Evaluation of HER2 Targeted Poly(Ethylene Glycol)‐Poly( L ‐histidine) Copolymer Micelles in Breast Cancer Models

Résumé fourni par la source

Breast cancer positive for human epidermal growth factor receptor-2 (HER2) is challenging to treat due to the development of drug resistance, even with recently developed antibody-mediated therapeutics. However, nanotechnology provides new innovative therapeutic strategies. This study evaluates the efficacy of new HER2-targeted, pH-sensitive poly(ethylene glycol)-poly(L-histidine) copolymer micelles (PEG-PHis micelles), either empty, loaded with the drug doxorubicin (DOX), or the fluorophore Rhodamine-B (RB) for imaging purposes. Cellular association of the micelles, in vitro effects on proliferation and cytotoxicity, as well as ex vivo and in vivo responses on tumor growth are assessed. The results indicate that trastuzumab (TZM) conjugation enhances the specific cellular association of PEG-PHis micelles in HER2 overexpressing cells and improves the cytotoxic effects of the micelles themselves. Although the TZM conjugation of DOX-loaded micelles did not contribute to an enhancement in overall efficacy in cell lines and tumor explant cultures, the findings highlight the potential of TZM conjugation on these micelles in targeting HER2-positive tumors.

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