期刊
ADVANCED DRUG DELIVERY REVIEWS
卷 62, 期 2, 页码 167-183出版社
ELSEVIER
DOI: 10.1016/j.addr.2009.11.027
关键词
N-(2-hydroxypropyl) methacrylamide (HPMA); RGDfK; RGD4C; Tumor targeting; Angiogenesis
资金
- National Institutes of Health [R01 EB007171]
This review describes the design and development of N-(2-hydroxypropyl)-methacrylamide (HPMA) copolymer-cyclic RGD conjugates for targeting tumor angiogenesis. Relative to non-targetable systems, HPMA copolymer-RGD4C and -RGDfK conjugates have shown increased tumor accumulation in a variety of solid tumors including prostate, lung, and breast tumor xenografts. Compared to free peptides, copolymers had increased tumor accumulation and decreased uptake in non-target organs such as the liver and spleen. Clinically relevant imaging agents such as Tc-99m, In-111, and Gd enabled in vivo imaging of the constructs by scintigraphy and magnetic resonance techniques. Targeted delivery of Y-90, a radiotherapeutic agent by HPMA copolymer-RGD4C conjugates resulted in tumor size reduction in mice bearing prostate tumor xenografts. Delivery of the geldanamycin derivative 17-(6-aminohexylamino)-17-demethoxygeldanamycin by HPMA copolymer-RGDfK conjugates resulted in increased tumor concentration of the free drug in a prostate xenograft model. These constructs show promise for targeted delivery of therapeutics and imaging agents to solid tumors. (C) 2009 Elsevier B.V. All rights reserved
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