期刊
JOURNAL OF CONTROLLED RELEASE
卷 102, 期 1, 页码 191-201出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jconrel.2004.09.023
关键词
angiogenesis; HPMA copolymers; targeted delivery; tumor therapy; biodistribution
资金
- NCI NIH HHS [CA 99-015] Funding Source: Medline
- PHS HHS [98-008] Funding Source: Medline
Sites of neovascular angiogenesis are important chemotherapy targets. In this study, the synthesis, characterization, in-vivo imaging and biodistribution of a technetium-99m labeled, water-soluble, N-(2-hydroxypropyl) methacrylamide (HPMA) copolymer carrying doubly cyclized Arg-Gly-Asp motifs (HPMA copolymer-RGD4C conjugate) are reported. In vitro endothelial cell adhesion assays indicated that HPMA copolymer-RGD4C conjugates inhibited alpha(v)beta(3)-mediated endothelial cell adhesion while HPMA copolymer Arg-Gly-Glu control conjugates (HPMA copolymer-RGE4C conjugate) and hydrolyzed HPMA copolymer precursor (HPMA copolymer) showed no activity. The scintigraphic images of prostate tumor bearing SCID mice obtained 24 h post-i.v. injection indicated greater tumor localization of HPMA copolymer-RGD4C conjugate than the control, HPMA copolymer-RGE4C conjugate. The 24-h necropsy radioactivity data showed that HPMA copolymer-RGD4C conjugate had significantly higher (p<0.001) tumor localization compared to HPMA copolymer-RGE4C conjugate and HPMA copolymer. Also, HPMA copolymer-RGD4C conjugates had sustained tumor retention over 72 h and reasonably efficient clearance from the background organs. These results suggest that specific tumor angiogenesis targeting is possible with HPMA copolymer-RGD4C conjugates. This construct provides a foundation that should support targeted delivery of radionuclides and drugs to solid tumors for diagnostic and therapeutic applications. (C) 2004 Elsevier B.V. All rights reserved.
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