Oxygen and oxaliplatin-loaded nanoparticles combined with photo-sonodynamic inducing enhanced immunogenic cell death in syngeneic mouse models of ovarian cancer
Oxygen and oxaliplatin-loaded nanoparticles combined with photo-sonodynamic inducing enhanced immunogenic cell death in syngeneic mouse models of ovarian cancer
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DOI：
10.1016/j.jconrel.2021.02.032
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发表时间：
2021-03-14
影响因子：
10.8
通讯作者：
Chang, Shufang
中科院分区：
文献类型：
--
作者：
Zheng, Jiao;Sun, Jiangchuan;Chang, Shufang
通过刺激宿主免疫系统进行免疫治疗是治疗晚期卵巢癌的一种很有前途的治疗策略。在这里，我们描述了一种结合化疗和光声动力疗法(PSDT)来诱导全身抗肿瘤免疫的治疗策略。我们已经成功地制备了可相变的核壳纳米粒子(OIX_NPs)，它在核心携带氧气，在外壳中携带光敏剂吲哚青绿(ICG)/奥沙利铂(OXP)，用于我们的联合治疗。在本研究中，我们证明了OIX_NPs作为造影剂在增强光声成像方面具有很大的潜力。此外，我们的联合策略可以通过促进钙网蛋白(CRT)的表面暴露和高迁移率族蛋白1(HMGB1)的被动释放来诱导免疫原性细胞死亡(ICD)。重要的是，在双侧同基因小鼠模型中，它不仅可以抑制原发肿瘤的生长，还可以通过增加肿瘤内细胞毒性T淋巴细胞的渗透来抑制远处肿瘤的生长。综上所述，化疗联合PSDT有可能显著增强卵巢癌的抗肿瘤免疫能力，实现卵巢癌的诊疗一体化。
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.