Trastuzumab-Functionalized Nanoparticles of Biodegradable Copolymers for Targeted Delivery of Docetaxel
Authors:
- 8 June 2009
- journal article
- research article
- Published by Taylor & Francis in Nanomedicine
- Vol. 4 (4) , 431-445
Abstract
We synthesized a novel system of docetaxel-loaded, trastuzumab-functionalized nanoparticles (NPs) of biodegradable copolymers for targeted and synergistic chemotherapy. NPs of two component biodegradable copolymers were prepared by a modified solvent extraction/evaporation method with D-alpha-tocopheryl polyethylene glycol succinate (TPGS) as emulsifier. One component copolymer is poly(lactide)-TPGS, which is of desired hydrophobic-lipophilic balance for cellular adhesion, and another is carboxyl group-terminated TPGS, which facilitates the conjugation of trastuzumab on the NP surface for targeting. In vitro investigation with SK-BR-3 breast cancer cells of HER2 overexpression showed that the trastuzumab-functionalized NPs have great advantages over nude NPs in cellular uptake and cytotoxicity. Trastuzumab conjugated onto the NP surface has two functions: one is to target HER2-overexpressing cancer cells and the other is to enhance the cytotoxicity of docetaxel through synergistic effects. The trastuzumab-functionalized, docetaxel-loaded NPs have great potential for targeted chemotherapy to treat HER2-overexpressing cancer.Keywords
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