Designing immunogenic nanotherapeutics for photothermal-triggered immunotherapy involving reprogramming immunosuppression and activating systemic antitumor responses
Designing immunogenic nanotherapeutics for photothermal-triggered immunotherapy involving reprogramming immunosuppression and activating systemic antitumor responses
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DOI：
10.1016/j.biomaterials.2020.120153
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发表时间：
2020-10-01
期刊：
影响因子：
14
通讯作者：
Zhu, Xueqiong
中科院分区：
文献类型：
--
作者：
Wang, Jing;Chang, Yanzhou;Zhu, Xueqiong
低肿瘤突变负荷和肿瘤部位内缺乏T细胞是使免疫系统瘫痪的“冷免疫肿瘤”的典型特征。通过逆转“冷肿瘤”向“热肿瘤”的转化，激活高度浸润的T细胞，从而激活抗肿瘤免疫的策略引起了人们的广泛关注。本文通过金-硒配位键制备具有免疫原性的核-壳结构Au@Se纳米粒，实现纳米粒介导的局部光热触发免疫治疗。正如预期的那样，具有改善的光热稳定性和转换效率的金纳米星（AuNS）的掺入促进了硒纳米颗粒（SeNP）的分解和转化，从而通过产生更高的热疗而导致增强的癌细胞凋亡。此外，体内实验的结果表明，SeNPs介导的化疗和AuNPs诱导的光热疗法之间的协同作用不仅产生了局部抗肿瘤免疫应答，在肿瘤相关抗原的存在下具有优异的癌症杀伤效果，而且还有效地将肿瘤相关巨噬细胞（TAMS）从M2重编程为具有杀肿瘤活性的M1表型以吞噬远处肿瘤。毫无疑问，这项研究不仅为逆转免疫抑制性肿瘤微环境提供了一种有效的策略，而且为肿瘤免疫治疗的潜在临床应用提供了新的见解。
Low tumor mutational burden and absence of T cells within the tumor sites are typical characteristics of "cold immune tumors" that paralyzes the immune system. The strategy of reversing "cold tumors" to "hot tumors" infiltrated high degree of T cells in order to activate anti-tumor immunity has attracted lots of attentions. Herein, immunogenic core-shell Au@Se NPs is fabricated by gold-selenium coordination bond to realize nanoparticles-mediated local photothermal-triggered immunotherapy. As expected, incorporation of gold nanostars (AuNSs) with improved photothermal stability and conversion efficiency promotes the disintegration and transformation of selenium nanoparticles (SeNPs), thus leading to enhanced cancer cells apoptosis by producing higher hyperthermia. Moreover, the results of in vivo experiments demonstrate that the synergy between SeNPs-mediated chemotherapy and AuNSs-induced photothermal therapy not only generated a localized antitumor-immune response with excellent cancer killing effect under the presence of tumor-associated antigens, but also effectively reprogrammed the tumor associated macrophages (TAMS) from M2 to M1 phenotype with tumoricidal activity to devour distant tumors. Without a doubt, this study not only provides a potent strategy to reverse the immunosuppressive tumor microenvironment, but also offers a new insight for potential clinical application in tumor immunotherapy.