Improved Tumor Targeting of Polymer-Based Nanovesicles Using Polymer鈥揕ipid Blends

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• 作者：Zhiliang Cheng ; Drew R. Elias ; Neha P. Kamat ; Eric D. Johnston ; Andrei Poloukhtine ; Vladimir Popik ; Daniel A. Hammer ; Andrew Tsourkas
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：October 19, 2011
• 年：2011
• 卷：22
• 期：10
• 页码：2021-2029
• 全文大小：981K
• 年卷期：v.22,no.10(October 19, 2011)
• ISSN：1520-4812

文摘

Block copolymer-based vesicles have recently garnered a great deal of interest as nanoplatforms for drug delivery and molecular imaging applications due to their unique structural properties. These nanovesicles have been shown to direct their cargo to disease sites either through enhanced permeability and retention or even more efficiently via active targeting. Here, we show that the efficacy of nanovesicle targeting can be significantly improved when prepared from polymer鈥搇ipid blends compared with block copolymer alone. Polymer鈥搇ipid hybrid nanovesicles were produced from the aqueous coassembly of the diblock copolymer, poly(ethylene oxide)-block-polybutadiene (PEO-PBD), and the phospholipid, hydrogenated soy phosphatidylcholine (HSPC). The PEG-based vesicles, 117 nm in diameter, were functionalized with either folic acid or anti-HER2/neu affibodies as targeting ligands to confer specificity for cancer cells. Our results revealed that nanovesicles prepared from polymer鈥搇ipid blends led to significant improvement in cell binding compared to nanovesicles prepared from block copolymer alone in both in vitro cell studies and murine tumor models. Therefore, it is envisioned that nanovesicles composed of polymer鈥搇ipid blends may constitute a preferred embodiment for targeted drug delivery and molecular imaging applications.