Trastuzumab-functionalized nanoparticles of biodegradable copolymers for targeted delivery of docetaxel.
OBJECTIVE
We synthesized a novel system of docetaxel-loaded, trastuzumab-functionalized nanoparticles (NPs) of biodegradable copolymers for targeted and synergistic chemotherapy.


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.


CONCLUSIONS
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.
Sun
Bingfeng
B
Division of Bioengineering, National University of Singapore, Singapore.
Feng
Si-Shen
SS
D000911:Antibodies, Monoclonal / Q000737:chemistry*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D011108:Polymers / Q000737:chemistry*; D043823:Taxoids / Q000008:administration & dosage* / Q000494:pharmacology; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D004337:Drug Carriers; D011108:Polymers; D043823:Taxoids; D000077143:Docetaxel; D000068878:Trastuzumab