Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences , Shandong University , 44 Wenhuaxi Road , Jinan , Shandong Province 250012 , China.
Key Laboratory of Colloid & Interface Chemistry (Ministry of Education) , Shandong University , Jinan , Shandong Province 250100 , China.
ACS Appl Mater Interfaces. 2019 Nov 20;11(46):42904-42916. doi: 10.1021/acsami.9b13556. Epub 2019 Nov 8.
Potentiating systemic immunity against breast cancer is in the most urgent demand as breast cancer is less sensitive to immune checkpoint blockade. Although phototherapy and some chemotherapy can trigger immunogenic cell death (ICD) for T cell-mediated antitumor immune response, their immunotherapy efficacy is severely restricted by insufficient phototherapeutic capability and severe multidrug resistance (MDR). Inspired by both the hypersensitivity to phototherapy and the key role of MDR for mitochondria, a rationally engineered immunity amplifier via mitochondria-targeted photochemotherapeutic nanoparticles was, for the first time, achieved to fight against low-immunogenic breast cancer without additional immune agents. The newly synthesized task-specific mitochondria-targeted IR780 derivative (T780) was integrated with chemotherapeutic doxorubicin (DOX) to form multifunctional nanoparticles via an assembling strategy along with bovine serum albumin (BSA) as a biomimetic corona (BSA@T780/DOX NPs). The in situ enhancement in both phototherapy and MDR reversal by targeting mitochondria with BSA@T780/DOX NPs boosted highly efficient ICD toward excellent antitumor immune response. The newly developed strategy not only eradicated the primary tumor but also eliminated the bilateral tumors efficiently, as well as preventing metastasis and postsurgical recurrence, demonstrating great interest for fighting against low-immunogenic breast cancer.
增强全身对乳腺癌的免疫力是当务之急，因为乳腺癌对免疫检查点阻断的敏感性较低。虽然光疗和一些化疗可以引发免疫原性细胞死亡（ICD），从而促进 T 细胞介导的抗肿瘤免疫反应，但它们的免疫治疗效果受到光疗能力不足和严重多药耐药（MDR）的严重限制。受光疗的高敏感性和线粒体对 MDR 的关键作用的启发，首次通过靶向线粒体的光化疗纳米粒子实现了一种合理设计的免疫增强剂，用于对抗低免疫原性乳腺癌，而无需额外的免疫制剂。新合成的靶向线粒体的特定任务 IR780 衍生物（T780）与化疗药物阿霉素（DOX）通过组装策略结合牛血清白蛋白（BSA）形成多功能纳米颗粒（BSA@T780/DOX NPs）。通过 BSA@T780/DOX NPs 靶向线粒体来原位增强光疗和 MDR 逆转，促进了高效 ICD，从而产生了优异的抗肿瘤免疫反应。新开发的策略不仅根除了原发性肿瘤，还有效地消除了双侧肿瘤，同时防止了转移和术后复发，为对抗低免疫原性乳腺癌提供了极大的兴趣。
