Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China; Institute of Ultrasound Imaging, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
J Control Release. 2021 Apr 10;332:448-459. doi: 10.1016/j.jconrel.2021.02.032. Epub 2021 Mar 2.
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.
免疫疗法通过刺激宿主免疫系统已成为治疗晚期卵巢癌的一种有前途的治疗策略。在这里，我们描述了一种将化疗和光动力疗法（PSDT）相结合以诱导全身抗肿瘤免疫的治疗策略。我们成功地制备了相变型核壳纳米粒子（OIX_NPs），其核中携带氧气，壳中携带光敏剂吲哚菁绿（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 具有作为增强光声（PA）成像的造影剂的巨大潜力。此外，我们的联合策略可以通过促进钙网蛋白（CRT）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，它不仅可以通过增加肿瘤内细胞毒性 T 淋巴细胞浸润来抑制原发性肿瘤的生长，还可以在双侧同种小鼠模型中抑制远处肿瘤的生长。总之，化疗和 PSDT 的联合应用有可能显著增强抗肿瘤免疫，并实现卵巢癌的诊断和治疗一体化。
