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In this study, we aimed to develop anti-human epidermal growth factor receptor 2 (HER2) indocyanine green (ICG)-doxorubicin (DOX)-encapsulated polyethylene glycol-poly(lactic-co-glycolic acid) diblock copolymeric nanoparticles (HIDPPNPs) to explore the co-administration of phototherapy and chemotherapy for HER2-overexpressing breast cancer, a highly aggressive and medicine-resistant breast carcinoma. The HIDPPNPs were fabricated using a solvent evaporation technique followed by carbodiimide-mediated antibody conjugation on the nanoparticle surface. Compared with freely dissolved ICG, the HIDPPNPs conferred enhanced thermal stability to the entrapped ICG, were able to generate a hyperthermia effect at concentrations ≥1 μM ICG equivalent and provided increased production of singlet oxygen under 808-nm laser irradiation with an intensity of 6 W/cm2. Furthermore, the uptake efficiency of the HIDPPNPs in MDA-MB-453/HER2(+) cells was approximately 2-fold higher than that in MCF7/HER2(-) cells, demonstrating that the HIDPPNPs specifically target HER2- expressing cells. Based on the viability analysis, the HIDPPNPs exhibited effective cytotoxicity upon light exposure (808 nm; 6 W/cm2), and the resulting cell death rate was even higher than that caused by using twice amount of encapsulated DOX or ICG alone. These results indicate that the developed HIDPPNPs may serve as a feasible tool for use in anti-HER2 breast cancer therapy with reduced chemotoxicity.
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