Bingfeng Sun1, Si-Shen Feng. 1. Division of Bioengineering, National University of Singapore, Singapore.
Abstract
AIMS: We synthesized a novel system of docetaxel-loaded, trastuzumab-functionalized nanoparticles (NPs) of biodegradable copolymers for targeted and synergistic chemotherapy. MATERIALS & METHODS: 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. RESULTS: 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. CONCLUSION: 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.
AIMS: We synthesized a novel system of docetaxel-loaded, trastuzumab-functionalized nanoparticles (NPs) of biodegradable copolymers for targeted and synergistic chemotherapy. MATERIALS & METHODS: 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. RESULTS: 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. CONCLUSION: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.
Authors: Michael E Werner; Jonathan A Copp; Shrirang Karve; Natalie D Cummings; Rohit Sukumar; Chenxi Li; Mary E Napier; Ronald C Chen; Adrienne D Cox; Andrew Z Wang Journal: ACS Nano Date: 2011-10-28 Impact factor: 15.881