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Clinical Developments in Nanotechnology for Cancer Therapy

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ABSTRACT

Nanoparticle approaches to drug delivery for cancer offer exciting and potentially “game-changing” ways to improve patient care and quality of life in numerous ways, such as reducing off-target toxicities by more selectively directing drug molecules to intracellular targets of cancer cells. Here, we focus on technologies being investigated clinically and discuss numerous types of therapeutic molecules that have been incorporated within nanostructured entities such as nanoparticles. The impacts of nanostructured therapeutics on efficacy and safety, including parameters like pharmacokinetics and biodistribution, are described for several drug molecules. Additionally, we discuss recent advances in the understanding of ligand-based targeting of nanoparticles, such as on receptor avidity and selectivity.

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REFERENCES

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.

    Article  PubMed  Google Scholar 

  2. Heath JR, Davis ME. Nanotechnology and cancer. Annu Rev Med. 2008;59:251–65.

    Article  CAS  PubMed  Google Scholar 

  3. Davis ME, Chen ZG, Shin DM. Nanoparticle therapeutics: an emerging treatment modality for cancer. Nat Rev Drug Discov. 2008;7:771–82.

    Article  CAS  PubMed  Google Scholar 

  4. Venturoli D, Rippe B. Ficoll and dextran vs. globular proteins as probes for testing glomerular permselectivity: effects of molecular size, shape, charge, and deformability. Am J Physiol Ren Physiol. 2005;288:F605–13.

    Article  CAS  Google Scholar 

  5. Choi HS, Liu W, Misra P, Tanaka E, Zimmer JP, Ipe BI, et al. Renal clearance of quantum dots. Nat Biotechnol. 2007;25:1165–70.

    Article  CAS  PubMed  Google Scholar 

  6. 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.

    CAS  PubMed  Google Scholar 

  7. Maeda H, Wu J, Sawa T, Matsumura Y, Hori K. Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Control Release. 2000;65:271–84.

    Article  CAS  PubMed  Google Scholar 

  8. Hobbs SK, Monsky WL, Yuan F, Roberts WG, Griffith L, Torchilin VP, et al. Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment. Proc Natl Acad Sci USA. 1998;95:4607–12.

    Article  CAS  PubMed  Google Scholar 

  9. Dreher MR, Liu W, Michelich CR, Dewhirst MW, Yuan F, Chilkoti A. Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. J Natl Cancer Inst. 2006;98:335–44.

    Article  CAS  PubMed  Google Scholar 

  10. Nomura T, Koreeda N, Yamashita F, Takakura Y, Hashida M. Effect of particle size and charge on the disposition of lipid carriers after intratumoral injection into tissue-isolated tumors. Pharm Res. 1998;15:128–32.

    Article  CAS  PubMed  Google Scholar 

  11. Perrault SD, Walkey C, Jennings T, Fischer HC, Chan WC. Mediating tumor targeting efficiency of nanoparticles through design. Nano Lett. 2009;9:1909–15.

    Article  CAS  PubMed  Google Scholar 

  12. Schluep T, Hwang J, Hildebrandt IJ, Czernin J, Choi CH, Alabi CA, et al. Pharmacokinetics and tumor dynamics of the nanoparticle IT-101 from PET imaging and tumor histological measurements. Proc Natl Acad Sci USA. 2009;106:11394–9.

    Article  CAS  PubMed  Google Scholar 

  13. Choi CH, Alabi CA, Webster P, Davis ME. Mechanism of active targeting in solid tumors with transferrin-containing gold nanoparticles. Proc Natl Acad Sci USA. 2010;107:1235–40.

    Article  CAS  PubMed  Google Scholar 

  14. Park JW. Liposome-based drug delivery in breast cancer treatment. Breast Cancer Res. 2002;4:95–9.

    Article  CAS  PubMed  Google Scholar 

  15. Bartlett DW, Davis ME. Physicochemical and biological characterization of targeted, nucleic acid-containing nanoparticles. Bioconjug Chem. 2007;18:456–68.

    Article  CAS  PubMed  Google Scholar 

  16. Jeong JH, Mok H, Oh YK, Park TG. siRNA conjugate delivery systems. Bioconjug Chem. 2009;20:5–14.

    Article  CAS  PubMed  Google Scholar 

  17. Li SD, Huang L. Pharmacokinetics and biodistribution of nanoparticles. Mol Pharm. 2008;5:496–504.

    Article  CAS  PubMed  Google Scholar 

  18. Alexis F, Pridgen E, Molnar LK, Farokhzad OC. Factors affecting the clearance and biodistribution of polymeric nanoparticles. Mol Pharm. 2008;5:505–15.

    Article  CAS  PubMed  Google Scholar 

  19. Schluep T, Cheng J, Khin KT, Davis ME. Pharmacokinetics and biodistribution of the camptothecin-polymer conjugate IT-101 in rats and tumor-bearing mice. Cancer Chemother Pharmacol. 2006;57:654–62.

    Article  CAS  PubMed  Google Scholar 

  20. Gao S, Dagnaes-Hansen F, Nielsen EJ, Wengel J, Besenbacher F, Howard KA, et al. The effect of chemical modification and nanoparticle formulation on stability and biodistribution of siRNA in mice. Mol Ther. 2009;17:1225–33.

    Article  CAS  PubMed  Google Scholar 

  21. Schluep T, Gunawan P, Ma L, Jensen GS, Duringer J, Hinton S, et al. Polymeric tubulysin-peptide nanoparticles with potent antitumor activity. Clin Cancer Res. 2009;15:181–9.

    Article  CAS  PubMed  Google Scholar 

  22. Gabizon AA, Tzemach D, Horowitz AT, Shmeeda H, Yeh J, Zalipsky S. Reduced toxicity and superior therapeutic activity of a mitomycin C lipid-based produg incorporated in pegylated liposomes. Clin Cancer Res. 2006;12:1913–20.

    Article  CAS  PubMed  Google Scholar 

  23. Numbenjapon T, Wang J, Colcher D, Schluep T, Davis ME, Duringer J, et al. Preclinical results of champtothecin-polymer conjugate (IT-101) in multiple human lymphoma xenograft models. Clin Cancer Res. 2009;15:4365–73.

    Article  CAS  PubMed  Google Scholar 

  24. Chen MY, Hoffer A, Morrison PF, Hamilton JF, Hughes J, Schlageter KS, et al. Surface properties, more than size, limiting convective distribution of virus-sized particles and viruses in the central nervous system. J Neurosurg. 2005;103:311–9.

    Article  PubMed  Google Scholar 

  25. Zahr AS, Davis CA, Pishko MV. Macrophage uptake of core-shell nanoparticles surface modified with poly(ethylene glycol). Langmuir. 2006;22:8178–85.

    Article  CAS  PubMed  Google Scholar 

  26. Kim SH, Jeong JH, Chun KW, Park TG. Target-specific cellular uptake of PLGA nanoparticles coated with poly(L-lysine)-poly(ethylene glycol)-folate conjugate. Langmuir. 2005;21:8852–7.

    Article  CAS  PubMed  Google Scholar 

  27. Dhar S, Gu FX, Langer R, Farokhzad OC, Lippard SJ. Targeted delivery of cisplatin to prostate cancer cells by aptamer functionalized Pt(IV) prodrug-PLGA-PEG nanoparticles. Proc Natl Acad Sci USA. 2008;105:17356–61.

    Article  CAS  PubMed  Google Scholar 

  28. Juliano RL, Alam R, Dixit V, Kang HM. Cell-targeting and cell-penetrating peptides for delivery of therapeutics and imaging agents. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2009;1:324–35.

    Article  CAS  PubMed  Google Scholar 

  29. Hu-Lieskovan S, Heidel JD, Bartlett DW, Davis ME, Triche TJ. Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing’s sarcoma. Cancer Res. 2005;65:8984–92.

    Article  CAS  PubMed  Google Scholar 

  30. Mamot C, Drummond DC, Noble CO, Kallab V, Guo Z, Hong K, et al. Epidermal growth factor receptor-targeted immunoliposomes significantly enhance the efficacy of multiple anticancer drugs in vivo. Cancer Res. 2005;65:11631–8.

    Article  CAS  PubMed  Google Scholar 

  31. Carlson CB, Mowery P, Owen RM, Dykhuizen EC, Kiessling LL. Selective tumor cell targeting using low-affinity, multivalent interactions. ACS Chem Biol. 2007;2:119–27.

    Article  CAS  PubMed  Google Scholar 

  32. Bartlett DW, Su H, Hildebrandt IJ, Weber WA, Davis ME. Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc Natl Acad Sci USA. 2007;104:15549–54.

    Article  CAS  PubMed  Google Scholar 

  33. Kirpotin DB, Drummond DC, Shao Y, Shalaby MR, Hong K, Nielsen UB, et al. Antibody targeting of long-circulating lipidic nanoparticles does not increase tumor localization but does increase internalization in animal models. Cancer Res. 2006;66:6732–40.

    Article  CAS  PubMed  Google Scholar 

  34. Gabizon A, Horowitz AT, Goren D, Tzemach D, Shmeeda H, Zalipsky S. In vivo fate of folate-targeted polyethylene-glycol liposomes in tumor-bearing mice. Clin Cancer Res. 2003;9:6551–9.

    CAS  PubMed  Google Scholar 

  35. Schmidt MM, Wittrup KD. A modeling analysis of the effects of molecular size and binding affinity on tumor targeting. Mol Cancer Ther. 2009;8:2861–71.

    Article  CAS  PubMed  Google Scholar 

  36. Gabizon A, Catane R, Uziely B, Kaufman B, Safra T, Cohen R, et al. Prolonged circulation time and enhanced accumulation in malignant exudates of doxorubicin encapsulated in polyethylene-glycol coated liposomes. Cancer Res. 1994;54:987–92.

    CAS  PubMed  Google Scholar 

  37. Danson S, Ferry D, Alakhov V, Margison J, Kerr D, Jowle D, et al. Phase I dose escalation and pharmacokinetic study of pluronic polymer-bound doxorubicin (SP1049C) in patients with advanced cancer. Br J Cancer. 2004;90:2085–91.

    CAS  PubMed  Google Scholar 

  38. Matsumura Y, Hamaguchi T, Ura T, Muro K, Yamada Y, Shimada Y, et al. Phase I clinical trial and pharmacokinetic evaluations of NK911, a micelle-encapsulated doxorubicin. Br J Cancer. 2004;91:1775–81.

    Article  CAS  PubMed  Google Scholar 

  39. Mross K, Niemann B, Massing U, Drevs J, Unger C, Bhamra R, et al. Pharmacokinetics of liposomal doxorubicin (TLC-D99; Myocet) in patients with solid tumors: an open-label, single-dose study. Cancer Chemother Pharmacol. 2004;54:514–24.

    Article  CAS  PubMed  Google Scholar 

  40. Sutton D, Nasongkla N, Blanco E, Gao J. Functionalized micellar systems for cancer targeted drug delivery. Pharm Res. 2007;24:1029–46.

    Article  CAS  PubMed  Google Scholar 

  41. Batist G. Cardiac safety of liposomal anthracyclines. Cardiovasc Toxicol. 2007;7:72–4.

    Article  CAS  PubMed  Google Scholar 

  42. Maruyama K, Unezaki S, Yuda T, Ishida O, Takahashi N, Suginaka A, et al. Enhanced delivery and antitumor effect of doxorubicin encapsulated in long-circulating liposomes. J Liposome Res. 1994;4:143–65.

    Article  CAS  Google Scholar 

  43. Siegal T, Horowitz A, Gabizon A. Doxorubicin encapsulated in sterically stabilized liposomes for the treatment of a brain tumor model: biodistribution and therapeutic efficacy. J Neurosurg. 1995;83:1029–37.

    Article  CAS  PubMed  Google Scholar 

  44. Rahman AM, Yusuf S, Ewer MS. Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation. Int J Nanomedicine. 2007;2:567–83.

    CAS  PubMed  Google Scholar 

  45. Chia S, Clemons M, Martin LA, Rodgers A, Gelmon K, Pond GR, et al. Pegylated liposomal doxorubicin and trastuzumab in HER-2 overexpressing metastatic breast cancer: a multicenter phase II trial. J Clin Oncol. 2006;24:2773–8.

    Article  CAS  PubMed  Google Scholar 

  46. Vasey PA, Kaye SB, Morrison R, Twelves C, Wilson P, Duncan R, et al. Phase I clinical and pharmacokinetic study of PK1 [N-(2-hydroxypropyl)methacrylaminde copolymer doxorubicin]: first member of a new class of chemotherapeutic agents—drug-polymer conjugates. Clin Cancer Res. 1999;5:83–94.

    CAS  PubMed  Google Scholar 

  47. Seymour LW, Ferry DR, Kerr DJ, Rea D, Whitlock M, Poyner R, et al. Phase II studies of polymer-doxorubicin (PK1, FCE28068) in the treatment of breast, lung and colorectal cancer. Int J Oncol. 2009;34:1629–36.

    Article  CAS  PubMed  Google Scholar 

  48. Seymour LW, Ferry DR, Anderson D, Hesslewood S, Julyan PJ, Payner R, et al. Hepatic drug targeting: phase I evaluation of polymer bound doxorubicin. J Clin Oncol. 2002;20:1668–76.

    Article  CAS  PubMed  Google Scholar 

  49. Duncan R, Vicent MJ. Do HPMA copolymer conjugates have a future as clinically useful nanomedicines? A critical overview of current status and future opportunities. Adv Drug Deliv Rev. 2010;62:272–82.

    Article  CAS  PubMed  Google Scholar 

  50. Cuvier C, Roblot-Treupel L, Millot JM, Lizard G, Chevillard S, Manfair M, et al. Doxorubicin-loaded nanospheres bypass tumor cell multidrug resistance. Biochem Pharmacol. 1992;44:509–17.

    Article  CAS  PubMed  Google Scholar 

  51. Pepin X, Attali L, Domrault C, Gallet S, Metreau JM, Reault Y, et al. On the use of ion-pair chromatography to elucidate doxorubicin release mechanism from polyalkylcyanoacrylate nanoparticles at the cellular level. J Chromatogr B Biomed Sci Appl. 1997;702:181–91.

    Article  CAS  PubMed  Google Scholar 

  52. Lippens RJ. Liposomal daunorubicin (DaunoXome) in children with recurrent or progressive brain tumors. Pediatr Hematol Oncol. 1999;16:131–9.

    Article  CAS  PubMed  Google Scholar 

  53. Lowis S, Lewis I, Elsworth A, Weston C, Doz F, Vassal G, et al. A Phase I study of intravenous liposomal daunorubicin (DaunoXome) in paediatric patients with relapsed or resistant solid tumors. Br J Cancer. 2006;95:571–80.

    Article  CAS  PubMed  Google Scholar 

  54. Gaucher G, Marchessault RH, Leroux JC. Polyester-based micelles and nanoparticles for the parenteral delivery of taxanes. J Control Release. 2010;143:2–12.

    Google Scholar 

  55. Miele E, Spinelli GP, Miele E, Tomao F, Tomao S. Albumin-bound formulation of paclitaxel (Abraxane® ABI-007) in the treatment of breast cancer. Int J Nanomedicine. 2009;4:99–105.

    CAS  PubMed  Google Scholar 

  56. Ibrahim NK, Desai N, Legha S, Soon-Shiong P, Theriault RL, Rivera E, et al. Phase I and pharmacokinetic study of ABI-007, a Cremophor-free, protein-stabilized, nanoparticle formulation of paclitaxel. Clin Cancer Res. 2002;8:1038–44.

    CAS  PubMed  Google Scholar 

  57. Nabholtz JM, Gelmon K, Bontenbal M, Spielmann M, Catimel G, Conte P, et al. Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer. J Clin Oncol. 1996;14:1858–67.

    CAS  PubMed  Google Scholar 

  58. Gradishar WJ, Tjulandin S, Davidson N, Shaw H, Desai N, Bhar P, et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol. 2005;23:7794–803.

    Article  CAS  PubMed  Google Scholar 

  59. Sparreboom A, Scripture CD, Trieu V, Williams PJ, De T, Yang A, et al. Comparative preclinical and clinical pharmacokinetics of a Cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated with Cremophor (Taxol). Clin Cancer Res. 2005;11:4136–43.

    Article  CAS  PubMed  Google Scholar 

  60. Gardner ER, Dahut WL, Scripture CD, Jones J, Aragon-Ching JB, Desai N, et al. Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Clin Cancer Res. 2008;14:4200–5.

    Article  CAS  PubMed  Google Scholar 

  61. Gueritte-Voegelein F, Guenard D, Lavelle F, Le Goff MT, Mangatal L, Potier P. Relationships between the structure of taxol analogues and their antimitotic activity. J Med Chem. 1991;34:992–8.

    Article  CAS  PubMed  Google Scholar 

  62. Boddy AV, Plummer ER, Todd R, Sludden J, Griffin M, Robson L, et al. A Phase I and pharmacokinetic study of paclitaxel poliglumex (XYOTAX), investigating both 3-weekly and 2-weekly schedules. Clin Cancer Res. 2005;11:7834–40.

    Article  CAS  PubMed  Google Scholar 

  63. Chipman SD, Oldham FB, Pezzoni G, Singer JW. Biological and clinical characterization of paclitaxel poliglumex (PPX, CT-2103), a macromolecular polymer-drug conjugate. Int J Nanomedicine. 2006;1:375–83.

    Article  CAS  PubMed  Google Scholar 

  64. Shaffer SA, Baker-Lee C, Kennedy J, Lai MS, de Vries P, Buhler K, et al. In vitro and in vivo metabolism of paclitaxel poliglumex: identification of metabolites and active proteases. Cancer Chemother Pharmacol. 2007;59:537–48.

    Article  CAS  PubMed  Google Scholar 

  65. Mita M, Mita A, Sarantopoulous J, Takimoto CH, Rowinsky EK, Romero O, et al. Phase I study of paclitaxel poliglumex administered weekly for patients with advanced solid malignancies. Cancer Chemother Pharmacol. 2009;64:287–95.

    Article  CAS  PubMed  Google Scholar 

  66. Li C, Wallace S. Polymer-drug conjugates: recent development in clinical oncology. Adv Drug Deliv Rev. 2008;60:886–98.

    Article  CAS  PubMed  Google Scholar 

  67. O’Brien ME, Socinski MA, Popovich AY, Bondarenko IN, Tomova A, Bilynsky BT, et al. Randomized phase III trial comparing single-agent paclitaxel Poliglumex (CT-2103, PPX) with single-agent gemcitabine or vinorelbine for the treatment of PS 2 patients with chemotherapy-naïve advanced non-small cell lung cancer. J Thorac Oncol. 2008;3:728–34.

    Article  PubMed  Google Scholar 

  68. Albain KS, Belani CP, Bonomi P, O’Byrne KJ, Schiller JH, Socinski M. PIONEER: a phase III randomized trial of paclitaxel poliglumex versus paclitaxel in chemotherapy-naïve women with advanced-stage non-small-cell lung cancer and performance status of 2. Clin Lung Cancer. 2006;7:417–9.

    Article  CAS  PubMed  Google Scholar 

  69. Kim SC, Kim DW, Shim YH, Bang JS, Oh HS, Kim SW, et al. In vivo evaluation of polymeric micellar paclitaxel formulation: toxicity and efficacy. J Control Release. 2001;72:191–202.

    Article  CAS  PubMed  Google Scholar 

  70. Kim TY, Kim DW, Chung JY, Shin SG, Kim SC, Heo DS, et al. Phase I and pharmacokinetic study of Genexol-PM, a Cremophor-free, polymeric micelle-formulated paclitaxel, in patients with advanced malignancies. Clin Cancer Res. 2004;10:3708–16.

    Article  CAS  PubMed  Google Scholar 

  71. Lim WT, Tan EH, Toh CK, Hee SW, Leong SS, Ang PC, et al. Phase I pharmacokinetic study of a weekly liposomal paclitaxel formulation (Genexol®-PM) in patients with solid tumors. Ann Oncol. 2010;21:382–8.

    Article  CAS  PubMed  Google Scholar 

  72. Lee KS, Chung HC, Im SA, Park YH, Kim CS, Kim SB, et al. Multicenter phase II trial of Genexol-PM, a Cremophor-free, polymeric micelle formulation of paclitaxel, in patients with metastatic breast cancer. Breast Cancer Res Treat. 2008;108:241–50.

    Article  CAS  PubMed  Google Scholar 

  73. Kim DW, Kim SY, Kim HK, Kim SW, Shin SW, Kim JS, et al. Multicenter phase II trial of Genexol-PM, a novel Cremophor-free, polymeric micelle formulation of paclitaxel, with cisplatin in patients with advanced non-small-cell lung cancer. Ann Oncol. 2007;18:2009–14.

    Article  PubMed  Google Scholar 

  74. Zhang JA, Xuan T, Parmar M, Ma L, Ugwu S, Ali S, et al. Development and characterization of a novel liposomes-based formulation of SN-38. Int J Pharm. 2004;270:93–107.

    Article  CAS  PubMed  Google Scholar 

  75. Homsi J, Simon GR, Garrett CR, Springett G, De Conti R, Chiappori AA, et al. Phase I trial of poly-L-glutamate camptothecin (CT-2106) administered weekly in patients with advanced solid malignancies. Clin Cancer Res. 2007;13:5855–61.

    Article  CAS  PubMed  Google Scholar 

  76. Yurkovetskiy AV, Hiller A, Syed S, Yin M, Lu XM, Fischman AJ, et al. Synthesis of a macromolecular camptothecin conjugate with dual phase drug release. Mol Pharm. 2004;1:375–82.

    Article  CAS  PubMed  Google Scholar 

  77. Schoemaker NE, van Kesteren C, Rosing H, Jansen S, Swart M, Lieverst J, et al. A phase I clinical and pharmacokinetic study of MAG-CPT, a water-soluble polymer conjugate of camptothecin. Br J Cancer. 2002;87:608–14.

    Article  CAS  PubMed  Google Scholar 

  78. Bissett D, Cassidy J, de Bono JS, Muirhead F, Main M, Robson L, et al. Phase I and pharmacokinetic (PK) study of MAG-CPT (PNU 166148): a polymeric derivative of camptothecin (CPT). Br J Cancer. 2004;91:50–5.

    Article  CAS  PubMed  Google Scholar 

  79. Davis ME. Design and development of IT-101, a cyclodextrin-containing polymer conjugate of camptothecin. Adv Drug Deliv Rev. 2009;61:1189–92.

    Article  CAS  PubMed  Google Scholar 

  80. Schluep T, Hwang J, Cheng J, Heidel JD, Bartlett DW, Hollister B, et al. Preclinical efficacy of the camptothecin-polymer conjugate IT-101 in multiple cancer models. Clin Cancer Res. 2006;12:1606–14.

    Article  CAS  PubMed  Google Scholar 

  81. Sankhala KK, Mita AC, Adinin R, Wood L, Beeram M, Bullock S, et al. A Phase I pharmacokinetic (PK) study of MBP-426, a novel liposome encapsulated oxaliplatin. J Clin Oncol. 2009;27:2535.

    Google Scholar 

  82. Boulikas T. Clinical overview on Lipoplatin: a successful liposomal formulation of cisplatin. Expert Opin Investig Drugs. 2009;18:1197–218.

    Article  CAS  PubMed  Google Scholar 

  83. Boulikas T. Molecular mechanisms of cisplatin and its liposomally encapsulated form, Lipoplatin™. Lipoplatin™ as a chemotherapy and antiangiogenesis drug. Cancer Ther. 2007;5:349–76.

    Google Scholar 

  84. Nowotnik DP, Cvitkovic E. ProLindac (AP5346): a review of the development of an HPMA DACH platinum polymer therapeutic. Adv Drug Deliv Rev. 2009;61:1214–9.

    Article  CAS  PubMed  Google Scholar 

  85. Rademaker-Lakhai JM, Terret C, Howell SB, Baud CM, De Boer RF, Pluim D, et al. A Phase I and pharmacological study of the platinum polymer AP5280 given as an intravenous infusion once every 3 weeks in patients with solid tumors. Clin Cancer Res. 2004;10:3386–95.

    Article  CAS  PubMed  Google Scholar 

  86. Zhou Q, Sun X, Zeng L, Liu J, Zhang Z. A randomized multicenter phase II clinical trial of mitoxantrone-loaded nanoparticles in the treatment of 108 patients with unresected hepatocellular carcinoma. Nanomedicine. 2009;5:419–23.

    CAS  PubMed  Google Scholar 

  87. Posey 3rd JA, Saif MW, Carlisle R, Goetz A, Rizzo J, Stevenson S, et al. Phase 1 study of weekly polyethylene glycol-camptothecin in patients with advances solid tumors and lymphomas. Clin Cancer Res. 2005;11:7866–71.

    Article  CAS  PubMed  Google Scholar 

  88. Scott LC, Yao JC, Benson 3rd AB, Thomas AL, Falk S, Mena RR, et al. A phase II study of pegylated-camptothecin (pegamotecan) in the treatment of locally advanced and metastatic gastric and gastro-oesophageal junction adenocarcinoma. Cancer Chemother Pharmacol. 2009;63:363–70.

    Article  CAS  PubMed  Google Scholar 

  89. Sapra P, Zhao H, Mehlig M, Malaby J, Kraft P, Longley C, et al. Novel delivery of SN38 markedly inhibits tumor growth in xenografts, including a camptothecin-11-refractory model. Clin Cancer Res. 2008;14:1888–96.

    Article  CAS  PubMed  Google Scholar 

  90. Carter PJ, Senter PD. Antibody-drug conjugates for cancer therapy. Cancer J. 2008;14:154–69.

    Article  CAS  PubMed  Google Scholar 

  91. Ducry L, Stump B. Antibody-drug conjugates: linking cytotoxic payloads to monoclonal antibodies. Bioconjug Chem. 2010;21:5–13.

    Article  CAS  PubMed  Google Scholar 

  92. Pisal DS, Kosloski MP, Balu-Iyer SV. Delivery of therapeutic proteins. J Pharm Sci. 2010;99:2557–75.

    Google Scholar 

  93. Bailon P, Berthold W. Polyethylene glycol-conjugated pharmaceutical proteins. Pharm Sci Technol Today. 1998;1:352–6.

    Article  CAS  Google Scholar 

  94. Zeidan A, Wang ES, Wetzler M. Pegasparaginase: where do we stand? Expert Opin Biol Ther. 2009;9:111–9.

    Article  CAS  PubMed  Google Scholar 

  95. Ho DH, Brown NS, Yen A, Holmes R, Keating M, Abuchowski A, et al. Clinical pharmacology of polyethylene glycol-L-asparaginase. Drug Metab Dispos. 1986;14:349–52.

    CAS  PubMed  Google Scholar 

  96. Abshire TC, Pollock BH, Billett AL, Bradley P, Buchanan GR. Weekly polyethylene glycol conjugated L-asparaginase compared with biweekly dosing produces superior induction remission rates in childhood relapsed acute lymphoblastic leukemia: a pediatric oncology group study. Blood. 2000;96:1709–15.

    CAS  PubMed  Google Scholar 

  97. Panetta JC, Gajjar A, Hijiya N, Hak LJ, Cheng C, Liu W, et al. Comparison of native E. coil and PEG asparaginase pharmacokinetics and pharmacodynamics in pediatric acute lymphoblastic leukemia. Clin Pharmacol Ther. 2009;86:651–8.

    Article  CAS  PubMed  Google Scholar 

  98. Chouieri TK, Hutson TE, Bukowski RM. Evolving role of pegylated interferons in metastatic renal cell carcinoma. Expert Rev Anticancer Ther. 2003;3:823–9.

    Article  Google Scholar 

  99. Morishita M, Leonard RC. PEGfilgrastim; a neutrophil mediated granulocyte colony stimulating factor-expanding uses in cancer chemotherapy. Expert Opin Biol Ther. 2008;8:993–1001.

    Article  CAS  PubMed  Google Scholar 

  100. Renwick W, Pettengell R, Green M. Use of filgrastim and pegfilgrastim to support delivery of chemotherapy: twenty years of clinical experience. BioDrugs. 2009;23:175–86.

    Article  CAS  PubMed  Google Scholar 

  101. Gregoriadis G, Jain S, Papaioannou I, Laing P. Improving the therapeutic efficacy of peptides and proteins: a role of polysialic acids. Int J Pharm. 2005;300:125–30.

    Article  CAS  PubMed  Google Scholar 

  102. Mundargi RC, Babu VR, Rangaswamy V, Patel P, Aminabhavi TM. Nano/micro technologies for delivering macromolecular therapeutics using poly(D, L-lactide-co-glycolide) and its derivatives. J Control Release. 2008;125:193–209.

    Article  CAS  PubMed  Google Scholar 

  103. Chan YP, Meyrueix R, Kravtzoff R, Nicolas F, Lundstrom K. Review on Medusa:a polymer-based sustained release technology for protein and peptide drugs. Expert Opin Drug Deliv. 2007;4:441–51.

    Article  CAS  PubMed  Google Scholar 

  104. Apte RS. Pegaptanib sodium for the treatment of age-related macular degeneration. Expert Opin Pharmacother. 2008;9:499–508.

    Article  CAS  PubMed  Google Scholar 

  105. Davis ME. The first targeted delivery of siRNA in humans via a self-assembling, cyclodextrin polymer-based nanoparticle: from concept to clinic. Mol Pharm. 2009;6:659–68.

    Article  CAS  PubMed  Google Scholar 

  106. Heidel JD, Yu Z, Liu JY, Rele SM, Liang Y, Zeidan RK, et al. Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA. Proc Natl Acad Sci USA. 2007;104:5715–21.

    Article  CAS  PubMed  Google Scholar 

  107. Davis ME, Zuckerman JE, Choi CH, Seligson D, Tolcher A, Alabi CA, et al. Evidence of RNAi in humans from systemically delivered siRNA via targeted nanoparticles. Nature. 2010;464:1067–70.

    Google Scholar 

  108. Nemunaitis JM, Nemunaitis J. Potential of Advexin®: a p53 gene-replacement therapy in Li-Fraumeni syndrome. Future Oncol. 2008;4:759–68.

    Article  CAS  PubMed  Google Scholar 

  109. Judge A, McClintock K, Phelps JR, Maclachlan I. Hypersensitivity and loss of disease site targeting caused by antibody responses to PEGylated liposomes. Mol Ther. 2006;13:328–37.

    Article  CAS  PubMed  Google Scholar 

  110. Dams ET, Laverman P, Oyen WJ, Storm G, Scherphof GL, van der Meer JW, et al. Accelerated blood clearance and altered biodistribution of repeated injections of sterically stabilized liposomes. J Pharmacol Exp Ther. 2000;292:1071–9.

    CAS  PubMed  Google Scholar 

  111. Ishida T, Ichihara M, Wang X, Yamamoto K, Kimura J, Majima E, et al. Injection of PEGylated liposomes in rats elicits PEG-specific IgM, which is responsible for rapid elimination of a second dose of PEGylated liposomes. J Control Release. 2006;112:15–25.

    Article  CAS  PubMed  Google Scholar 

  112. Ishida T, Atobe K, Wang X, Kiwada H. Accelerated blood clearance of PEGylated liposomes upon repeated injections: effect of doxorubicin-encapsulation and high-dose first injection. J Control Release. 2006;115:251–8.

    Article  CAS  PubMed  Google Scholar 

  113. Tagami T, Nakamura K, Shimizu T, Ishida T, Kiwada H. Effect of siRNA in PEG-coated siRNA-lipoplex on anti-PEG IgM production. J Control Release. 2009;137:234–40.

    Article  CAS  PubMed  Google Scholar 

  114. Tagami T, Nakamura K, Shimizu T, Yamazaki N, Ishida T, Kiwada H. CpG motifs in pDNA-sequences increase anti-PEG IgM production induced by PEG-coated pDNA-lipoplexes. J Control Release. 2010;142:160–6.

    Article  CAS  PubMed  Google Scholar 

  115. Ishihara T, Takeda M, Sakamoto H, Kimoto A, Kobayashi C, Takasaki N, et al. Accelerated blood clearance phenomenon upon repeated injection of PEG-modified PLA-nanoparticles. Pharm Res. 2009;26:2270–9.

    Article  CAS  PubMed  Google Scholar 

  116. Martinez AL, Sherman MR, Saifer MG, Williams LD. US Pat Appl. 20040062746. Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof. 2004.

  117. Martinez AL, Sherman MR, Saifer MG, Williams LD. US Pat Appl. 20040062748. Polymer conjugates with decreased antigenicity, methods of preparation and uses thereof. 2004.

  118. Daniels TR, Delgado T, Rodriguez JA, Helguera G, Penichet ML. The transferrin receptor part I: biology and targeting with cytotoxicity antibodies for the treatment of cancer. Clin Immunol. 2006;121:144–58.

    Article  CAS  PubMed  Google Scholar 

  119. Daniels TR, Delgado T, Helguera G, Penichet ML. The transferrin receptor part II: targeted delivery of therapeutic agents into cancer cells. Clin Immunol. 2006;121:159–76.

    Article  CAS  PubMed  Google Scholar 

  120. Zhou Y, Drummond DC, Zou H, Hayes ME, Adams GP, Kirpotin DB, et al. Impact of single-chain Fv antibody fragment affinity on nanoparticle targeting of epidermal growth factor receptor-expressing tumor cells. J Mol Biol. 2007;371:934–7.

    Article  CAS  PubMed  Google Scholar 

  121. Baguley BC. Multidrug resistance in cancer. Meth Mol Biol. 2010;596:1–14.

    Article  CAS  Google Scholar 

  122. Minko T, Kopeckova P, Kopecek J. Efficacy of the chemotherapeutic action of HPMA copolymer-bound doxorubicin in a solid tumor model of ovarian carcinoma. Int J Cancer. 2000;86:108–17.

    Article  CAS  PubMed  Google Scholar 

  123. Suzuki R, Takizawa T, Kuwata Y, Mutoh M, Ishiguro N, Utoguchi N, et al. Effective anti-tumor activity of oxaliplatin encapsulated in transferrin-PEG-lispome. Int J Pharm. 2008;346:143–50.

    Article  CAS  PubMed  Google Scholar 

  124. Lee ES, Na K, Bae YH. Doxorubicin loaded pH-sensitive polymeric micelles for reversal of resistant MCF-7 tumor. J Control Release. 2005;103:405–18.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Mark E. Davis.

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Heidel, J.D., Davis, M.E. Clinical Developments in Nanotechnology for Cancer Therapy. Pharm Res 28, 187–199 (2011). https://doi.org/10.1007/s11095-010-0178-7

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