Oxygen and oxaliplatin-loaded nanoparticles combined with photo-sonodynamic inducing enhanced immunogenic cell death in syngeneic mouse models of ovarian cancer

载氧和奥沙利铂的纳米粒子与光声动力相结合,在卵巢癌同基因小鼠模型中诱导增强的免疫原性细胞死亡

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作者:Jiao Zheng, Jiangchuan Sun, Jia Chen, Shenyin Zhu, Shuning Chen, Yujiao Liu, Lan Hao, Zhigang Wang, Shufang Chang

Abstract

Immunotherapy by stimulating the host immune system has been a promising therapeutic strategy for advanced ovarian cancer. Here we describe a treatment strategy that combines chemotherapy and photo-sonodynamic therapy (PSDT) to induce systemic antitumor immunity. We have successfully fabricated phase-changeable core-shell nanoparticles (OIX_NPs), which carry oxygen in the core and the photosensitizer indocyanine green (ICG)/oxaliplatin (OXP) in the shell for our combination therapy. In the present study, we demonstrated that OIX_NPs have great potential as contrast agents to enhance photoacoustic (PA) imaging. Furthermore, our combined strategy could induce immunogenic cell death (ICD) by promoting surface exposure of calreticulin (CRT) and passive release of high-mobility group box 1 (HMGB1). Importantly, it could inhibit the growth not only primary tumors but also distant tumors in a bilateral syngeneic mouse model by increasing intratumor infiltration of cytotoxic T lymphocytes. In conclusion, the combination of chemotherapy and PSDT has the potential to enhance antitumor immunity significantly and achieve the integration of diagnosis and treatment for ovarian cancer.

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