Photodynamic therapy produces enhanced efficacy of antitumor immunotherapy by simultaneously inducing intratumoral release of sorafenib
Photodynamic therapy produces enhanced efficacy of antitumor immunotherapy by simultaneously inducing intratumoral release of sorafenib
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光动力疗法通过同时诱导索拉非尼瘤内释放来增强抗肿瘤免疫疗法的疗效
DOI：
10.1016/j.biomaterials.2020.119845
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发表时间：
2020-05-01
期刊：
影响因子：
14
通讯作者：
Sun, Tianmeng
中科院分区：
文献类型：
--
作者：
Sun, Xu;Cao, Ziyang;Sun, Tianmeng
光动力疗法(PDT)能破坏局部肿瘤细胞，诱导有效的抗肿瘤免疫反应，已被应用于浅表实体瘤患者的治疗。然而，PDT的许多全身副作用，如疼痛和皮肤光敏，限制了这种治疗选择。此外，免疫抑制的肿瘤微环境被发现是PDT诱导抗肿瘤免疫的另一个关键屏障。因此，有效增强低剂量PDT对肿瘤细胞的细胞毒作用，抑制肿瘤免疫抑制的肿瘤微环境可能是克服PDT这些缺点的可行策略。在这里，索拉非尼和氯素e6共负载的活性氧(ROS)响应性纳米颗粒(NP-SFB/CE6)被开发出来，通过在PDT时在肿瘤内释放索拉非尼来改善抗肿瘤反应。在660 nm激光照射下，三氯乙烯(Ce6)产生的ROS破坏了纳米粒，促进了索拉非尼的级联释放。快速释放的索拉非尼与低剂量的PDT协同作用，通过诱导强大的T细胞依赖的局部和全身抗肿瘤免疫反应，重塑肿瘤免疫微环境，限制细胞毒性CD8(+)T细胞和免疫抑制细胞之间的相互作用，从而抑制肿瘤生长。本研究为光动力疗法的级联放大抗肿瘤作用提供了新的途径。
Photodynamic therapy (PDT) can destroy local tumor cells and induce effective antitumor immune responses, and has been applied in the treatment of patients with superficial solid tumors. Numerous systemic side effects of PDT, such as pain and skin photosensitivity, however, limit this therapeutic option. In addition, the immunosuppressive tumor microenvironment has been found to be another critical barrier for the antitumor immunity induced by PDT. Therefore, effectively enhancing the cytotoxicity to tumor cells of low-dose PDT and inhibiting the tumor immunosuppressive tumor microenvironment may be a feasible strategy to overcome these drawbacks of PDT. Here, a sorafenib and chlorin e6 co-loaded reactive oxygen species (ROS)-responsive nanoparticle (NP-sfb/ce6) is developed to improve antitumor responses by intratumoral release of sorafenib at the time of PDT. Under 660-nm laser irradiation, ROS produced by chlorin e6 (ce6) destruct the nanoparticles, resulting in boosted sorafenib cascade release. The rapidly released sorafenib acts synergistically with the low-dose PDT to inhibit tumor growth by inducing strong T cell-dependent local and systemic antitumor immune responses, reprograming the tumor immune microenvironment, and limiting the interaction between cytotoxic CD8(+) T cells and immunosuppressive cells. This study provides new avenues for cascade-amplifying antitumor effects of photodynamic therapy.