期刊
ACS NANO
卷 7, 期 10, 页码 8583-8592出版社
AMER CHEMICAL SOC
DOI: 10.1021/nn402662d
关键词
drug delivery; block copolymer; polymeric micelle; integrin; cRGD; cancer therapy
类别
资金
- Funding Program for World-Leading Innovative R&D on Science and Technology (FIRST Program) from the Japan Society for the Promotion of Science (JSPS)
- Japanese Ministry of Health, Labour and Welfare (MHLW)
- JSPS
- Grants-in-Aid for Scientific Research [23790043, 24689051, 24390340, 25293273, 25670010, 24659584, 13F03042, 23390009, 25750172] Funding Source: KAKEN
Ligand-mediated drug delivery systems have enormous potential for improving the efficacy of cancer treatment. In particular, Arg-Gly-Asp peptides are promising ligand molecules for targeting alpha(gamma),beta(3)/alpha(gamma)beta(5) integrins, which are overexpressed in angiogenic sites and tumors, such as intractable human glioblastoma (U87MG). We here achieved highly efficient drug delivery to U87MG tumors by using a platinum anticancer drug-incorporating polymeric micelle (PM) with cyclic Arg-Gly-Asp (cRGD) ligand molecules. Intravital confocal laser scanning microscopy revealed that the cRGD-linked polymeric micelles (cRGD/m) accumulated rapidly and had high permeability from vessels into the tumor parenchyma compared with the PM having nontargeted ligand, cyclic-Arg-Ala-Asp (cRAD). As both cRGD/m- and cRAD-linked polymeric micelles have similar characteristics, including their size, surface charge, and the amount of incorporated drugs, it is likely that the selective and accelerated accumulation of cRGD/m into tumors occurred via an active internalization pathway, possibly transcytosis, thereby producing significant antitumor effects in an orthotopic mouse model of U87MG human glioblastoma.
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