Current state, achievements, and future prospects of polymeric micelles as nanocarriers for drug and gene delivery

Pharmacology & Therapeutics - Tập 112 - Trang 630-648 - 2006
Nobuhiro Nishiyama1,2, Kazunori Kataoka1,3,2
1Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
2Center for NanoBio Integration, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan
3Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan

Tài liệu tham khảo

Allen, 1991, Pharmacokinetics of stealth versus conventional liposomes: effect of dose, Biochim Biophys Acta, 1068, 133, 10.1016/0005-2736(91)90201-I Allen, 1999, Nano-engineering block copolymer aggregates for drug delivery, Colloids Surf B Biointerfaces, 16, 3, 10.1016/S0927-7765(99)00058-2 Bae, 2003, Design of environment-sensitive supramolecular assemblies for intracellular drug delivery: polymeric micelles that are responsive to intracellular pH change, Angew Chem Int Ed, 42, 4640, 10.1002/anie.200250653 Bae, 2005, Preparation and biological characterization of polymeric micelle drug carriers with intracellular pH-triggered drug release property: tumor permeability, controlled subcellular drug distribution, and enhanced in vivo antitumor efficacy, Bioconjug Chem, 16, 122, 10.1021/bc0498166 Bae, 2005, Multifunctional polymeric micelles with folate-mediated cancer cell targeting and pH-triggered drug releasing properties for active intracellular drug delivery, Mol Biosyst, 1, 242, 10.1039/b500266d Batrakova, 2001, Mechanism of sensitization of MDR cancer cells by Pluronic block copolymers: selective energy depletion, Br J Cancer, 85, 1987, 10.1054/bjoc.2001.2165 Behr, 1997, The proton sponge. A trick to enter cells the viruses did not exploit, Chimia, 51, 34, 10.2533/chimia.1997.34 Berg, 1999, Photochemical internalization: a novel technology for delivery of macromolecules into cytosol, Cancer Res, 59, 1180 Boeckle, 2004, Purification of polyethylenimine polyplexes highlights the role of free polycations in gene transfer, J Gene Med, 6, 1102, 10.1002/jgm.598 Cabral, 2005, Preparation and biological properties of dichloro(1,2-diaminocyclohexane)platinum(II) (DACHPt)-loaded polymeric micelles, J Control Release, 101, 223, 10.1016/j.jconrel.2004.08.022 Chau, 2003, Oxaliplatin for colorectal cancer in the United States: better late than never, J Clin Oncol, 21, 2049, 10.1200/JCO.2003.03.074 Clapham, 1995, Calcium signaling, Cell, 80, 259, 10.1016/0092-8674(95)90408-5 Derycke, 2004, Liposomes for photodynamic therapy, Adv Drug Deliv Rev, 56, 17, 10.1016/j.addr.2003.07.014 Dougherty, 1998, Photodynamic therapy, J Natl Cancer Inst, 90, 889, 10.1093/jnci/90.12.889 Duncan, 2003, The dawning era of polymer therapeutics, Nat Rev Drug Discov, 2, 347, 10.1038/nrd1088 Dvorak, 1995, Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis, Am J Pathol, 146, 1029 Elbashir, 2001, Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells, Nature, 411, 494, 10.1038/35078107 Ferrari, 2005, Cancer nanotechnology: opportunities and challenges, Nat Rev Cancer, 5, 161, 10.1038/nrc1566 Fukushima, 2005, PEGylated polyplex micelles from triblock catiomers with spatially ordered layering of condensed pDNA and buffering units for enhanced intracellular gene delivery, J Am Chem Soc, 127, 2810, 10.1021/ja0440506 Gianasi, 1999, HPMA copolymer platinates as novel antitumor agents: in vitro properties, pharmacokinetics and antitumor activity in vivo, Eur J Cancer, 35, 994, 10.1016/S0959-8049(99)00030-1 Gordon, 2001, Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin vs. topotecan, J Clin Oncol, 19, 3312, 10.1200/JCO.2001.19.14.3312 Gref, 1994, Biodegradable long-circulating polymeric nanospheres, Science, 263, 1600, 10.1126/science.8128245 Grossweiner, 1982, Type I and type II mechanisms in the photosensitized lysis of phosphatidylcholine liposomes by hematoporphyrin, Photochem Photobiol, 36, 159, 10.1111/j.1751-1097.1982.tb04358.x Hamaguchi, 2005, NK105, a paclitaxel-incorporating micellar nanoparticle formulation, can extend in vivo antitumor activity and reduce the neurotoxicity of paclitaxel, Br J Cancer, 92, 1240, 10.1038/sj.bjc.6602479 Hamilton, 1998, Multicellular spheroids as an in vitro tumor model, Cancer Lett, 131, 29, 10.1016/S0304-3835(98)00198-0 Harada, 1995, Formation of polyion complex micelles in aqueous milieu from a pair of oppositely-charged block copolymers with poly(ethylene glycol) segments, Macromolecules, 28, 5294, 10.1021/ma00119a019 Harada, 1999, Chain length recognition: core–shell supermolecular assembly from oppositely charged block copolymers, Science, 283, 65, 10.1126/science.283.5398.65 Harada-Shiba, 2002, Polyion complex micelles as vectors in gene therapy - pharmacokinetics and in vivo gene transfer, Gene Ther, 9, 407, 10.1038/sj.gt.3301665 Hobbs, 1998, Regulation of transport pathways in tumor vessels: role of tumor type and microenvironment, Proc Natl Acad Sci U S A, 95, 4607, 10.1073/pnas.95.8.4607 Høgset, 2000, Photochemical transfection: a new technology for light-induced, site-directed gene delivery, Hum Gene Ther, 11, 869, 10.1089/10430340050015482 Høgset, 2002, Photochemical transfection: a technology for efficient light-directed gene delivery, Somat Cell Mol Genet, 27, 97, 10.1023/A:1022979806314 Høgset, 2004, Photochemical internalization in drug and gene delivery, Adv Drug Deliv Rev, 56, 95, 10.1016/j.addr.2003.08.016 Ideta, 2005, Nanotechnology-based photodynamic therapy for neovascular disease using a supramolecular nanocarrier loaded with a dendritic photosensitizer, Nano Lett, 5, 2426, 10.1021/nl051679d Itaka, 2002, Evaluation by fluorescence resonance energy transfer of the stability of nonviral gene delivery vectors under physiological conditions, Biomacromolecules, 3, 841, 10.1021/bm025527d Itaka, 2003, Polyion complex micelles from plasmid DNA and poly(ethylene glycol)–poly(l-lysine) block copolymer as serum-tolerable polyplex system: physiological properties of micelles relevant to gene transfection efficiency, Biomaterials, 24, 4495, 10.1016/S0142-9612(03)00347-8 Itaka, 2004, Supramolecular nanocarrier of siRNA from PEG-based block catiomer carrying diamine side chain with distinctive pKa directed to enhance intracellular gene silencing, J Am Chem Soc, 126, 13612, 10.1021/ja047174r Jain, 2001, Delivery of molecular and cellular medicine to solid tumors, Adv Drug Deliv Rev, 46, 149, 10.1016/S0169-409X(00)00131-9 Jang, 2005, Supramolecular nanocarrier of anionic dendrimer porphyrins with cationic block copolymers modified with polyethylene glycol to enhance intracellular photodynamic efficacy, Angew Chem Int Ed, 44, 419, 10.1002/anie.200461603 Jeon, 1991, Protein-surface interactions in the presence of polyethylene oxide: I. Simplified theory, J Colloid Interface Sci, 142, 149, 10.1016/0021-9797(91)90043-8 Jeong, 1998, Clonazepam release from core–shell type nanoparticles in vitro, J Control Release, 51, 169, 10.1016/S0168-3659(97)00163-6 Kabanov, 2005, Polymer genomics: shifting the gene and drug delivery paradigm, J Control Release, 101, 259, 10.1016/j.jconrel.2004.07.009 Kakizawa, 1999, Environment-sensitive stabilization of core–shell structured polyion complex micelle by reversible cross-linking of the core through disulfide bond, J Am Chem Soc, 121, 11247, 10.1021/ja993057y Kakizawa, 2004, Size-controlled formation of a calcium phosphate-based organic-inorganic hybrid vector for gene delivery using poly(ethylene glycol)-block-poly(aspartic acid), Adv Mater, 16, 699, 10.1002/adma.200305782 Kakizawa, 2004, Block copolymer-coated calcium-phosphate nanoparticles sensing intracellular environment for oligodeoxynucleotide and siRNA delivery, J Control Release, 97, 345, 10.1016/j.jconrel.2004.03.031 Kataoka, 1993, Block copolymer micelles as vehicles for drug delivery, J Control Release, 24, 119, 10.1016/0168-3659(93)90172-2 Kataoka, 1996, Targetable polymeric drugs (Chap. 4) Kataoka, 1996, Spontaneous formation of polyion complex micelles with narrow distribution from antisense oligonucleotide and cationic block copolymer in physiological saline, Macromolecules, 29, 8556, 10.1021/ma961217+ Kataoka, 2001, Block copolymer micelles for drug delivery: design, characterization and biological significance, Adv Drug Deliv Rev, 47, 113, 10.1016/S0169-409X(00)00124-1 Katayama, 2001, A polymer micelle responding to the protein kinase A signal, Macromolecules, 34, 8569, 10.1021/ma010966a Katayose, 1997, Water-soluble polyion complex associates of DNA and poly(ethylene glycol)–p(l-lysine) block copolymer, Bioconjug Chem, 8, 702, 10.1021/bc9701306 Kohn, 1992, Pathways of macromolecular tracer transport across venules and small veins, Lab Invest, 67, 596 Kohori, 1999, Control of adriamycin cytotoxic activity using thermally responsive polymeric micelles composed of poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-poly(d,l-lactide), Colloids Surf B Biointerfaces, 16, 195, 10.1016/S0927-7765(99)00070-3 Konerding, 2001, 3D microvascular architecture of pre-cancerous lesions and invasive carcinomas of the colon, Br J Cancer, 84, 1354, 10.1054/bjoc.2001.1809 Kwon, 1994, Enhanced tumor accumulation and prolonged circulation times of micelle-forming poly(ethylene oxide-aspartate) block copolymer-Adriamycin conjugate, J Control Release, 29, 17, 10.1016/0168-3659(94)90118-X La, 1996, Preparation and characterization of the micelle-forming polymeric drug: Indomethacin-incorporated poly(ethylene oxide)–poly(β-benzyl l-aspartate) block copolymer micelles, J Pharm Sci, 85, 85, 10.1021/js950204r Lavasanifar, 2000, Micelles of poly(ethylene oxide)-block-poly(N-alkyl stearate l-aspartamide): synthetic analogues of lipoproteins for drug delivery, J Biomed Mater Res, 52, 831, 10.1002/1097-4636(20001215)52:4<831::AID-JBM29>3.0.CO;2-K Lavasanifar, 2002, Poly(ethylene oxide)-block-poly(l-amino acid) micelles for drug delivery, Adv Drug Deliv Rev, 54, 169, 10.1016/S0169-409X(02)00015-7 Le Garrec, 2002, Optimizing pH-responsive polymeric micelles for drug delivery in a cancer photodynamic therapy model, J Drug Target, 10, 429, 10.1080/1061186021000001887 Lukyanov, 2004, Increased accumulation of PEG–PE micelles in the area of experimental myocardial infarction in rabbits, J Control Release, 4, 187, 10.1016/j.jconrel.2003.10.008 Lee, 2003, Polymeric micelle for tumor pH and folate-mediated targeting, J Control Release, 91, 103, 10.1016/S0168-3659(03)00239-6 Lemieux, 2000, A combination of poloxamers increases gene expression of plasmid DNA in skeletal muscle, Gene Ther, 7, 986, 10.1038/sj.gt.3301189 Lewin, 2000, Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells, Nat Biotechnol, 18, 410, 10.1038/74464 Liu, 2001, Nanostructured materials designed for cell binding and transduction, Biomacromolecules, 2, 362, 10.1021/bm015515c Macdonald, 2001, Basic principle of photodynamic therapy, J Porphyr Phthalocyanines, 5, 105, 10.1002/jpp.328 Maeda, 2001, SMANCS and polymer-conjugated macromolecular drugs: advantages in cancer chemotherapy, Adv Drug Deliv Rev, 46, 169, 10.1016/S0169-409X(00)00134-4 Maruyama, 1999, Possibility of active targeting to tumor tissues with liposomes, Adv Drug Deliv Rev, 40, 89, 10.1016/S0169-409X(99)00042-3 Matsumura, 1986, A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent Smancs, Cancer Res, 46, 6387 Matsumura, 2004, Phase I clinical trial and pharmacokinetic evaluation of NK911, micelle-encapsulated doxorubicin, Br J Cancer, 91, 1775, 10.1038/sj.bjc.6602204 McKeage, 2005, New-generation platinum drugs in the treatment of cisplatin-resistant cancers, Expert Opin Investig Drugs, 14, 1033, 10.1517/13543784.14.8.1033 Merdan, 2003, Pegylated polyethylenimine-Fab′ antibody fragment conjugates for targeted gene delivery to human ovarian carcinoma cells, Bioconjug Chem, 14, 989, 10.1021/bc0340767 Minko, 1999, Comparison of the anticancer effect of free and HPMA copolymer-bound adriamycin in human ovarian carcinoma cells, Pharm Res, 16, 986, 10.1023/A:1018959029186 Minko, 2000, Efficacy of the chemotherapeutic action of HPMA copolymer-bound doxorubicin in a solid tumor model of ovarian carcinoma, Int J Cancer, 86, 108, 10.1002/(SICI)1097-0215(20000401)86:1<108::AID-IJC17>3.0.CO;2-8 Minko, 2005, Pluronic block copolymers alter apoptoric signal transduction of doxorubicin in drug-resistant cancer cells, J Control Release, 105, 269, 10.1016/j.jconrel.2005.03.019 Miyamoto, 1990, Comparison of the cytotoxic effects of the high-and low-molecular weight anticancer agents on multidrug-resistant Chinese hamster ovary cells in vitro, Cancer Res, 50, 1571 Miyata, 2004, Block catiomer polyplexes with regulated densities of charge and disulfide cross-linking directed to enhance gene expression, J Am Chem Soc, 126, 2355, 10.1021/ja0379666 Miyata, 2005, Practically applicable cross-linked polyplex micelle with high tolerability against freeze-drying for in vivo gene delivery, J Control Release, 109, 15, 10.1016/j.jconrel.2005.09.043 Mosqueria, 2001, Relationship between complement activation, cellular uptake and surface physicochemical aspects of novel PEG-modified nanoparticles, Biomaterials, 22, 2967, 10.1016/S0142-9612(01)00043-6 Muggia, 2001, Liposomal encapsulated anthracyclines: new therapeutic horizons, Curr Oncol Rep, 3, 156, 10.1007/s11912-001-0016-5 Muggia, 1996, Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation, J Clin Oncol, 15, 987, 10.1200/JCO.1997.15.3.987 Nagasaki, 2001, Sugar-installed block copolymer micelles: their preparation and specific interaction with lectin molecules, Biomacromolecules, 2, 1067, 10.1021/bm015574q Nah, 2002, Artery wall binding peptide-poly(ethylene glycol)-grafted-poly(l-lysine)-based gene delivery to artery wall cells, J Control Release, 78, 273, 10.1016/S0168-3659(01)00499-0 Neal, 1995, Transcellular gaps in microvascular walls of frog and rat when permeability is increased by perfusion with the ionophore, J Physiol, 488, 427, 10.1113/jphysiol.1995.sp020977 Newman, 1999, Comparative pharmacokinetics, tissue distribution, and therapeutic effectiveness of cisplatin encapsulated in long circulating, pegylated liposomes (SPI-077) in tumor-bearing mice, Cancer Chemother Pharmacol, 43, 1, 10.1007/s002800050855 Nishiyama, 2006, Nanostructured devices based on block copolymer assemblies for drug delivery: designing structures for enhanced drug function, Adv Polym Sci, 193, 67, 10.1007/12_025 Nishiyama, 1999, Preparation and characterization of self-assembled polymer-metal complex micelle from cis-dichlorodiammineplatinum(II) and poly(ethylene glycol)-poly(aspartic acid) block copolymer in an aqueous medium, Langmuir, 15, 377, 10.1021/la980572l Nishiyama, 2001, Cisplatin-loaded polymer-metal complex micelle with time-modulated decaying property as a novel drug delivery system, Pharm Res, 18, 1035, 10.1023/A:1010908916184 Nishiyama, 2003, Light-harvesting ionic dendrimer porphyrins as new photosensitizers for photodynamic therapy, Bioconjug Chem, 14, 58, 10.1021/bc025597h Nishiyama, 2003, Differential gene expression profile between PC-14 cells treated with free cisplatin- and cisplatin-incorporated polymeric micelles, Bioconjug Chem, 14, 449, 10.1021/bc025555t Nishiyama, 2003, Free and N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer-bound geldanamycin derivative induce different stress responses in A2780 human ovarian carcinoma cells, Cancer Res, 63, 7876 Nishiyama, 2003, Novel cisplatin-incorporated polymeric micelles can eradicate solid tumors in mice, Cancer Res, 63, 8977 Nishiyama, 2005, Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer, Nat Mater, 4, 934, 10.1038/nmat1524 Nishiyama, 2005, Smart polymeric micelles for gene and drug delivery, Drug Discov Today Technol, 2, 21, 10.1016/j.ddtec.2005.05.007 Oishi, 2005, Lactosylated poly(ethylene glycol)-siRNA conjugate through acid-labile β-thiopropionate linkage to construct pH-sensitive polyion complex micelles achieving enhanced gene silencing in hepatoma cells, J Am Chem Soc, 127, 1624, 10.1021/ja044941d Omelyanenko, 1998, Targetable HPMA copolymer-adriamycin conjugates. Recognition, internalization, and subcellular fate, J Control Release, 53, 25, 10.1016/S0168-3659(97)00235-6 Pack, 2005, Design and development of polymers for gene delivery, Nat Rev Drug Discov, 4, 581, 10.1038/nrd1775 Prasmickaite, 2001, Evaluation of different photosensitizers for use in photochemical gene transfection, Photochem Photobiol, 73, 388, 10.1562/0031-8655(2001)073<0388:EODPFU>2.0.CO;2 Renno, 2001, Photosensitizer delivery for photodynamic therapy of choroidal neovascularization, Adv Drug Deliv Rev, 52, 63, 10.1016/S0169-409X(01)00195-8 Roberts, 1997, Neovascular induced by vascular endothelial growth factor is fenestrated, Cancer Res, 57, 765 Rosenberg, 1978, Platinum complexes for the treatment of cancer, Interdisc Sci Rev, 3, 134, 10.1179/030801878791926119 Rudolph, 2003, Oligomers of the arginine-rich motif of the HIV-1 TAT protein are capable of transferring plasmid DNA into cells, J Biol Chem, 278, 11411, 10.1074/jbc.M211891200 Savic, 2003, Micellar nanocontainers distribute to defined cytoplasmic organelles, Science, 300, 615, 10.1126/science.1078192 Seymour, 1987, Effect of molecular weight (Mw) of N-(2-hydroxypropyl)methacrylamide copolymers on body distribution and rate of excretion after subcutaneous, intraperitoneal, and intravenous administration to rats, J Biomed Mater Res, 21, 1341, 10.1002/jbm.820211106 Sheff, 2004, Endosomes as a route for drug delivery in the real world, Adv Drug Deliv Rev, 56, 927, 10.1016/j.addr.2003.11.005 Siddik, 1987, The comparative pharmacokinetics of carboplatin and cisplatin in mice and rats, Biochem Pharmacol, 36, 1925, 10.1016/0006-2952(87)90490-4 Stapert, 2000, Polyion complex micelles encapsulating light-harvesting ionic dendirmer zinc porphyrins, Langmuir, 16, 8182, 10.1021/la000423e Stewart, 1998, Randomized comparative trial of pegylated liposomal doxorubicin vs. bleomycin and vincristine in the treatment of AIDS-related Kaposi's sarcoma. International Pegylated Liposomal Doxorubicin Study Group, J Clin Oncol, 16, 683, 10.1200/JCO.1998.16.2.683 Stolnik, 1995, Long circulating microparticulate drug carriers, Adv Drug Deliv Rev, 16, 195, 10.1016/0169-409X(95)00025-3 Sutherland, 1988, Cell and environment interactions in tumor microregions: the multicell spheroid model, Science, 240, 177, 10.1126/science.2451290 2002, Guidelines for using verteporfin (visudyne) in photodynamic therapy to treat choroidal neovascularization due to age-related macular degeneration and other causes, Retina, 22, 6, 10.1097/00006982-200202000-00003 Tijerina, 2003, Mechanism of cyototoxicity in human ovarian carcinoma cells exposed to free Mce6 or HPMA copolymer Mce6 conjugates, Photochem Photobiol, 77, 645, 10.1562/0031-8655(2003)077<0645:MOCIHO>2.0.CO;2 Torchilin, 2002, PEG-based micelles as carriers of contrast agents for different imaging modalities, Adv Drug Deliv Rev, 54, 235, 10.1016/S0169-409X(02)00019-4 Torchilin, 2003, Immunomicelles: targeted pharmaceutical carriers for poorly soluble drugs, Proc Natl Acad Sci U S A, 100, 6039, 10.1073/pnas.0931428100 Tsukioka, 2002, Pharmaceutical and biomedical differences between micellar doxorubicin (NK911) and liposomal doxorubicin (Doxil), Jpn J Cancer Res, 93, 1145, 10.1111/j.1349-7006.2002.tb01217.x Uchino, 2005, Cisplatin-incorporating polymeric micelles (NC-6004) can reduce nephrotoxicity and neurotoxicity of cisplatin in rats, Br J Cancer, 93, 678, 10.1038/sj.bjc.6602772 Unezaki, 1996, Direct measurement of the extravasation of polyethylene glycol-coated liposomes into solid tumour tissue by in vivo fluorescence microscopy, Int J Pharmacol, 144, 11, 10.1016/S0378-5173(96)04674-1 Uwatoku, 2003, Application of nanoparticle technology for the prevention of restenosis after balloon injury in rats, Circ Res, 92, e62, 10.1161/01.RES.0000069021.56380.E2 Uziely, 1995, Liposomal doxorubicin: antitumor activity and unique toxicities during two complementary phase I studies, J Clin Oncol, 13, 1777, 10.1200/JCO.1995.13.7.1777 Verma, 1997, Gene therapy—promises, problems and prospects, Nature, 389, 239, 10.1038/38410 Vinogradov, 1999, Polyion complex micelles with protein-modified corona for receptor-mediated delivery of oligonucleotides into cells, Bioconjug Chem, 10, 851, 10.1021/bc990037c Ward, 2001, Systemic circulation of poly(l-lysine)/DNA vectors is influenced by polycation molecular weight and type of DNA: differential circulation in mice and rats and the implications for human gene therapy, Blood, 97, 2221, 10.1182/blood.V97.8.2221 Wakebayashi, 2004, Lactose-conjugated polyion complex micelles incorporating plasmid DNA as a targetable gene vector system: their preparation and gene transfecting efficiency against cultured HepG2 cells, J Control Release, 95, 653, 10.1016/j.jconrel.2004.01.003 Weitman, 1992, Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues, Cancer Res, 52, 3396 Woodle, 1992, Versatility in lipid composition showing prolonged circulation with sterically stabilized liposome, Biochim Biophys Acta, 1105, 193, 10.1016/0005-2736(92)90194-Q Yamamoto, 2001, Long-circulating poly(ethylene glycol)–poly(d,l-lactide) block copolymer micelles with modulated surface charge, J Control Release, 77, 27, 10.1016/S0168-3659(01)00451-5 Yamamoto, 2002, Temperature-related change in the properties relevant to drug delivery of poly(ethylene glycol)–poly(d,l-lactide) block copolymer micelles in aqueous milieu, J Control Release, 82, 359, 10.1016/S0168-3659(02)00147-5 Yokoyama, 1989, Molecular design for missile drugs: synthesis of adriamycin conjugated with immunoglobulin G using poly(ethylene glycol)-block-poly(aspartic acid) as intermediate carrier, Makromol Chem, 190, 2041, 10.1002/macp.1989.021900904 Yokoyama, 1990, Polymer micelles as novel drug carriers: adriamycin-conjugated poly(ethylene glycol)-poly(aspartic acid) block copolymer, J Control Release, 11, 269, 10.1016/0168-3659(90)90139-K Yokoyama, 1990, Characterization and anti-cancer activity of micelle-forming polymeric anti-cancer drug, adriamycin-conjugated poly(ethylene glycol)–poly(aspartic acid) block copolymer, Cancer Res, 50, 1693 Yokoyama, 1991, Toxicity and antitumor activity against solid tumors of micelle-forming polymeric anticancer drug and its extremely long circulation in blood, Cancer Res, 51, 3229 Yokoyama, 1993, Analysis of micelle formation of an adriamycin-conjugated poly(ethylene glycol)–poly(aspartic acid) block copolymer by gel permeation chromatography, Pharm Res, 10, 895, 10.1023/A:1018921513605 Yokoyama, 1994, Improved synthesis of adriamycin-conjugated poly(ethylene glycol)–poly(aspartic acid) block copolymer and formation of unimodal micellar structure with controlled amount of physically entrapped adriamycin, J Control Release, 32, 269, 10.1016/0168-3659(94)90237-2 Yokoyama, 1998, Incorporation of water-insoluble anticancer drug into polymeric micelles and control of their particle size, J Control Release, 55, 219, 10.1016/S0168-3659(98)00054-6 Yokoyama, 1999, Selective delivery of adriamycin to a solid tumor using a polymeric micelle carrier system, J Drug Target, 7, 171, 10.3109/10611869909085500 Yuan, 1996, Time-dependent vascular regression and permeability changes in established human tumor xenografts induced by an anti-vascular endothelial growth factor/vascular permeability factor antibody, Proc Natl Acad Sci U S A, 93, 14765, 10.1073/pnas.93.25.14765