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Improved tumor targeting of polymer-based nanovesicles using polymer-lipid blends.

Bioconjugate chemistry (2011-09-09)
Zhiliang Cheng, Drew R Elias, Neha P Kamat, Eric D Johnston, Andrei Poloukhtine, Vladimir Popik, Daniel A Hammer, Andrew Tsourkas

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-lipid blends compared with block copolymer alone. Polymer-lipid 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-lipid 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-lipid blends may constitute a preferred embodiment for targeted drug delivery and molecular imaging applications.

Product Number
Product Description

Polybutadiene, average Mw ~200,000
Polybutadiene, predominantly 1,2-addition, approx. 90% 1,2-vinyl
Polybutadiene, average Mn ~5,000
Polybutadiene, cis, average Mw 200,000-300,000
Polybutadiene, average Mn 1,530-2,070 by VPO
Atto 740 maleimide, suitable for fluorescence
Atto 740-Biotin, suitable for fluorescence, ≥90.0% (HPCE)
Atto 740 NHS ester, BioReagent, suitable for fluorescence, ≥90.0% (coupling to amines)

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