(282e) Development of Anti-HER2 Indocyanine Green-Doxorubicin-Encapsulated Peg-b-PLGA Copolymeric Nanoparticles for Target Photochemotherapy of Breast Cancer Cells in Vitro

INTRODUCTION: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females worldwide. Among various types of breast cancer, the one with overexpression of anti-human epidermal growth factor receptor 2 (HER2) is strongly correlated with tumorigenesis, oncogenic transformation, and metastasis of breast cancer. Moreover, the HER2-positive breast cancer is known to be more aggressive and resistant to medicinal treatment, indicating that improving the tumor eradication approach instead of trying anti-cancer drugs persistently is truly needed for curing HER2-positive breast cancer. In this study, we aimed to develop an anti-HER2 indocyanine green (ICG)-doxorubicin (DOX)-loaded polyethylene glycol-poly(lactic-co-glycolic acid) diblock copolymeric nanoparticles (HIDPPNPs) for target photochemotherapy of HER2-positive breast cancer cells in vitro.

RESULTS: The HIDPPNPs are fabricated using a solvent evaporation technique followed by carbodiimide-mediated antibody conjugation on the nanoparticle surface. The mean size and surface charge of the HIDPPNP are 266 ± 4.26 nm with a polydispersity index of 0.07 – 0.12 and -12 ± 4.48 mV, respectively. Compared with freely dissolved ICG, the HIDPPNPs with enhanced thermal stability to the entrapped ICG are able to generate a hyperthermia effect at concentrations ≥1 μM ICG equivalent and may provide increased production of singlet oxygen under near infrared (NIR; 808-nm) laser exposure with an intensity of 6 W/cm². Furthermore, the uptake efficiency of the HIDPPNPs in MDA-MB-453/HER2(+) cells is approximately 2-fold higher than that in MCF7/HER2(−) cells, demonstrating the targetability of the HIDPPNPs to HER2-expressing cells. Based on the viability analysis, the HIDPPNPs exhibit effective cytotoxicity upon NIR exposure (808 nm; 6 W/cm²), and the resulting cell death rate is even higher than that caused by using twice amount of encapsulated DOX or ICG alone. These results show that the HIDPPNPs are certainly effective on HER2(+)-cancer cell killing upon NIR exposure. We reason that the enhanced anticancer effectiveness is contributed from 1) HER2 target specificity of the HIDPPNPs that enabled an efficient cell internalization and 2) robust photo (photothermal & photodynamic)-chemo-tumoricidal capacity.

CONCLUSION: In this study, we have successfully developed HIDPPNPs for targeted photochemotherapy of HER2-positive breast cancer cells in vitro. We anticipate that the HIDPPNP may serve as a feasible anticancer tool with reduced chemotoxicity in the clinic and further investigations are currently in progress.