Synergistic Local Combination of Radiation and Anti-Programmed Death Ligand 1 Immunotherapy Using Radiation-Responsive Splintery Metallic Nanocarriers
Synergistic Local Combination of Radiation and Anti-Programmed Death Ligand 1 Immunotherapy Using Radiation-Responsive Splintery Metallic Nanocarriers
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DOI：
10.1021/acsnano.0c04701
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发表时间：
2020-10-27
期刊：
影响因子：
17.1
通讯作者：
Kim, Dong-Hyun
中科院分区：
文献类型：
--
作者：
Choi, Bongseo;Choi, Hyunjun;Kim, Dong-Hyun
放射治疗(RT)介导的肿瘤免疫原性为RT和免疫治疗的协同结合提供了机会。临床上的挑战之一是获得最佳的联合放射治疗和免疫治疗的疗效，同时将重叠毒性降至最低。为了实现联合RT和抗程序性死亡配体1(Ad-L1)免疫治疗的协同治疗效果，采用分级双金属超纳米结构的方法合成了RT反应的裂片状雪花状Au纳米载体(SAuNC)。连接L和银纳米晶的原生Au纳米晶LIN S-AUNC表现出RT响应的结构形变，导致在S-AUNC中的载物Ad-Li在RT触发下释放。局部联合RT和apd-L1负载的S-AuNC可显著增强肿瘤微环境转化所需的免疫原性细胞死亡。RT触发的局部APDL1释放允许受控的时空组合RT和APDL1免疫治疗，导致协同抗癌适应性免疫反应，并将全身免疫相关的不良反应降至最低。
Radiation therapy (RT)-mediated tumor immunogenicity offers an opportunity for synergistic combination RT and immunotherapy. One of the challenges in the clinic is to attain the optimum efficacy of combination RT and immunotherapy with minimized overlapping toxicities. Here, to achieve synergistic therapeutic efficacy of combinational RT and anti-programmed death ligand 1 (aPD-L1) immunotherapy, RT-responsive splintery snowflake-like Au nanocarriers (SAuNC) were synthesized with a method for hierarchical bimetallic supra-nanostructures. Primary Au nanocrystals interconnected l with Ag nanocrystals lin S-AuNC showed RT-responsive structural deformation resulting in RT-triggered release of cargo aPD-LI in S-AuNC. The local combination of RT and aPD-L1 loaded S-AuNC significantly enhanced the immunogenic cell death for tumor microenvironment conversion. RT-triggered local aPD-L1 release allowed a controlled spatiotemporal combination RT and aPD-L1 immunotherapy resulting in a synergistic anticancer adaptive immune response with minimized systemic immune-related adverse effects.