Deliv Rev 60:559–571. doi:10.1016/j.addr.2007.10.007

    CAS  PubMed  Google Scholar 

  151. Hatakeyama H, Akita H, Harashima H (2011) A multifunctional envelope type nano device (MEND) for gene delivery to tumours based on the EPR effect: a strategy for overcoming the PEG dilemma. Adv Drug Deliv Rev 63:152–160. doi:10.1016/j.addr.2010.09.001

    CAS  PubMed  Google Scholar 

  152. Nakamura Y, Kogure K, Futaki S, Harashima H (2007) Octaarginine-modified multifunctional envelope-type nano device for siRNA. J Control Release 119:360–367. doi:10.1016/j.jconrel.2007.03.010

    CAS  PubMed  Google Scholar 

  153. Hatakeyama H, Ito E, Akita H, Oishi M, Nagasaki Y, Futaki S, Harashima H (2009) A pH-sensitive fusogenic peptide facilitates endosomal escape and greatly enhances the gene silencing of siRNA-containing nanoparticles in vitro and in vivo. J Control Release 139:127–132. doi:10.1016/j.jconrel.2009.06.008

    CAS  PubMed  Google Scholar 

  154. El-Sayed A, Futaki S, Harashima H (2009) Delivery of macromolecules using arginine-rich cell-penetrating peptides: ways to overcome endosomal entrapment. AAPS J 11:13–22. doi:10.1208/s12248-008-9071-2

    CAS  PubMed Central  PubMed  Google Scholar 

  155. Khalil IA, Hayashi Y, Mizuno R, Harashima H (2011) Octaarginine-and pH sensitive fusogenic peptide-modified nanoparticles for liver gene delivery. J Control Release 156:374–380. doi:10.1016/j.jconrel.2011.08.012

    CAS  PubMed  Google Scholar 

  156. Akita H, Kogure K, Moriguchi R, Nakamura Y, Higashi T, Nakamura T, Serada S, Fujimoto M, Naka T, Futaki S (2010) Nanoparticles for ex vivo siRNA delivery to dendritic cells for cancer vaccines: Programmed endosomal escape and dissociation. J Control Release 143:311–317. doi:10.1016/j.jconrel.2010.01.012

    CAS  PubMed  Google Scholar 

  157. Guo S, Qiao Y, Wang W, He H, Deng L, Xing J, Xu J, Liang X-J, Dong A (2010) Poly (ε-caprolactone)-graft-poly (2-(N, N-dimethylamino) ethyl methacrylate) nanoparticles: pH dependent thermo-sensitive multifunctional carriers for gene and drug delivery. J Mater Chem 20:6935–6941. doi:10.1039/C0JM00506A

    CAS  Google Scholar 

  158. Nishikawa M, Yamauchi M, Morimoto K, Ishida E, Takakura Y, Hashida M (2000) Hepatocyte-targeted in vivo gene expression by intravenous injection of plasmid DNA complexed with synthetic multi-functional gene delivery system. Gene Ther 7:548–555. doi:10.1038/sj.gt.3301140

    CAS  PubMed  Google Scholar 

  159. Schiffelers RM, Ansari A, Xu J, Zhou Q, Tang Q, Storm G, Molema G, Lu PY, Scaria PV, Woodle MC (2004) Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. Nucleic Acids Res 32:e149–e149. doi:10.1093/nar/gnh140

    PubMed Central  PubMed  Google Scholar 

  160. Suk JS, Suh J, Choy K, Lai SK, Fu J, Hanes J (2006) Gene delivery to differentiated neurotypic cells with RGD and HIV Tat peptide functionalized polymeric nanoparticles. Biomaterials 27:5143–5150. doi:10.1016/j.biomaterials.2006.05.013

    CAS  PubMed  Google Scholar 

  161. Magadala P, Amiji M (2008) Epidermal growth factor receptor-targeted gelatin-based engineered nanocarriers for DNA delivery and transfection in human pancreatic cancer cells. AAPS J 10:565–576. doi:10.1208/s12248-008-9065-0

    CAS  PubMed Central  PubMed  Google Scholar 

  162. Saeed AO, Magnusson JP, Moradi E, Soliman M, Wang W, Stolnik S, Thurecht KJ, Howdle SM, Alexander C (2011) Modular construction of multifunctional bioresponsive cell-targeted nanoparticles for gene delivery. Bioconjug Chem 22:156–168. doi:10.1021/bc100149g

    CAS  PubMed  Google Scholar 

  163. Patil YB, Swaminathan SK, Sadhukha T, Ma L, Panyam J (2010) The use of nanoparticle-mediated targeted gene silencing and drug delivery to overcome tumor drug resistance. Biomaterials 31:358–365. doi:10.1016/j.biomaterials.2009.09.048

    CAS  PubMed Central  PubMed  Google Scholar 

  164. Chen G, Chen W, Wu Z, Yuan R, Li H, Gao J, Shuai X (2009) MRI-visible polymeric vector bearing CD3 single chain antibody for gene delivery to T cells for immunosuppression. Biomaterials 30:1962–1970. doi:10.1016/j.biomaterials.2008.12.043

    CAS  PubMed  Google Scholar 

  165. Juillerat-Jeanneret L (2008) The targeted delivery of cancer drugs across the blood–brain barrier: chemical modifications of drugs or drug-nanoparticles? Drug Discov Today 13:1099–1106. doi:10.1016/j.drudis.2008.09.005

    CAS  PubMed  Google Scholar 

  166. Wong HL, Wu XY, Bendayan R (2012) Nanotechnological advances for the delivery of CNS therapeutics. Adv Drug Deliv Rev 64:686–700. doi:10.1016/j.addr.2011.10.007

    CAS  PubMed  Google Scholar 

  167. Kreuter J, Shamenkov D, Petrov V, Ramge P, Cychutek K, Koch-Brandt C, Alyautdin R (2002) Apolipoprotein-mediated transport of nanoparticle-bound drugs across the blood-brain barrier. J Drug Target 10:317–325. doi:10.1080/10611860290031877

    CAS  PubMed  Google Scholar 

  168. Kreuter J, Alyautdin RN, Kharkevich DA, Ivanov AA (1995) Passage of peptides through the blood-brain barrier with colloidal polymer particles (nanoparticles). Brain Res 674:171–174. doi:10.1016/0006-8993(95)00023-J

    CAS  PubMed  Google Scholar 

  169. Gulyaev AE, Gelperina SE, Skidan IN, Antropov AS, Kivman GY, Kreuter J (1999) Significant transport of doxorubicin into the brain with polysorbate 80-coated nanoparticles. Pharm Res 16:1564–1569. doi:10.1023/A:1018983904537

    CAS  PubMed  Google Scholar 

  170. Kreuter J (2012) Nanoparticulate systems for brain delivery of drugs. Adv Drug Deliv Rev 64:213–222. doi:10.1016/S0169-409X(00)00122-8

    Google Scholar 

  171. Alyautdin R, Tezikov E, Ramge P, Kharkevich D, Begley D, Kreuter J (1998) Significant entry of tubocurarine into the brain of rats by adsorption to polysorbate 80-coated polybutylcyanoacrylate nanoparticles: an in situ brain perfusion study. J Microencapsul 15:67–74. doi:10.3109/02652049809006836

    CAS  PubMed  Google Scholar 

  172. Alyautdin RN, Petrov VE, Langer K, Berthold A, Kharkevich DA, Kreuter J (1997) Delivery of loperamide across the blood-brain barrier with polysorbate 80-coated polybutylcyanoacrylate nanoparticles. Pharm Res 14:325–328. doi:10.1023/A:1012098005098

    CAS  PubMed  Google Scholar 

  173. Gelperina S, Smirnova Z, Khalanskiy A, Skidan I, Bobruskin A, Kreuter J. (2000) Chemotherapy of brain tumours using doxorubicin bound to polysorbate 80-coated nanoparticles. In: Proceedings of the 3rd World Meeting APV/APGI, Berlin, 2000, pp. 441–442

    Google Scholar 

  174. Kreuter J, Petrov V, Kharkevich D, Alyautdin R (1997) Influence of the type of surfactant on the analgesic effects induced by the peptide dalargin after its delivery across the blood–brain barrier using surfactant-coated nanoparticles. J Control Release 49:81–87. doi:10.1016/S0168-3659(97)00061-8

    CAS  Google Scholar 

  175. Schröder U, Sabel BA (1996) Nanoparticles, a drug carrier system to pass the blood-brain barrier, permit central analgesic effects of iv dalargin injections. Brain Res 710:121–124. doi:10.1016/0006-8993(95)01375-X

    PubMed  Google Scholar 

  176. Schroeder U, Sommerfeld P, Sabel BA (1998) Efficacy of oral dalargin-loaded nanoparticle delivery across the blood–brain barrier. Peptides 19:777–780. doi:10.1016/S0196-9781(97)00474-9

    CAS  PubMed  Google Scholar 

  177. Schroeder U, Sommerfeld P, Ulrich S, Sabel BA (1998) Nanoparticle technology for delivery of drugs across the blood–brain barrier. J Pharm Sci 87:1305–1307. doi:10.1021/js980084y

    CAS  PubMed  Google Scholar 

  178. Chen Y, Liu L (2012) Modern methods for delivery of drugs across the blood–brain barrier. Adv Drug Deliv Rev 64:640–665. doi:10.1016/j.addr.2011.11.010

    CAS  PubMed  Google Scholar 

  179. Hans M, Lowman A (2002) Biodegradable nanoparticles for drug delivery and targeting. Curr Opin Solid State Mater Sci 6:319–327. doi:10.1016/S1359-0286(02)00117-1

    CAS  Google Scholar 

  180. Wilson B, Samanta MK, Santhi K, Kumar KPS, Paramakrishnan N, Suresh B (2008) Poly (n-butylcyanoacrylate) nanoparticles coated with polysorbate 80 for the targeted delivery of rivastigmine into the brain to treat Alzheimer’s disease. Brain Res 1200:159–168. doi:10.1016/j.brainres.2008.01.039

    CAS  PubMed  Google Scholar 

  181. Liu G, Garrett MR, Men P, Zhu X, Perry G, Smith MA (2005) Nanoparticle and other metal chelation therapeutics in Alzheimer disease. BBA-Mol Basis Dis 1741:246–252. doi:10.1016/j.bbadis.2005.06.006

    CAS  Google Scholar 

  182. Christen Y (2000) Oxidative stress and Alzheimer disease. Am J Clin Nutr 71:621–629

    Google Scholar 

  183. Hazel JR, Eugene Williams E (1990) The role of alterations in membrane lipid composition in enabling physiological adaptation of organisms to their physical environment. Prog Lipid Res 29:167–227

    CAS  PubMed  Google Scholar 

  184. Henderson BW, Dougherty TJ (1992) How does photodynamic therapy work? Photochem Photobiol 55:145–157. doi:10.1111/j.1751-1097.1992.tb04222.x

    CAS  PubMed  Google Scholar 

  185. Tang W, Xu H, Kopelman R, Philbert MA (2005) Photodynamic characterization and in vitro application of methylene blue‐containing nanoparticle platforms. Photochem Photobiol 81:242–249. doi:10.1111/j.1751-1097.2005.tb00181.x

    CAS  PubMed  Google Scholar 

  186. Porkka K, Laakkonen P, Hoffman JA, Bernasconi M, Ruoslahti E (2002) A fragment of the HMGN2 protein homes to the nuclei of tumor cells and tumor endothelial cells in vivo. Proc Natl Acad Sci U S A 99:7444–7449. doi:10.1073/pnas.062189599

    CAS  PubMed Central  PubMed  Google Scholar 

  187. Abels C (2004) Targeting of the vascular system of solid tumours by photodynamic therapy (PDT). Photochem Photobiol Sci 3:765–771. doi:10.1039/b314241h

    CAS  PubMed  Google Scholar 

  188. Tian X-H, Lin X-N, Wei F, Feng W, Huang Z-C, Wang P, Ren L, Diao Y (2011) Enhanced brain targeting of temozolomide in polysorbate-80 coated polybutylcyanoacrylate nanoparticles. Int J Nanomedicine 6:445–452. doi:10.2147/IJN.S16570

    CAS  PubMed Central  PubMed  Google Scholar 

  189. Kuo Y-C, Chen H-H (2006) Effect of nanoparticulate polybutylcyanoacrylate and methylmethacrylate–sulfopropylmethacrylate on the permeability of zidovudine and lamivudine across the in vitro blood–brain barrier. Int J Pharm 327:160–169. doi:10.1016/j.ijpharm.2006.07.044

    CAS  PubMed  Google Scholar 

  190. Roney C, Kulkarni P, Arora V, Antich P, Bonte F, Wu A, Mallikarjuana NN, Manohar S, Liang H-F, Kulkarni AR, Sung H-W, Sairam M, Aminabhavi TM (2005) Targeted nanoparticles for drug delivery through the blood–brain barrier for Alzheimer’s disease. J Control Release 108:193–214. doi:10.1016/j.jconrel.2005.07.024

    CAS  PubMed  Google Scholar 

  191. Calvo P, Gouritin B, Chacun H, Desmaële D, D’Angelo J, Noel J-P, Georgin D, Fattal E, Andreux JP, Couvreur P (2001) Long-circulating PEGylated polycyanoacrylate nanoparticles as new drug carrier for brain delivery. Pharm Res 18:1157–1166. doi:10.1023/A:1010931127745

    CAS  PubMed  Google Scholar 

  192. Gao X, Wu B, Zhang Q, Chen J, Zhu J, Zhang W, Rong Z, Chen H, Jiang X (2007) Brain delivery of vasoactive intestinal peptide enhanced with the nanoparticles conjugated with wheat germ agglutinin following intranasal administration. J Control Release 121:156–167. doi:10.1016/j.jconrel.2007.05.026

    CAS  PubMed  Google Scholar 

  193. Ulbrich K, Hekmatara T, Herbert E, Kreuter J (2009) Transferrin-and transferrin-receptor-antibody-modified nanoparticles enable drug delivery across the blood–brain barrier (BBB). Eur J Pharm Biopharm 71:251–256. doi:10.1016/j.ejpb.2008.08.021

    CAS  PubMed  Google Scholar 

  194. Blumberg BS, London WT (1981) Hepatitis B virus and the prevention of primary hepatocellular carcinoma. N Engl J Med 304:782–784. doi:10.1056/NEJM198103263041312

    CAS  PubMed  Google Scholar 

  195. Mimi CY, Mack T, Hanisch R, Peters RL, Henderson BE, Pike MC (1983) Hepatitis, alcohol consumption, cigarette smoking, and hepatocellular carcinoma in Los Angeles. Cancer Res 43:6077–6079

    Google Scholar 

  196. Ohnishi K, Iida S, Iwama S, Goto N, Nomura F, Takashi M, Mishima A, Kono K, Kimura K, Musha H (1982) The effect of chronic habitual alcohol intake on the development of liver cirrhosis and hepatocellular carcinoma: relation to hepatitis B surface antigen carriage. Cancer 49:672–677. doi:10.1002/1097-0142(19820215)49:4<672::AID-CNCR2820490415>3.0.CO;2-#

    CAS  PubMed  Google Scholar 

  197. Ashwell G, Harford J (1982) Carbohydrate-specific receptors of the liver. Annu Rev Biochem 51:531–554. doi:10.1146/annurev.bi.51.070182.002531

    CAS  PubMed  Google Scholar 

  198. Wu J, Nantz MH, Zern MA (2002) Targeting hepatocytes for drug and gene delivery: emerging novel approaches and applications. Front Biosci 7:d717

    CAS  PubMed  Google Scholar 

  199. Ciechanover A, Schwartz AL, Lodish HF (1983) Sorting and recycling of cell surface receptors and endocytosed ligands: the asialoglycoprotein and transferrin receptors. J Cell Biochem 23:107–130. doi:10.1002/jcb.240230111

    CAS  PubMed  Google Scholar 

  200. Liang H-F, Chen C-T, Chen S-C, Kulkarni AR, Chiu Y-L, Chen M-C, Sung H-W (2006) Paclitaxel-loaded poly (γ-glutamic acid)-poly (lactide) nanoparticles as a targeted drug delivery system for the treatment of liver cancer. Biomaterials 27:2051–2059. doi:10.1016/j.biomaterials.2005.10.027

    CAS  PubMed  Google Scholar 

  201. Cho C, Cho K, Park I, Kim S, Sasagawa T, Uchiyama M, Akaike T (2001) Receptor-mediated delivery of all trans-retinoic acid to hepatocyte using poly (L-lactic acid) nanoparticles coated with galactose-carrying polystyrene. J Control Release 77:7–15. doi:10.1016/S0168-3659(01)00390-X

    CAS  PubMed  Google Scholar 

  202. Jiang H-L, Kwon J-T, Kim E-M, Kim Y-K, Arote R, Jere D, Jeong H-J, Jang M-K, Nah J-W, Xu C-X (2008) Galactosylated poly (ethylene glycol)-chitosan-graft-polyethylenimine as a gene carrier for hepatocyte-targeting. J Control Release 131:150–157. doi:10.1016/j.jconrel.2008.07.029

    CAS  PubMed  Google Scholar 

  203. Wu D-Q, Lu B, Chang C, Chen C-S, Wang T, Zhang Y-Y, Cheng S-X, Jiang X-J, Zhang X-Z, Zhuo R-X (2009) Galactosylated fluorescent labeled micelles as a liver targeting drug carrier. Biomaterials 30:1363–1371. doi:10.1016/j.biomaterials.2008.11.027

    CAS  PubMed  Google Scholar 

  204. Sawamura T, Nakada H, Hazama H, Shiozaki Y, Sameshima Y, Tashiro Y (1984) Hyperasialoglycoproteinemia in patients with chronic liver diseases and/or liver cell carcinoma. Asialoglycoprotein receptor in cirrhosis and liver cell carcinoma. Gastroenterology 87:1217–1221

    CAS  PubMed  Google Scholar 

  205. Tian Q, Zhang C-N, Wang X-H, Wang W, Huang W, Cha R-T, Wang C-H, Yuan Z, Liu M, Wan H-Y (2010) Glycyrrhetinic acid-modified chitosan/poly (ethylene glycol) nanoparticles for liver-targeted delivery. Biomaterials 31:4748–4756. doi:10.1016/j.biomaterials.2010.02.042

    CAS  PubMed  Google Scholar 

  206. Asl MN, Hosseinzadeh H (2008) Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res 22:709–724

    CAS  PubMed  Google Scholar 

  207. Ishida S, Sakiya Y, Ichikawa T, Taira Z (1993) Uptake of glycyrrhizin by isolated rat hepatocytes. Biol Pharm Bull 16:293–297

    CAS  PubMed  Google Scholar 

  208. Ishida S, Sakiya Y, Taira Z (1994) Disposition of glycyrrhizin in the perfused liver of rats. Biol Pharm Bull 17:960–969

    CAS  PubMed  Google Scholar 

  209. Negishi M, Irie A, Nagata N, Ichikawa A (1991) Specific binding of glycyrrhetinic acid to the rat liver membrane. Biochim Biophys Acta 1066:77–82. doi:10.1016/0005-2736(91)90253-5

    CAS  PubMed  Google Scholar 

  210. Lin A, Liu Y, Huang Y, Sun J, Wu Z, Zhang X, Ping Q (2008) Glycyrrhizin surface-modified chitosan nanoparticles for hepatocyte-targeted delivery. Int J Pharm 359:247–253. doi:10.1016/j.ijpharm.2008.03.039

    CAS  PubMed  Google Scholar 

  211. Agarwal A, Saraf S, Asthana A, Gupta U, Gajbhiye V, Jain NK (2008) Ligand based dendritic systems for tumor targeting. Int J Pharm 350:3–13. doi:10.1016/j.ijpharm.2007.09.024

    CAS  PubMed  Google Scholar 

  212. Zhang L, Gong F, Zhang F, Ma J, Zhang P, Shen J (2013) Targeted therapy for human hepatic carcinoma cells using folate-functionalized polymeric micelles loaded with superparamagnetic iron oxide and sorafenib in vitro. Int J Nanomedicine 8:1517–1524. doi:10.2147/IJN.S43263

    PubMed Central  PubMed  Google Scholar 

  213. Kim TH, Park IK, Nah JW, Choi YJ, Cho CS (2004) Galactosylated chitosan/DNA nanoparticles prepared using water-soluble chitosan as a gene carrier. Biomaterials 25:3783–3792. doi:10.1016/j.biomaterials.2003.10.063

    CAS  PubMed  Google Scholar 

  214. Mansouri S, Cuie Y, Winnik F, Shi Q, Lavigne P, Benderdour M, Beaumont E, Fernandes JC (2006) Characterization of folate-chitosan-DNA nanoparticles for gene therapy. Biomaterials 27:2060–2065. doi:10.1016/j.biomaterials.2005.09.020

    CAS  PubMed  Google Scholar 

  215. Liu Y, Chen Z, Liu C, Yu D, Lu Z, Zhang N (2011) Gadolinium-loaded polymeric nanoparticles modified with Anti-VEGF as multifunctional MRI contrast agents for the diagnosis of liver cancer. Biomaterials 32:5167–5176. doi:10.1016/j.biomaterials.2011.03.077

    CAS  PubMed  Google Scholar 

  216. Hong G, Yuan R, Liang B, Shen J, Yang X, Shuai X (2008) Folate-functionalized polymeric micelle as hepatic carcinoma-targeted, MRI-ultrasensitive delivery system of antitumor drugs. Biomed Microdevices 10:693–700. doi:10.1007/s10544-008-9180-9

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali, Punjab, 160062, India

    Ashish Kumar Agrawal, Dileep Urimi & Sanyog Jain

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  1. Ashish Kumar Agrawal
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  2. Dileep Urimi
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  3. Sanyog Jain
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  1. Institute of Chemical Technology, Department of Pharmaceutical Sciences and Technology, Mumbai, India

    Padma V. Devarajan

  2. National Institute of Pharmaceutical Education and Research (NIPER), Centre for Pharmaceutical Nanotechnology, Department of Pharmaceutics, Mohali, Punjab, India

    Sanyog Jain

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Agrawal, A.K., Urimi, D., Jain, S. (2015). Multifunctional Polymeric Nano-Carriers in Targeted Drug Delivery. In: Devarajan, P., Jain, S. (eds) Targeted Drug Delivery : Concepts and Design. Advances in Delivery Science and Technology. Springer, Cham. https://doi.org/10.1007/978-3-319-11355-5_15

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