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Targeted nanoparticle-polypeptide bioconjugates for breast cancer therapy

Abstract:

Novel approaches that allow for a more effective and less toxic chemotherapy for disseminated breast cancer are needed for which the current therapies are largely ineffective. We report the development of controlled release polymer nanoparticles using a poly (D,L lactic)-poly(ethylene glycol) copolymer with a terminal maleimide functional group (PLA-PEG-MAL). These nanoparticles were conjugated to a polypeptide sequence that has preferential binding characteristics for the Her-2 receptor, a well characterized antigen that is over-expressed on the surface of breast cancers. The conjugation of the peptide does not affect the physical properties of the nanoparticles and we did not observe any nanoparticle aggregation. We next demonstrated a differential cytotoxity of these bioconjugates using docetaxel encapsulated targeted nanoparticles. These bioconjugates specifically bound to and were taken up by the Her2 expressing cells resulting in enhanced differential cytotoxity to empty nanoparticle controls. These targeted drug delivery nanoparticles could be used as a powerful therapeutic tool for Her2 expressing cancers.