Moving Forward: Expected Opportunities for the Development of New Therapeutic Agents Based on Nanotechnologies

  • F. F. (Russ) Knapp
  • Ashutosh Dash


This chapter provides a detailed overview of the explosive, exponential growth in the use of nanomaterials as carriers for therapeutic radioisotopes using a variety of new unique concepts for radioisotope attachment and targeted delivery. These very small targeting agents for the applications discussed in this chapter are essentially platforms to which therapeutic radioisotopes can be stably attached for transport to the target sites, which are generally tumor cells. Because of their very small size—i.e., at least 100 nm in one dimension—they must be small enough for transit through the small capillaries. As discussed in this chapter, these nanocarriers can be composed of a large variety of materials to which specific targeting moieties and radioisotopes can be attached by many different strategies.


Radionuclide Therapy Mesoporous Silica Nanoparticles Target Radionuclide Therapy Therapeutic Radionuclide Conjugation Strategy 


  1. Albanell J, Baselga J. Trastuzumab. A humanized anti-HER2 monoclonal antibody, for the treatment of breast cancer. Drugs Today. 1999;35:931–46.PubMedGoogle Scholar
  2. Alexis F, Basto P, Levy-Nissenbaum E, et al. HER-2-targeted nanoparticle–affibody bioconjugates for cancer therapy. Chem Med Chem. 2008;3:1839–43.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Allen TM. Ligand-targeted therapeutics in anticancer therapy. Nat Rev Cancer. 2002;2:750–63.PubMedCrossRefGoogle Scholar
  4. Allen TM, Cullis PR. Drug delivery systems: entering the mainstream. Science. 2004;303:1818–22.PubMedCrossRefGoogle Scholar
  5. Allen TM, Hansen C. Pharmacokinetics of stealth versus conventional liposomes: effect of dose. Biochim Biophys Acta. 1991;1068:133–41.PubMedCrossRefGoogle Scholar
  6. Alloatti D, Giannini G, Vesci L, et al. Camptothecins in tumor homing via an RGD sequence mimetic. Bioorg Med Chem Lett. 2012;22(20):6509–12.PubMedCrossRefGoogle Scholar
  7. André S, Frisch B, Kaltner H, Desouza D, et al. Lectin-mediated drug targeting: selection of valency, sugar type (Gal/Lac), and spacer length for cluster glycosides as parameters to distinguish ligand binding to C-type asialoglycoprotein receptors and galectins. Pharm Res. 2000;17:985–90.PubMedCrossRefGoogle Scholar
  8. Astolfo A, Schültke E, Menk RH, et al. In vivo visualization of gold-loaded cells in mice using x-ray computed tomography. Nanomedicine. 2013;9(2):284–92.PubMedCrossRefGoogle Scholar
  9. Bae YH. Drug targeting and tumor heterogeneity. J Control Release. 2009;133:2–3.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Bae YH, Park K. Targeted drug delivery to tumors: myths, reality and possibility. J Controlled Release. 2011;153:198–205.CrossRefGoogle Scholar
  11. Bai S, Thomas C, Rawat A, Ahsan F. Recent progress in dendrimer-based nanocarriers. Crit Rev Ther Drug Carrier Syst. 2006;23:437–95.PubMedCrossRefGoogle Scholar
  12. Bao A, Goins B, Klipper R, et al. Re-186-liposome labeling using Re-186-SNS/S complexes: in vitro stability, imaging, and biodistribution in rats. J Nucl Med. 2003;44:1992–9.PubMedGoogle Scholar
  13. Barua S, Yoo JW, Kolhar P, Wakankar A, Gokarn YR, Mitragotri S, et al. Particle shape enhances specificity of antibody-displaying nanoparticles. Proc Natl Acad Sci. 2013;110(9):3270–5.PubMedPubMedCentralCrossRefGoogle Scholar
  14. Bayraktar H, You C-C, Rotello VM, Knapp MJ. Facial control of nanoparticle binding to cytochrome c. J Am Chem Soc. 2007;129:2732–3.PubMedCrossRefGoogle Scholar
  15. Bhang SH, Won N, Lee T, et al. Hyaluronic acid-quantum dot conjugates for in vivo lymphatic vessel imaging. ACS Nano. 2009;3:1389–98.PubMedCrossRefGoogle Scholar
  16. Brahmachari S, Ghosh M, Dutta S, Das PK. Biotinylated amphiphile-single walled carbon nanotube conjugate for target-specific delivery to cancer cells. J Mater Chem. 2014;B2:1160–73.CrossRefGoogle Scholar
  17. Brigger I, Dubernet C, Couvreur P. Nanoparticles in cancer therapy and diagnosis. Adv Drug Deliv Rev. 2012;54:631–51.CrossRefGoogle Scholar
  18. Byrne JD, Betancourt T, Brannon-Peppas L. Active targeting schemes for nanoparticle systems in cancer therapeutics. Adv Drug Deliv Rev. 2008;60:1615–26.PubMedCrossRefGoogle Scholar
  19. Cai W, Shin DW, Chen K, et al. Peptide-labeled near-infrared quantum dots for imaging tumor vasculature in living subjects. Nano Lett. 2006;6:669–76.PubMedCrossRefGoogle Scholar
  20. Capone PM, Papsidero LD, Chu TM. Relationship between antigen density and immunotherapeutic response elicited by monoclonal antibodies against solid tumors. J Natl Cancer Inst. 1984;72:673–7.PubMedGoogle Scholar
  21. Carlson B. Aptamers: the new frontier in drug development? Biotechnol Health Care. 2007;4:32–6.Google Scholar
  22. Chen Y, Chen HR, Shi JL. In vivo biosafety evaluations and diagnostic/therapeutic applications of chemically designed mesoporous silica nanoparticles. Adv Mater. 2013;25:3144–76.PubMedCrossRefGoogle Scholar
  23. Cho CS, Park IK, Cho CS. Galactosylated Poly(ethylene gly-col)-Chitosan – graft- Polyethylenimine as a gene carrier for hepatocyte-targeting. J Control Release. 2008;131:150–7.PubMedCrossRefGoogle Scholar
  24. Colcher D, Pavlinkova G, Beresford G, et al. Pharmacokinetics and biodistribution of genetically engineered antibodies. Q J Nucl Med. 1998;42:225–41.PubMedGoogle Scholar
  25. Daniels TR, Bernabeu E, Rodriguez JA, et al. The transferrin receptor and the targeted delivery of therapeutic agents against cancer. Biochim Biophys Acta. 2012;1820:291–317.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Dill K, Lin M, Poteras C, Fraser C, et al. Antibody-antigen binding constants determined in solution-phase with the threshold membrane-capture system-binding constants for antifluorescein, anti-saxitoxin, and anti-ricin antibodies. Anal Biochem. 1994;217:128–38.PubMedCrossRefGoogle Scholar
  27. Doi KT, Akaike H, Horie Y, et al. Excessive production of nitric oxide in rat solid tumor and its implication in rapid tumor growth. Cancer. 1996;77:1598–604.PubMedCrossRefGoogle Scholar
  28. Dreher MR, Liu W, Michelich CR, et al. Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. J Natl Cancer Inst. 2006;98:335–44.PubMedCrossRefGoogle Scholar
  29. Drolet DW, Nelson J, Tucker CE, et al. Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (NX1838) following injection into the vitreous humor of rhesus monkeys. Pharm Res. 2000;17:1503–10.PubMedCrossRefGoogle Scholar
  30. Duncan R, Vincent MJ, Greco F, et al. Polymer–drug conjugates: towards a novel approach for the treatment of endocrine-related cancer. Endocrinol Relat Cancer. 2005;12:S189–S19.CrossRefGoogle Scholar
  31. Ellington AD, Ebright J, Chu T, Levy M. Using aptamers for cell-specific labeling and delivery. In: American Association for Cancer Research education book. Philadelphia: American Association for Cancer Research; 2007. p. 51–5.Google Scholar
  32. Fahmy TM, Samstein RM, Harness CC, Saltzman WM. Surface modification of biodegradable polyesters with fatty acid conjugates for improved drug targeting. Biomaterials. 2005;26:5727–36.PubMedCrossRefGoogle Scholar
  33. Fang C, Bhattarai N, Sun C, Zhang M. Functionalized nanoparticles with long-term stability in biological media. Small. 2009;5:1637–41.PubMedPubMedCentralCrossRefGoogle Scholar
  34. Faraji A, Wipf P. Nanoparticles in cellular drug delivery. Bioorg Med Chem. 2004;17:2950–62.CrossRefGoogle Scholar
  35. Farokhzad OC, Jon S, Khademhosseini A, et al. Nanoparticle–aptamer bioconjugates. A new approach for targeting prostate cancer cells. Cancer Res. 2004;64:7668–72.PubMedCrossRefGoogle Scholar
  36. Farokhzad OC, Karp JM, Langer R. Nanoparticle–aptamer bioconjugates for cancer targeting. Expert Opin Drug Deliv. 2006;3:311–24.PubMedCrossRefGoogle Scholar
  37. Ferrara N. VEGF as a therapeutic target in cancer. Oncology. 2005;69:11–6.PubMedCrossRefGoogle Scholar
  38. Figuerola A, Di Corato R, Manna L, Pellegrino T. From iron oxide nanoparticles towards advanced iron-based inorganic materials designed for biomedical applications. Pharmacol Res. 2010;62:126–43.PubMedCrossRefGoogle Scholar
  39. Fischer MJ. Amine coupling through EDC/NHS: a practical approach. In: Nico NJ, Fisher MJE, editors. Surface Plasmon Reson. New York: Humana Press: 2010:55–73. ISBN 978-1-60761-670-2.Google Scholar
  40. Foraker AB, Khantwal CM, Swaan PW. Current perspectives on the cellular uptake and trafficking of riboflavin. Adv Drug Deliv Rev. 2003;55:1467–83.PubMedCrossRefGoogle Scholar
  41. Galow TH, Boal AK, Rotello VM. “Building block” approach to mixed-colloid systems through electrostatic self-organization. Adv Mater. 2000;12:576–9.CrossRefGoogle Scholar
  42. Gao XH, Cui YY, Levenson RM, et al. In vivo cancer targeting and imaging with semiconductor quantum dots. Nat Biotechnol. 2004;22:969–76.PubMedCrossRefGoogle Scholar
  43. Gao J, Feng SS, Guo Y. Antibody engineering promotes nanomedicine for cancer treatment. Nanomedicine. 2010;5:1141–5.PubMedCrossRefGoogle Scholar
  44. Gao WL, Ji L, Li G, Cui K, Xu P, Tang B. Bifunctional combined Au-Fe2O3 nanoparticles for induction of cancer cell-specific apoptosis and real-time imaging. Biomaterials. 2012;33:710–3718.Google Scholar
  45. Gregory AE, Titball R, Williamson D. Vaccine delivery using nanoparticles. Front Cell Infect Microbiol. 2013;3:13.PubMedPubMedCentralCrossRefGoogle Scholar
  46. Gunthert U, Hofmann M, Rudy W, et al. A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Cell. 1991;65:13–24.PubMedCrossRefGoogle Scholar
  47. Hanahan D, Weinberg RA. Hall marks of cancer: the next generation. Cell. 2011;144:646–74.PubMedCrossRefGoogle Scholar
  48. Harrington KJ, Mohammadtaghi S, Uster PS, et al. Effective targeting of solid tumors in patients with locally advanced cancers by radiolabeled PEGylated liposomes. Clin Cancer Res. 2001;7:243–54.PubMedGoogle Scholar
  49. He QJ, Shi JL. Mesoporous silica nanoparticle based nano drug delivery systems: synthesis, controlled drug release and delivery, pharmacokinetics and biocompatibility. J Mater Chem. 2011;21:5845–55.CrossRefGoogle Scholar
  50. He C, Hu Y, Yin L, et al. Effects of particle size and surface charge on cellular uptake and biodistribution of polymeric nanoparticles. Biomaterials. 2010a;31:3657–66.PubMedCrossRefGoogle Scholar
  51. He QJ, Shi JL, Zhu M, Chen Y, Chen F. The three-stage in vitro degradation behavior of mesoporous silica in simulated body fluid. Micropor Mesopor Ma. 2010b;131:314–20.CrossRefGoogle Scholar
  52. Hicke BJ, Stephens AW. Escort aptamers: a delivery service for diagnosis and therapy. J Clin Invest. 2000;106:923–8.PubMedPubMedCentralCrossRefGoogle Scholar
  53. Hild W, Pollinger K, Caporale A, Cabrele C, Keller M, Pluym N, Buschauer A, Rachel R, Tessmar J, Breunig M, Goepferich A. G protein-coupled receptors function as logic gates for nanoparticle binding and cell uptake. Proc Natl Acad Sci USA. 2010;107:10667–72.PubMedPubMedCentralCrossRefGoogle Scholar
  54. Hilgenbrink AR, Low PS. Folate receptor-mediated drug targeting: from therapeutics to diagnostics. J Pharm Sci. 2005;94:2135–46.PubMedCrossRefGoogle Scholar
  55. Ho JA, Hung CH. Using liposomal fluorescent biolabels to develop an immunoaffinity chromatographic biosensing system for biotin. Anal Chem. 2008;80:6405–9.PubMedCrossRefGoogle Scholar
  56. Hobbs SK, Monsky WL, Yuan F, et al. Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc Natl Acad Sci U S A. 1998;95:4607–12.PubMedPubMedCentralCrossRefGoogle Scholar
  57. Hoefnagel CA. Radionuclide cancer therapy. Ann Nucl Med. 1998;12:61–70.PubMedCrossRefGoogle Scholar
  58. Hofheinz RD, al-Batran SE, Hartmann F, et al. Stromal antigen targeting by a humanized monoclonal antibody: an early phase II trial of sibrotuzumab in patients with metastatic colorectal cancer. Onkologie. 2003;26:44–4.PubMedCrossRefGoogle Scholar
  59. Holliger P, Hudson P. Engineered antibody fragments and the rise of single domains. Nat Biotechnol. 2005;23(9):1126–36.PubMedCrossRefGoogle Scholar
  60. Holmberg RJ, Bolduc S, Beauchemin D, et al. Characteristics of colored passive layers on zirconium: morphology, optical properties, and corrosion resistance. ACS Appl Mater Interfaces. 2012;4:6487–98.PubMedCrossRefGoogle Scholar
  61. Hong R, Fischer NO, Verma A, et al. Control of protein structure and function through surface recognition by tailored nanoparticle scaffolds. J Am Chem Soc. 2004;126:739–43.PubMedCrossRefGoogle Scholar
  62. Hu FX, Neoh KG, Kang ET. Synthesis and in vitro anti-cancer evaluation of tamoxifen-loaded magnetite/PLLA composite nanoparticles. Biomaterials. 2006;27:5725–33.PubMedCrossRefGoogle Scholar
  63. Huang G, Zhou Z, Srinivasan R, et al. Affinity manipulation of surface-conjugated RGD peptide to modulate binding of liposomes to activated platelets. Biomaterials. 2008;29(11):1676–85.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Huang YF, Lin YW, Lin Z-H, Chang HT. Aptamer-modified gold nanoparticles for targeting breast cancer cells through light scattering. J Nanopart Res. 2009;11:775–83.CrossRefGoogle Scholar
  65. Huang FY, Lee J, Kao TW, et al. Imaging, autoradiography, and biodistribution of Re- 188-labeled PEGylated nanoliposome in orthotopicglioma bearing rat model. Cancer Biother Radiopharm. 2011;26:717–25.PubMedPubMedCentralCrossRefGoogle Scholar
  66. Iyer AK, Khaled G, Fang J, Maeda H. Exploiting the enhanced permeability and retention effect for tumor targeting. Drug Discov Today. 2006;11:812–8.PubMedCrossRefGoogle Scholar
  67. James JS, Dubs G. FDA approves new kind of lymphoma treatment. AIDS Treat News. 1997;284:2–3.Google Scholar
  68. Jenison RD, Gill SC, Pardi A, Polisky B. High-resolution molecular discrimination by RNA. Science. 1994;263(5152):1425–9.PubMedCrossRefGoogle Scholar
  69. Jiang XZ, Housni A, Gody G, et al. Synthesis of biotinylated alpha-D-mannoside or N-acetyl beta-D-glucosaminoside decorated gold nanoparticles: study of their biomolecular recognition with Con A and WGA lectins. Bioconjug Chem. 2010;21:521–30.PubMedCrossRefGoogle Scholar
  70. Kamaly N, Xiao Z, Valencia PM, et al. Targeted polymeric therapeutic nanoparticles: design, development and clinical translation. Chem Soc Rev. 2012;41:2971–3010.PubMedPubMedCentralCrossRefGoogle Scholar
  71. Kataoka K, Harada A, Nagasaki Y. Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv Drug Deliv Rev. 2001;47:113–31.PubMedCrossRefGoogle Scholar
  72. Khosroshahi AG, Amanlou M, Sabzevari O, et al. A comparative study of two novel nanosized radiolabeled analogues of methionine for SPECT tumor imaging. Curr Med Chem. 2013;20:123–33.PubMedCrossRefGoogle Scholar
  73. Kikkeri R, Lepenies B, Adibekian A, et al. In vitro imaging and in vivo liver targeting with carbohydrate capped quantum dots. J Am Chem Soc. 2009;131:2110–2.PubMedCrossRefGoogle Scholar
  74. Kim EM, Jeong HJ, Moon MH. Asialoglycoprotein receptor targeted gene delivery using galactosylated polyethylenimine-graft -poly (ethylene glycol): in vitro and in vivo studies. J Control Release. 2005;108:557–67.PubMedCrossRefGoogle Scholar
  75. Kocbek PN, Obermajer M, Cegnar J, et al. Targeting cancer cells using PLGA nanoparticles surfacemodifiedwith monoclonal antibody. J Control Release. 2007;120:18–26.PubMedCrossRefGoogle Scholar
  76. Kostarelos K, Emfietzoglou D. Tissue dosimetry of liposome-radionuclide complexes for internal radiotherapy: toward liposome-targeted therapeutic radiopharmaceuticals. Anticancer Res. 2000;20:3339–45.PubMedGoogle Scholar
  77. Kostarelos K, Emfietzoglou D, Stamatelou M. Liposome-mediated delivery of radionuclides to tumor models for cancer radiotherapy: a quantitative analysis. J Liposome Res. 1999;9:407–42.CrossRefGoogle Scholar
  78. Kresse M, Wagner S, Pfefferer D, et al. Targeting of ultra small super paramagnetic iron oxide(USPIO) particles to tumor cells in vivo by using transferring receptor pathways. Magn Reson Med. 1998;40:236–42.PubMedCrossRefGoogle Scholar
  79. Kukowska-Latallo JF, Candido KA, Cao Z, et al. Nanoparticle targeting of anticancer drug improves therapeutic response in animal model of human epithelial cancer. Cancer Res. 2005;65:5317–24.PubMedCrossRefGoogle Scholar
  80. Laverman P, Carstens MG, Boerman OC, et al. Factors affecting the accelerated blood clearance of polyethylene glycol-liposomes upon repeated injection. J Pharmacol Exp Ther. 2001;298:607–12.PubMedGoogle Scholar
  81. Lee JF, Stovall GM, Ellington AD. Aptamer therapeutics advance. Curr Opin Chem Biol. 2006;10(3):282–9.PubMedCrossRefGoogle Scholar
  82. Lee JS, Ankone M, Pieters E, et al. Circulation kinetics and biodistribution of dual-labeled polymersomes with modulated surface charge in tumor-bearing mice: comparison with stealth liposomes. J Control Release. 2011;155:282–8.PubMedCrossRefGoogle Scholar
  83. Lee DE, Koo H, Sun IC, et al. Multifunctional nanoparticles for multimodal imaging and theragnosis. Chem Soc Rev. 2012;41:2656–72.PubMedCrossRefGoogle Scholar
  84. Li YM, Hall WA. Targeted toxins in brain tumor therapy. Toxins. 2010;2:2645–62.PubMedPubMedCentralCrossRefGoogle Scholar
  85. Li LL, Xie M, Wang J, et al. Vitamin-responsive mesoporous nanocarrier with DNA aptamer-mediated cell targeting. Chem Commun. 2013;49:5823–5.CrossRefGoogle Scholar
  86. Liong M, Angelos S, Choi E, et al. Mesostructured multifunctional nanoparticles for imaging and drug delivery. J Mater Chem. 2009;19:6251–7.CrossRefGoogle Scholar
  87. Litzinger DC, Buiting AM, van Rooijen N, Huang L. Effect of liposome size on the circulation time and intraorgan distribution of amphipathic poly(ethylene glycol)-containing liposomes. Biochim Biophys Acta. 1994;1190:99–107.PubMedCrossRefGoogle Scholar
  88. Liu Z, Cai W, He L, et al. In vivo biodistribution and highly efficient tumour targeting of carbon nanotubes in mice. Nat Nanotechnol. 2007;2:47–52.PubMedCrossRefGoogle Scholar
  89. Liu T, Li L, Teng X, et al. Single and repeated dose toxicity of mesoporous hollow silica nanoparticles in intravenously exposed mice. Biomaterials. 2011;32:1657–68.PubMedCrossRefGoogle Scholar
  90. Love JC, Estroff LA, Kriebel JK, et al. Self-assembled monolayers of thiolates on metals as a form of nanotechnology. Chem Rev. 2005;105:1103–70.PubMedCrossRefGoogle Scholar
  91. Low PS, Henne WA, Doorneweerd DD. Discovery and development of folic-acid-based receptor targeting for imaging and therapy of cancer and inflammatory diseases. Acc Chem Res. 2008;41:120–9.PubMedCrossRefGoogle Scholar
  92. Lupold SE, Hicke BJ, Lin Y, CoVey DS. Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen. Cancer Res. 2002;62:4029–33.PubMedGoogle Scholar
  93. Maeda H. Polymer conjugated macromolecular drugs for tumor-specific targeting. In: Domb AJ, editor. Polymeric site-specific pharmacotherapy. New York: John Wiley & Sons; 1994. p. 95–116.Google Scholar
  94. Maeda H, Noguchi Y, Sato K, Akaike T. Enhanced vascular permeability in solid tumor is mediated by nitric oxide and inhibited by both new nitric oxide scavenger and nitric oxide synthase inhibitor. Jpn J Cancer Res. 1994;85:331–4.PubMedCrossRefGoogle Scholar
  95. Maeda H, Akaike T, Wu J, Noguchi Y, Sakata Y. Bradykinin and nitric oxide in infectious disease and cancer. Immunopharmacology. 1996;33:222–30.PubMedCrossRefGoogle Scholar
  96. Maeda H, Fang F, Inuzuka T, et al. Vascular permeability enhancement in solid tumor: various factors, mechanisms involved and its implications. Int Immunopharmacol. 2003;3:319–28.PubMedCrossRefGoogle Scholar
  97. Manzano M, Vallet-Regí M. New developments in ordered mesoporous materials for drug delivery. J Mater Chem. 2010;20:5593–604.CrossRefGoogle Scholar
  98. Markert S, Lassmann S, Gabriel B, et al. Alpha-folate receptor expression in epithelial ovarian carcinoma and non-neoplastic ovarian tissue. Anticancer Res. 2008;28:3567–72.PubMedGoogle Scholar
  99. Marrache S, Dhar S. Engineering of blended nanoparticle platform for delivery of mitochondria-acting therapeutics. Proc Natl Acad Sci U S A. 2012;109:16288–93.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 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. 1986;46:6387–92.PubMedGoogle Scholar
  101. McBain SC, Griesenbach U, Xenariou S, et al. Magnetic nanoparticles as gene delivery agents: enhanced transfection in the presence of oscillating magnet arrays. Nanotechnology. 2008;19(40):405102.PubMedCrossRefGoogle Scholar
  102. McLaughlin MF, Robertson D, Pevsner PH, Wall JS, Mirzadeh S, Kennel SJ. LnPO4 nanoparticles doped with Ac-225 and sequestered daughters for targeted alpha therapy. Cancer Biother Radiopharm. 2014;29(1):34–41.PubMedCrossRefGoogle Scholar
  103. Mier W, Babich J, Haberkorn U. Is nano too big? Eur J Nucl Med Mol Imaging. 2014;41:4–6.PubMedPubMedCentralCrossRefGoogle Scholar
  104. Muller RH, Wallis KH. Surface modification of i.v. injectable biodegradable nanoparticles with poloxamer polymers and poloxamine 908. Int J Pharm. 1993;89:25–31.CrossRefGoogle Scholar
  105. Nakanishi T, et al. Development of the polymer micelle carrier system for doxorubicin. J Control Release. 2001;74:295–302.PubMedCrossRefGoogle Scholar
  106. Oda T, Maeda H. Binding to and internalization by cultured cells of neocarzinostatin and enhancement of its actions by conjugation with lipophilic styrene-maleic acid copolymer. Cancer Res. 1987;47:3206–11.PubMedGoogle Scholar
  107. Oda T, Morinaga T, Maeda H. Stimulation of macrophage by polyanions and its conjugated proteins and effect on cell membrane. Proc Soc Exp Biol Med. 1986;181:9–17.PubMedCrossRefGoogle Scholar
  108. Osborne MP, Richardson VJ, Jeyasingh K, Ryman BE. Radionuclide-labeled liposomes – a new lymph node imaging agent. Int J Nucl Med Biol. 1979;6:75–83.PubMedCrossRefGoogle Scholar
  109. Pan W, Yang H, Zhang T, et al. Dual-targeted nanocarrier based on cell surface receptor and intracellular mRNA: an effective strategy for cancer cell imaging and therapy. Anal Chem. 2013;85:6930–5.PubMedCrossRefGoogle Scholar
  110. Pankhurst QA, Connolly J, Jones SK, Dobson J. Applications of magnetic nanoparticles in biomedicine. J Phys D Appl Phys. 2003;36:R167–81.CrossRefGoogle Scholar
  111. Papa A-L, Basu S, Sengupta P, et al. Mechanistic studies of Gemcitabine-loaded nanoplatforms in resistant pancreatic cancer cells. BMC Cancer. 2012;12:419–30.PubMedPubMedCentralCrossRefGoogle Scholar
  112. Park J, Mattessich T, Jay SM, et al. Enhancement of surface ligand display on PLGA nanoparticles with amphiphilic ligand conjugates. J Control Release. 2011;156:109–15.PubMedPubMedCentralCrossRefGoogle Scholar
  113. Parrott MC, Benhabbour SR, Saab C, et al. Synthesis, radiolabeling, and bio-imaging of high-generation polyester dendrimers. J Am Chem Soc. 2009;131:2906–16.PubMedCrossRefGoogle Scholar
  114. Parvin S, Matsui J, Sato E, Miyashita T. Side-chain effect on Langmuir and Langmuir–Blodgett film properties of poly(n-alkylmethacrylamide)-coated magnetic nanoparticle. J Colloid Interface Sci. 2007;313:128–34.PubMedCrossRefGoogle Scholar
  115. Patil YB, Toti US, Khdair A, Ma L, Panyam J. Single-step surface functionalization of polymeric nanoparticles for targeted drug delivery. Biomaterials. 2009;30:859–66.PubMedPubMedCentralCrossRefGoogle Scholar
  116. Peng XH, Qian X, Mao H, et al. Targeted magnetic iron oxide nanoparticles for tumor imaging and therapy. Int J Nanomedicine. 2008;3(3):311–21.PubMedPubMedCentralGoogle Scholar
  117. Platt VM, Szoka Jr FC. Anticancer therapeutics: targeting macromolecules and nanocarriers to hyaluronan or CD44, a hyaluronan receptor. Mol Pharm. 2008;5:474–86.PubMedPubMedCentralCrossRefGoogle Scholar
  118. Potapova R, Mruk R, Prehl S, Mews A, et al. Semiconductor Nanocrystals with Multifunctional Polymer Ligands. J Am Chem Soc. 2003;125:320–1.PubMedCrossRefGoogle Scholar
  119. Quan Q, Xie J, Gao H, et al. HSA coated iron oxide nanoparticles as drug delivery vehicles for cancer therapy. Mol Pharm. 2011;8:1669–76.PubMedPubMedCentralCrossRefGoogle Scholar
  120. Rana K, Reinhart-King CA, King MR. Inducing Apoptosis in Rolling Cancer Cells: A Combined Therapy with Aspirin and Immobilized TRAIL and E-Selectin. Mol Pharm. 2012;9:2219–27.PubMedPubMedCentralGoogle Scholar
  121. Rojas JV, Woodward JD, Chen N, et al. Synthesis and characterization of lanthanum phosphate nanoparticles as carriers for 223Ra and 225Ra for targeted alpha therapy. Nucl Med Biol. 2015;42(7):614–20.PubMedCrossRefGoogle Scholar
  122. Rosenholm JM, Peuhu E, Bate-Eya LT, et al. Cancer-cell-specific induction of apoptosis using mesoporous silica nanoparticles as drug-delivery vectors. Small. 2010;6:1234–41.PubMedCrossRefGoogle Scholar
  123. Sahoo SK, Labhasetwar V. Nanotech approaches to drug delivery and imaging. Drug Discov Today. 2003;8:1112–20.PubMedCrossRefGoogle Scholar
  124. Satija J, Gupta U, Jain NK. Pharmaceutical and biomedical potential of surface engineered dendrimers. Crit Rev Ther Drug Carrier Syst. 2007;24:257–306.PubMedCrossRefGoogle Scholar
  125. Schiffelers RM, Ansari A, Xu J, et al. Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle. Nucleic Acids Res. 2004;32(19):e149.PubMedPubMedCentralCrossRefGoogle Scholar
  126. Senior JH. Fate and behavior of liposomes in vivo: a review of controlling factors. Crit Rev Ther Drug Carrier Syst. 1987;3:123–93.PubMedGoogle Scholar
  127. Shen Z, Wei W, Tanaka H, et al. A galactosamine-mediated drug delivery carrier for targeted liver cancer therapy. Pharmacol Res. 2011;64:410–9.PubMedCrossRefGoogle Scholar
  128. Shenoi MM, Iltis I, Choi J, et al. Nanoparticle delivered vascular disrupting agents (VDAs): use of TNF-alpha conjugated gold nanoparticles for multimodal cancer therapy. Mol Pharm. 2013;10:1683–94.PubMedPubMedCentralCrossRefGoogle Scholar
  129. Shi M, Lu J, Shoichet MS. Organic nanoscale drug carriers coupled with ligands for targeted drug delivery in cancer. J Mater Chem. 2009;19:5485–98.CrossRefGoogle Scholar
  130. Shi J, Xiao Z, Kamaly N, Farokhzad OC. Self-assembled targeted nanoparticles: evolution of technologies and bench to bedside translation. Acc Chem Res. 2011;44:123–34.CrossRefGoogle Scholar
  131. Shuai X, Ai H, Nasongkla N, Kim S, Gao J. Micellar carriers based on block copolymers of poly(epsilon-caprolactone) and poly(ethylene glycol) for doxorubicin delivery. J Control Release. 2004;98:415–26.PubMedCrossRefGoogle Scholar
  132. Shubayev VI, Pisanic TR, Jin SH. Magnetic nanoparticles for theragnostics. Adv Drug Deliv Rev. 2009;61:467–77.PubMedPubMedCentralCrossRefGoogle Scholar
  133. Singh R, Lillard JW. Nanoparticle-based targeted drug delivery. Exp Mol Pathol. 2009;86:215–23.PubMedPubMedCentralCrossRefGoogle Scholar
  134. Smiljanic N, Moreau V, Yockot D, et al. Supramolecular control of oligosaccharide–protein interactions: switchable and tunable ligands for concanavalin a based on β-cyclodextrin. Angew Chem Int Ed. 2006;45:5465–8.CrossRefGoogle Scholar
  135. Smith RAJ, Porteous CM, Gane AM, Murphy MP. Delivery of bioactive molecules to mitochondria in vivo. Proc Natl Acad Sci U S A. 2003;100:5407–12.PubMedPubMedCentralCrossRefGoogle Scholar
  136. Soundararajan A, Bao A, Phillips WT, et al. [186Re]Liposomal doxorubicin (Doxil): in vitro stability, pharmacokinetics, imaging and biodistribution in a head and neck squamous cell carcinoma xenograft model. Nucl Med Biol. 2009;36:515–24.PubMedPubMedCentralCrossRefGoogle Scholar
  137. Sun C, Lee JSH, Zhang MQ. Magnetic nanoparticles in MR imaging and drug delivery. Adv Drug Deliv Rev. 2008;60:1252–65.PubMedPubMedCentralCrossRefGoogle Scholar
  138. Sutton D, Nasongkla N, Blanco E, Gao J. Functionalized micellar systems for cancer targeted drug delivery. Pharm Res. 2007;24:1029–46.PubMedCrossRefGoogle Scholar
  139. Tanaka S, Akaike T, Wu SJ, et al. Modulation of tumor-selective vascular blood flow and extravasation by the stable prostaglandin I2 analogue beraprost sodium. J Drug Target. 2003;11:45–52.PubMedCrossRefGoogle Scholar
  140. Tang FQ, Li LL, Chen D. Mesoporous silica nanoparticles: synthesis, biocompatibility and drug delivery. Adv Mater. 2012;24:1504–34.PubMedCrossRefGoogle Scholar
  141. Teply BA, Rocha FG, Levy-Nissenbaum E, et al. Nanoparticle-aptamer bioconjugates for targeted antineoplastic drug delivery. Am J Drug Deliv. 2006;4:123–30.CrossRefGoogle Scholar
  142. Torchilin VP. PEG-based micelles as carriers of contrast agents for different imaging modalities. Adv Drug Deliv Rev. 2002;54:235–52.PubMedCrossRefGoogle Scholar
  143. Torchilin VP. Micellar nanocarriers: pharmaceutical perspectives. Pharm Res. 2007;24:1–16.PubMedCrossRefGoogle Scholar
  144. Tsuchiya K, Nitta N, Sonoda A, et al. Evaluation of atherosclerotic lesions using dextran- and mannan-dextran-coated uspio: Mri analysis and pathological findings. Int J Nanomedicine. 2012;7:2271–80.PubMedPubMedCentralCrossRefGoogle Scholar
  145. Ulrich AS. Biophysical aspects of using liposomes as delivery vehicles. Biosci Rep. 2002;22:129–50.PubMedCrossRefGoogle Scholar
  146. Vallet-Regí M, Rámila A, del Real RP, Pérez-Pariente J. A new property of MCM-41: drug delivery system. Chem Mater. 2001;13:308–11.CrossRefGoogle Scholar
  147. Van Cutsem E, Köhne CH, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009;360:1408–17.PubMedCrossRefGoogle Scholar
  148. Wang Z, Cuschieri A. Tumour cell labelling by magnetic nanoparticles with determination of intracellular iron content and spatial distribution of the intracellular iron. Int J Mol Sci. 2013;14:9111–25.PubMedPubMedCentralCrossRefGoogle Scholar
  149. Wang AZ, Bagalkot V, Gu F, et al. Novel targeted aptamer–super paramagnetic iron oxide nanoparticle bioconjugates for combined prostate cancer imaging and therapy. Int J Rad Oncol Biol Phys. 2007;69 Suppl 1:S110–1.CrossRefGoogle Scholar
  150. Wang Y, Chen J, Irudayaraj J. Nuclear targeting dynamics of gold nanoclusters for enhanced therapy of HER2+ breast cancer. ACS Nano. 2011;5:9718–25.PubMedCrossRefGoogle Scholar
  151. Wang C, Ma X, Ye S, et al. Protamine Functionalized Single-Walled Carbon Nanotubes for Stem Cell Labeling and In Vivo Raman/Magnetic Resonance/Photoacoustic Triple-Modal Imaging. Adv Funct Mater. 2012;22:2363–75.CrossRefGoogle Scholar
  152. Weber C, Reiss S, Langer K. Preparation of surface modified protein nanoparticles by introduction of sulfhydryl groups. Int J Pharm. 2000;211:67–78.PubMedCrossRefGoogle Scholar
  153. Weissleder R, Kelly K, Sun EY, et al. Cell-specific targeting of nanoparticles by multivalent attachment of small molecules. Nat Biotechnol. 2005;23:1418–23.PubMedCrossRefGoogle Scholar
  154. White RR, Sullenger BA, Rusconi CP. Developing aptamers into therapeutics. J Clin Invest. 2000;106:929–34.PubMedPubMedCentralCrossRefGoogle Scholar
  155. Wu J, Chu CC. Water insoluble cationic poly(ester amide)s: synthesis, characterization and applications. J Mater Chem. 2013;B1:353–60.CrossRefGoogle Scholar
  156. Wu J, Akaike T, Maeda H. Modulation of enhanced vascular permeability in tumors by a bradykinin antagonist, a cyclooxygenase inhibitor, and a nitric oxide scavenger. Cancer Res. 1998;58:159–65.PubMedGoogle Scholar
  157. Wu J, Akaike T, Hayashida K, Okamoto T, et al. Enhanced vascular permeability in solid tumor involving peroxynitrite and matrix metalloproteinase. Jpn J Cancer Res. 2001;92:439–51.PubMedCrossRefGoogle Scholar
  158. Wu W, Chen B, Cheng J, et al. Biocompatibility of Fe3O4/DNR magnetic nanoparticles in the treatment of hematologic malignancies. Int J Nanomedicine. 2010;5:1079–84.PubMedPubMedCentralGoogle Scholar
  159. Wu H, Liu G, Zhang S, Shi J, Zhang L, et al. Biocompatibility, MR imaging and targeted drug delivery of a rattle-type magnetic mesoporous silica nanosphere system conjugated with PEG and cancer-cell-specific ligands. J Mater Chem. 2011;21:3037–45.CrossRefGoogle Scholar
  160. Xing Y, Zhao J, Conti PS, Chen K. Radiolabeled nanoparticles for multimodality tumor imaging. Theranostics. 2014;4:290–306.PubMedPubMedCentralCrossRefGoogle Scholar
  161. Xu X, Zhang Y, Wang X, et al. Radiosynthesis, biodistribution and micro-SPECT imaging study of dendrimer-avidin conjugate. Bioorg Med Chem. 2011;19:1643–8.PubMedCrossRefGoogle Scholar
  162. Yallapu MM, Othman SF, Curtis ET, et al. Multi-functional magnetic nanoparticles for magnetic resonance imaging and cancer therapy. Biomaterials. 2011;32:1890–905.PubMedPubMedCentralCrossRefGoogle Scholar
  163. Yang Y, Zhang Z, Chen L, et al. Galactosylated poly(2-(2-aminoethoxy)ethoxy)phosphazene/DNA complex nanoparticles: in vitro and in vivo evaluation for gene delivery. Biomacromolecules. 2010;11:927–33.PubMedCrossRefGoogle Scholar
  164. Yang P, Gai S, Lin J. Functionalized mesoporous silica materials for controlled drug delivery. Chem Soc Rev. 2012;41:3679–98.PubMedCrossRefGoogle Scholar
  165. Yao N, Xiao W, Wang X, et al. Discovery of targeting ligands for breast cancer cells using the one-bead one-compound combinatorial method. J Med Chem. 2009;52(1):126–33.PubMedPubMedCentralCrossRefGoogle Scholar
  166. Yaun F, Dellian M, Fukumura D, et al. Vascular permeability in a human tumor xenograft: molecular size dependence and cutoff size. Cancer Res. 1995;55:3752–6.Google Scholar
  167. Ying X, Wen HE, Lu WL, et al. Dual-targeting daunorubicin liposomes improve the therapeutic efficacy of brain glioma in animals. J Control Release. 2010;141:183–92.PubMedCrossRefGoogle Scholar
  168. Yumura K, Ui M, Doi H, et al. Mutations for decreasing the immunogenicity and maintaining the function of core streptavidin. Protein Sci. 2013;22:13–221.CrossRefGoogle Scholar
  169. Zhang L, Radovic-Moreno AF, Alexis F, et al. Co-delivery of hydrophobic and hydrophilic drugs from nanoparticle–aptamer bioconjugates. ChemMedChem. 2007;2:1268–71.PubMedCrossRefGoogle Scholar
  170. Zhang H, Ma Y, Sun XL. Recent developments in carbohydrate-decorated targeted drug/gene delivery. Med Res Rev. 2010a;30:270–89.PubMedCrossRefGoogle Scholar
  171. Zhang Y, Sun Y, Xu X, et al. Synthesis, biodistribution, and microsingle photon emission computed tomography (SPECT) imaging study of technetium-99m labeled PEGylated dendrimer poly(amidoamine) (PAMAM)-folic acid conjugates. J Med Chem. 2010b;53:3262–72.PubMedCrossRefGoogle Scholar
  172. Zhang Y, Sun Y, Xu X, et al. Radiosynthesis and micro-SPECT imaging of 99mTc-dendrimer poly(amido)-amine folic acid conjugate. Bioorg Med Chem Lett. 2010c;20:927–31.PubMedCrossRefGoogle Scholar
  173. Zhang F, Lees E, Amin F, et al. Polymer-coated nanoparticles: a universal tool for biolabelling experiments. Small. 2011;7:3113–27.PubMedCrossRefGoogle Scholar
  174. Zhang Q, Neoh KG, Xu LQ, et al. Functionalized mesoporous silica nanoparticles with muco adhesive and sustained drug release properties for potential bladder cancer therapy. Langmuir. 2014;30:6151–61.Google Scholar
  175. Zhao F, Zhao Y, Liu Y, et al. Cellular uptake, intracellular trafficking, and cytotoxicity of nanomaterials. Small. 2011;7:1322–37.PubMedCrossRefGoogle Scholar
  176. Zweit J. Radionuclides and carrier molecules for therapy. Phys Med Biol. 1996;41:1905–14.PubMedCrossRefGoogle Scholar

Copyright information

© Springer India 2016

Authors and Affiliations

  • F. F. (Russ) Knapp
    • 1
  • Ashutosh Dash
    • 2
  1. 1.Nuclear Security and Isotope DivisionOak Ridge National LaboratoryOAK RIDGEUSA
  2. 2.Isotope Production and Applications DivisionBhabha Atomic Research CentreMumbaiIndia

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