Nanoparticle therapeutics: an emerging treatment modality for cancer

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. 288, F605–F613 (2005).

Matsumura, Y. & Maeda, H. A new concept of macromolecular therapies in cancer chemotherapy: mechanism of tumortropic accumulation of proteins and the antitumor agent SMANCS. Cancer Res. 6, 6387–6392 (1986).

Dreher, M. R. et al. Tumor vascular permeability, accumulation, and penetration of macromolecular drug carriers. J. Natl Cancer Inst. 98, 335–344 (2006).

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. 15, 128–132 (1998).

Hu-Lieskovan, S., Heidel, J. D., Bartlett, D. W., Davis, M. E. & Triche, T. J. 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. 65, 8984–8992 (2005).

Chen, M. Y. et al. Surface properties, more than size, limiting convective distribution of virus-sized particles and viruses in the central nervous system. J. Neurosurg. 103, 311–319 (2005).

Gatter, K. C. et al. Transferrin receptors in human tissues: their distribution and possible clinical relevance. J. Clin. Pathol. 36, 539–545 (1983).

Kirpotin, D. B. et al. Antibody targeting of long-circulating lipidic particles does not increase tumor localization but does increase internalization in animal models. Cancer Res. 66, 6732–6740 (2006).

Bartlett, D. W., Su, H., Hildebrandt, I. J., Weber, W. A. & Davis, M. E. Impact of tumor-specific targeting on the biodistribution and efficacy of siRNA nanoparticles measured by multimodality in vivo imaging. Proc. Natl Acad. Sci. USA 104, 15549–15554 (2007).

Popielarski, S. R., Hu-Lieskovan, S., French, S. W., Triche, T. J. & Davis, M. E. A nanoparticle-based model delivery system to guide the rational design of gene delivery to the liver. 2. In vitro and in vivo uptake results. Bioconjug. Chem. 16, 1071–1080 (2005).

Bartlett, D. W. & Davis, M. E. Physicochemical and biological characterization of targeted, nucleic acid-containing nanoparticles. Bioconjug. Chem. 18, 456–468 (2007).

Song, E. et al. Antibody mediated in vivo delivery of small interfering RNAs via cell-surface receptors. Nature Biotech. 23, 709–717 (2005).

Hong, S. et al. The binding avidity of a nanoparticle-based multivalent targeted drug delivery platform. Chem. Biol. 14, 107–115 (2007).

Montet, X., Funovics, M., Montet-Abou, K., Weissleder, R. & Josephson, L. Multivalent effects of RGD peptides obtained by nanoparticle display. J. Med. Chem. 49, 6087–6093 (2006).

Carlson, C. B., Mowery, P., Owen, R. M., Dykhuizen, E. C. & Kiessling, L. L. Selective tumor cell targeting using low-affinity, multivalent interactions. ACS Chem. Biol. 2, 119–127 (2007).

Pommier, Y. Camptothecins and topoisomerase I: a foot in the door. Targeting the genome beyond topoisomerase I with camptothecins and novel anticancer drugs: importance of DNA replication, repair and cell cycle check points. Curr. Med. Chem. Anticancer Agents 4, 429–434 (2004).

Bartlett, D. W. & Davis, M. E. Insights into the kinetics of siRNA-mediated gene silencing from live-cell and live-animal bioluminescent imaging. Nucl. Acid Res. 34, 322–333 (2006).

Bartlett, D. W. & Davis, M. E. Effect of siRNA nuclease stability on the in vitro and in vivo kinetics of siRNA-mediated gene silencing. Biotech. Bioeng. 97, 909–921 (2007).

Zamboni, W. C. Liposomal, nanoparticle, and conjugated formulation of anticancer agents. Clin. Cancer Res. 11, 8230–8234 (2005).

Rahman, A. M., Yusuf S. W. & Ewer, M. S. Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation. Int. J. Nanomedicine 2, 567–583 (2007).

Batist, G. Cardiac safety of liposomal anthracyclines. Cardiovasc. Toxicol. 7, 72–74 (2007).

Uziely, B. et al. Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary Phase I studies. J. Clin. Oncol. 13, 1777–1785 (1995).

Boddy, A. V. et al. A phase I and pharmacokinetic study of paclitaxel poliglumex (XYOTAX), investigating both 3-weekly and 2-weekly schedules. Clin. Cancer Res. 11, 7834–7840 (2005).

Sutton, D., Nasongkla, N., Blanco, E. & Gao, J. Functionalized micellar systems for cancer targeted drug delivery. Pharm. Res. 24, 1029–1046 (2007).

O'Brien, M. E. Single-agent treatment with pegylated liposomal doxorubicin for metastatic breast cancer. Anticancer Drugs 19, 1–7 (2008).

Green, A. E. & Rose P. G. Pegylated liposomal doxorubicin in ovarian cancer. Int. J. Nanomedicine 1, 229–239 (2006).

Chanan-Khan, A. A. & Lee, K. Pegylated liposomal doxorubicin and immunomodulatory drug combinations in multiple myeloma: rationale and clinical experience. Clin. Lymphoma Myeloma 7 (Suppl. 4), S163–S169 (2007).

Sparreboom, A. et al. Comparative preclinical and clinical pharmacokinetics of a Cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in Cremophor (Taxol). Clin. Cancer Res. 11, 4136–4143 (2005).

Gradishar, W. J. 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. 23, 7794–7803 (2005).

Henderson, I. C. & Bhatia, V. Nab-paclitaxel for breast cancer: a new formulation with an improved safety profile and greater efficacy. Expert Rev. Anticancer Ther. 7, 919–943 (2007).

Harris, J. M. & Chess, R. B. Effect of peglyation on pharmaceuticals. Nature Rev. Drug Discov. 2, 214–221 (2003).

Fuertges, F. & Abuchowski, A. The clinical efficacy of poly(ethylene glycol) modified proteins. J. Control. Release 11, 139–148 (1990).

Graham, M. L. Pegaspargase: a review of clinical studies. Adv. Drug Deliv. Rev. 55. 1293–1302 (2003).

Ho, D. H. et al. Clinical pharmacology of polyethylene glycol–asparaginase. Drug Metab. Disposit. 14, 349–352 (1986).

Kurtzberg, J., Moore, J. O. Scudiery, D. & Franklin, A. A phase II study of polyethylene glycol (PEG) conjugated L-asparaginase in patients with refractory acute leukaemias. Proc. Am. Assoc. Cancer Res. 29, 213 (1988).

Abshire, T. C., Pollock, B. H., Billett, A. L., Bradley, P. & Buchanan, G. R. Weekly polyethylene glycol conjugated-asparaginase compared with biweekly dosing produces superior induction remission rates in childhood relapsed acute lymphoblastic leukemia: a Pediatric Oncology Group Study. Blood 96, 1709–1715 (2000).

Cheng, P. N. et al. Pegylated recombinant human Arginase (rhArg-peg 5000Mw) has in vitro and in vitro anti-proliferative potential and apoptotic activities in human hepatocellular carcinoma (HCC). J. Clin. Oncol. 26 (Suppl. 16), 3179 (2005).

Delman, K. A. et al. Phase I/II trial of pegylated arginine deiminase (ADI-PEG20) in unresectable hepatocellular carcinoma. J. Clin. Oncol. 26 (Suppl. 16), 4139 (2005).

Molineux, G. The design and development of pegfilgrastim (PEG-rmetHuG-CSF, Neulasta). Curr. Pharm. Des. 10, 1235–1244 (2004).

Tanaka, H. Satake-Ishikawa, R., Ishikawa M., Matsuki, S. & Asano, K. Pharmacokinetics of recombined human granulocyte colony-stimulating factor conjugated to polyethylene glycol in rats. Cancer Res. 51, 3710–3714 (1991).

Wang, Y. S. et al. Structural and biological characterisation of pegylated recombinant interferon a2b and its therapeutic implications. Adv. Drug Del. Rev. 54, 547–570 (2002).

Fiaherty, L., Heilbrun, L., Marsack, C. & Vaishampayan U. N. Phase II trial of pegylated interferon (Peg-Intron) and thalidomide (Thal) in pretreated metatastic malignant melanomal. J. Clin. Oncol. 23 (Suppl. 16), 7562 (2005).

Bukowski, R. et al. Pegylated interferon a-2b treatment for patients with solid tumors: a phase I/II study. J. Clin. Oncol. 20, 3841–3849 (2002).

Holmes, F. A. et al. Comparable efficacy and safety profiles of once-per-cycle pegfilgrastim and daily injection filgrastim in chemotherapy-induced neutropenia: a multicenter dose-finding study in women with breast cancer. Ann. Oncol. 13, 903–909 (2002).

Posey, J. A. 3rd et al. Phase I study of weekly polyethylene glycol-camptothecin in patients with advanced solid tumors and lymphoma. Clin. Cancer Res. 11, 7866–7871 (2005).

Rowinsky, E. K. et al. A phase I and pharmacokinetic study of pegylated camptothecin as a 1-hour infusion every 3 weeks in patients with advanced solid malignancies. J. Clin. Oncol. 21, 148–157 (2003).

Scott, L. C. et al. A phase II study of pegylated-camptothecin (pegamotecan) in the treatment of locally advanced and metastatic gastric and gastro-oesophageal junction adnenocarcinoma. Cancer Chemother. Pharmacol. 9 April 2008 (doi:10.1007/s00280-008-0746-2).

Shaffer, S. A. et al. Proteolysis of Xyotax™ by lysosomal cathepsin B; metabolic profiling in tumor cells using LC-MS. Eur. J. Cancer 38 (Suppl. 7), S129 (2002).

Singer, J. W. et al. Poly-(L)-glutamic acid-paclitaxel (CT-2103) [XYOTAX], a biodegradable polymeric drug conjugate: characterization, preclinical pharmacology, and preliminary clinical data. Adv. Exp. Med. Biol. 519, 81–99 (2003).

Singer, J. W. et al. Paclitaxel poliglumex (XYOTAX; CT-2103) [XYOTAX™]: an intracellularly targeted taxane. Anticancer Drugs 16, 243–254 (2005).

Todd, R. et al. Phase I and pharmacological study of CT-2103, a poly(L-glutamic acid)-paclitaxel conjugate. Proc. AACR-NCI-EORTC 12th Int. Conf. Mol. Targets Cancer Therapeut. Discov. Develop. Clin. Valid. Abstract 439 (2001).

Langer, C. J. et al. Paclitaxel poliglumex (PPX)/carboplatin vs. Paclitaxel/carboplatin for the treatment of PS2 patients with chemotherapy-naive advanced non-small cell lung cancer (NSCLC): a phase III study. J. Clin. Oncol. 23 (Suppl. 16), LBA7011 (2005).

Socinski, M. & Ramalingham, S. XYOTAX in NSCLC and other solid tumors. Emerging evidence on biological differences between men and women: is gender-specific therapy warranted? Chemotherapy Foundation web site [online], (2005).

Kremer, M., Judd, J., Rifkin, B., Auszmann, J. & Oursler, M. J. Estrogen modulation of osteoclast lysosomal-enzyme secretion. J. Cell. Biochem. 57, 271–279 (1995).

Homsi, J. et al. Phase I trial of poly-L-glutamate camptothecin (CT-2106) administered weekly in patient with advanced solid malignancies. Clin. Cancer Res. 13, 5855–5861 (2007).

Seymour, L. W. et al. Tumouritropism and anticancer efficacy of polymer-based doxorubicin prodrugs in the treatment of subcutaneous murine B16F10 melanoma. Br. J. Cancer 70, 636–641 (1994).

Duncan, R. et al. Preclinical evaluation of polymer-bound doxorubicin. J. Control. Release 19, 331–346 (1992).

Vasey, P. et al. Phase I clinical and pharmacokinetic study of PKI (HPMA copolymer doxorubicin) first member of a new class of chemotherapeutics agents: drug–polymer conjugates. Clin. Cancer Res. 5, 83–94 (1999).

Thomson, A. H. et al. Population pharmacokinetics in phase I drug development: a phase I study of PK1 in patients with solid tumors. Br. J. Cancer 81, 99–107 (1999).

Duncan, R. Designing polymer conjugates as lysomsomotropic nanomedicines. Biochem. Soc. Trans. 35, 56–60 (2007).

Matsumura, Y. et al. Phase I clinical trial and pharmacokinetic evaluation of NK911, a micelle-encapsulated doxorubicin. Br. J. Cancer. 91, 1775–1781 (2004).

Danson, S. et al. Phase I dose escalation and pharmacokinetic study of pluronic polymer-bound doxorubicin (SP1049C) in patients with advanced cancer. Br. J. Cancer. 11, 2085–2091 (2004).

Armstrong, A. et al. SP1049C as first-line therapy in advanced (inoperable or metatastic) adenocarcinoma of the oesophagus: a phase II window study. J. Clin. Oncol. 24, 4080 (2006).

Kim, T. Y. 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. 10, 3708–3716 (2004).

Lee K. S. et al. Multicenter phase II study of a cremophor-free polymeric micelle-formulated paclitaxel in patients with metastatic breast cancer. J. Clin. Oncol. 24, (Suppl. 18), 10520 (2006).

Yen, Y. et al. First-in-human phase I trial of a cyclodextrin-containing polymer-camptothecin nanoparticle in patients with various solid tumors. J. Clin. Oncol. 25 (Suppl. 18), 14078 (2007).

Schluep, T. et al. Preclinical efficacy of the camptothecin–polymer conjugate IT-101 in multiple cancer models. Clin. Cancer Res. 12, 1606–1614 (2006).

Nemunaitis, J. et al. Phase I study of CT-2103, a polymer-conjugated paclitaxel, and carboplatin in patients with advanced solid tumors. Cancer Invest. 23, 671–676 (2005).

Seymour, L. W. et al. Hepatic drug targeting: Phase I evaluation of polymer bound doxorubicin. J. Clin. Oncol. 20, 1668–1676 (2002).

Julyan, P. J. et al. Preliminary clinical study of the distribution of HPMA copolymer-doxorubicin bearing galactosamine. J. Control. Release 57, 281–290 (1999).

Heidel, J. D. 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 104, 5715–5721 (2007).

Zhou, Y. et al. Impact of single-chain Fv antibody fragment affinity on nanoparticle targeting of epidermal growth factor receptor-expressing tumor cells. J. Mol. Biol. 371, 934–947 (2007).

Gottesman, M. M. Mechanisms of cancer drug resistance. Annu. Rev. Med. 53, 615–627 (2002).

Gottesman, M. M., Fojo, T. & Bates, S. E. Multidrug resistance in cancer: role of ATP-dependent transporters. Nature Rev. Cancer 2, 48–58 (2002).

Modok, S., Mellor, H. R. & Callaghan, R. Modulation of multidrug resistance efflux pump activity to overcome chemoresistance in cancer. Curr. Opin. Pharmacol. 6, 350–354 (2006).

Nobili, S., Landini, I., Giglioni, B. & Mini, E. Pharmacological strategies for overcoming multidrug resistance. Curr. Drug Targets 7, 861–879 (2006).

Thomas, H. & Coley, H. M. Overcoming multidrug resistance in cancer: an update on the clinical strategy of inhibiting p-glycoprotein. Cancer Control 10, 159–165 (2003).

Pepin, X. 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. 702, 181–191 (1997).

Vauthier, C., Dubernet, C., Chauvierre, C., Brigger, I. & Couvreur, P. Drug delivery to resistant tumors: the potential of poly(alkyl cyanoacrylate) nanoparticles. J. Control. Release 93, 151–160 (2003).

Peracchia, M. T. et al. Stealth PEGylated polycyanoacrylate nanoparticles for intravenous administration and splenic targeting. J. Control. Release 60, 121–128 (1999).

Lee, E. S., Na, K. & Bae, Y. H. Doxorubicin loaded pH-sensitive polymeric micelles for reversal of resistant MCF-7 tumor. J. Control. Release 103, 405–418 (2005).

Sahoo, S. K., Ma, W. & Labhasetwar, V. Efficacy of transferrin-conjugated paclitaxel-loaded nanoparticles in a murine model of prostate cancer. Int. J. Cancer 112, 335–340 (2004).

Suzuki, R. et al. Effective anti-tumor activity of oxaliplatin encapsulated in transferrin-PEG-liposome. Int. J. Pharm. 346, 143–150 (2008).

Northfelt, D. W. et al. Efficacy of pegylated-liposomal doxorubicin in the treatment of AIDS-related Kaposi's sarcoma after failure of standard chemotherapy. J. Clin. Oncol. 15, 653–659 (1997).

Li, C. & Wallace, S. Polymer–drug conjugates: recent development in clinical oncology. Adv. Drug Del. Rev. 60, 886–898 (2008).

Matsumura, Y. Poly(amino acid) micelle nanocarriers in preclinical and clinical studies. Adv. Drug Del. Rev. 60, 899–914 (2008).

Gardner, E. R. et al. Randomized crossover pharmacokinetic study of solvent-based paclitaxel and nab-paclitaxel. Clin. Cancer Res. 14, 4200–4205 (2008).

Lockman, P. R., Koziara, J. M., Mumper, R. J. & Allen, D. D. Nanoparticle surface charges alter blood–brain barrier integrity and permeability. J. Drug Target. 12, 635–641 (2004).

Kim, J. S. et al. Toxicity and tissue distribution of magnetic nanoparticles in mice. Toxicol. Sci. 89, 338–347 (2006).

Salvador-Morales, C. Complement activation and protein adsorption by carbon nanotubes. Mol. Immunol. 43, 193–201 (2006).

Wang, X., Yang, L., Chen, Z. G. & Shin, D. M. Application of nanotechnology in cancer therapy and imaging. CA Cancer J. Clin. 58, 97–110 (2008).

Qian, X. et al. In vivo tumor targeting and spectroscopic detection with surface-enhanced Raman nanoparticle tags. Nature Biotech. 26, 83–90 (2008).

Cho, K., Wang X., Nie, S., Chen Z.G. & Shin, D. M. Therapeutic nanoparticles for drug delivery in cancer. Clin. Cancer Res. 14, 1310–1316 (2008).

Schluep, T. et al. Pharmacokinetics and biodistribution of the camptohecin-polymer conjugate IT-101 in rats and tumor-bearing mice. Cancer Chemother. Pharmacol. 57, 654–662 (2006).

Pfizer. CAMPTOSAR U.S. Physician Prescribing Information. Pfizer web site [online], (2008).

Herben, V. M., ten Bokkel Huinink, W. W. & Beijnen, J. H. Clinical pharmacokinetics of topotecan. Clin. Pharmacokinet. 31, 85–102 (1996).

Kraut, E. H. et al. Final results of a phase I study of liposome encapsulated SN-38 (LE-SN38): safety, pharmacogenomics, pharmacokinetics, and tumor response. J. Clin. Oncol. 23 (Suppl. 16), 2017 (2005).

Daud, A. et al. Phase I trial of CT-2106 (polyglutamated camptothecin) administered weekly in patients with advanced solid tumor malignancies. J. Clin. Oncol. 24 (Suppl. 18), 2015 (2006).

Bross, P. F. et al. Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin. Cancer Res. 7, 1490–1496 (2001).

Kawakami, K., Nakajima, O., Morishita, R. & Nagai, R. Targeted anticancer immunotoxins and cytotoxic agents with direct killing moieties. ScientificWorldJournal 6, 781–790 (2006).

Allen, T. M. Ligand-targeted therapeutics in anticancer therapy. Nature Rev. Cancer 2, 750–763 (2002).

Duncan, R. Polymer conjugates as anticancer nanomedicines. Nature Rev. Cancer 6, 688–701 (2006).

Matsumura, M. et al. Phase I and pharmacokinetic study of MCC-465, a doxorubicin (DXR) encapsulated in PEG immunoliposome, in patients with metastatic stomach cancer. Ann. Oncol. 15, 517–525 (2004).

MedBiopharm Co., Ltd. Safety study of MBP-426 (liposomal oxaliplatin suspension for injection) to treat advanced or metastatic solid tumors. ClinicalTrials.gov web site [online], (2008).

Phan, A. et al. Open label phase I study of MBP-426, a novel formulation of oxalipatin, in patients with advanced or metastatic solid tumors. Proc. AACR-NCI-EORTC Int. Conf. Mol. Targets Cancer Therapeut. Discov. Develop. Clin. Valid. Abstract C115 (2007).

SynerGene Therapeutics, Inc. Safety Study of Infusion of SGT-53 to Treat Solid Tumors. ClinicalTrials.gov web site [online], (2008).

Calando Pharmaceuticals. Safety Study of CALAA-01 to Treat Solid Tumor Cancers. ClinicalTrials.gov web site [online], (2008).