Targeted intracellular codelivery of chemotherapeutics and nucleic acid with a well-defined dendrimer-based nanoglobular carrier

被引：169

作者：

Kaneshiro, Todd L. ^{[1
]}

Lu, Zheng-Rong ^{[1
]}

机构：

[1] Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84108 USA

来源：

BIOMATERIALS | 2009年 / 30卷 / 29期

关键词：

Codelivery; Nanoglobules; Doxorubicin; siRNA; OVARIAN-CARCINOMA CELLS; BIOLOGICAL EVALUATION; GENE-THERAPY; IN-VITRO; DELIVERY; DOXORUBICIN; COPOLYMER; TUMOR; NANOPARTICLES; CANCER;

D O I：

10.1016/j.biomaterials.2009.06.026

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Codelivery of different therapeutics has a potential to efficaciously treat human diseases via their synergetic effects. We have recently developed a new class dendrimers, poly(L-lysine) dendrimers with a silsesquioxane cubic core (nanoglobules). These dendrimers have compact globular and well-defined structures and highly functionalized surfaces, and can be used as versatile carriers for biomedical applications. In this study, a generation-3 (G3) nanoglobular dendrimer was used to conjugate a peptide c(RGDfK) with a PEG spacer for codelivery of doxorubicin (DOX) and siRNA. Doxorubicin (DOX) was coupled to the RGD targeted nanoglobule via a degradable disulfide spacer to give G3-[PEG-RGD]-[DOX]. G3-[PEG-RGD]-[DOX] showed higher cytotoxicity than free DOX at high doses in glioblastoma U87 cells. G3-[PEG-RGD]-[DOX] was further complexed with siRNA and such complexes were readily internalized by U87 cells as shown by confocal microscopy. The siRNA complexes of the targeted conjugate resulted in significantly higher gene silencing efficiency in U87-Luc cells than those of control conjugates G3-[PEG-RGD] and G3-[DOX]. The nanoglobules are promising carriers for the codelivery of nucleic acids and chemotherapeutic agents. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：5660 / 5666

页数：7

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