Abstract P6-10-02: Self-assembled nano drugs of pyrotinib and indocyanine green based on photothermal photodynamic therapy

Abstract Background: Photothermal and photodynamic therapy is a new tumor treatment strategy, which can kill tumor cells and reduce the damage to surrounding normal tissues, but the lack of targeting limits its efficacy. In this study, the targeted photothermal and photodynamic nanodrug P/ICG was synthesized by self-assembly of the targeted drug pyrotinib and photosensitizer indocyanine green (ICG), and its application in the photothermal and photodynamic therapy of HER2 positive breast cancer was explored. Method: In this study, the nano drug P/ICG was self-assembly synthesized of pyrotinib and ICG, and its physical parameters and stability were tested. We used 808nm near-infrared light and infrared thermal imager to verify the photothermal effect of nano drugs. Then we used DCFH-DA probe to detect the level of ROS in cells by laser confocal and flow cytometry to verify the photodynamic effect of the nano drug, and verified the antitumor effect of P/ICG combined with near-infrared light irradiation in vitro. We established a PDX mouse breast cancer model and verified the efficacy and safety of P/ICG in the treatment of HER2-positive breast cancer in vitro. Finally, the effect of P/ICG on ferroptosis was verified by MDA, CCK8 and WB experiments. Result: We mixed pyrotinib and ICG in a certain proportion, and purified them by high-speed centrifugation and ultrafiltration to synthesize nano drug P/ICG. P/ICG has good stability and can be effectively ingested by HER2-positive breast cancer cells. Subsequently, we proved through in vitro and in vivo experiments that P/ICG combined with near-infrared light irradiation can significantly inhibit the growth of tumor cells and improve the survival rate of mice. At the same time, P/ICG combined with near-infrared light irradiation increased the phosphorylation of Nrf2 protein, increased the level of free KEAP1 protein, and decreased the levels of SLC7A11, GPX4 and FTH1 protein, significantly increased the lipid peroxidation of tumor cells, and promoted the ferroptosis of tumor cells. Conclusion: Pyrotinib and ICG self-assembled nano drug P/ICG can significantly promote the ferroptosis of HER2-positive breast cancer cells and inhibit the growth of cancer cells, which can be used as a new strategy for the treatment of HER2-positive breast cancer. Key words: pyrotinib; HER2-positive breast cancer; Photothermal therapy; photodynamic therapy Citation Format: Juncheng Xuhong, Jun Deng, Jun Jiang, Xiaowei Qi. Self-assembled nano drugs of pyrotinib and indocyanine green based on photothermal photodynamic therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-10-02.