Engineering antigen as photosensitiser nanocarrier to facilitate ROS triggered immune cascade for photodynamic immunotherapy
Engineering antigen as photosensitiser nanocarrier to facilitate ROS triggered immune cascade for photodynamic immunotherapy
复制标题
将抗原工程化为光敏纳米载体，促进 ROS 触发免疫级联，用于光动力免疫治疗
DOI：
10.1016/j.biomaterials.2020.119964
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发表时间：
2020
期刊：
影响因子：
14
通讯作者：
Li Yongyong
中科院分区：
文献类型：
--
作者：
Wang Huaiji;Wang Kun;He Lianghua;Liu Ying;Dong Haiqing;Li Yongyong
尽管光动力疗法(PDT)存在免疫原性细胞死亡(ICD)和抗原交叉提呈(AC)，但总体免疫效果相当有限。本研究旨在通过空间包裹抗原作为光敏纳米载体来扩大PDT的免疫潜力，从而触发有效的免疫级联用于光动力免疫治疗。通过驱动OVA分子间的分子间二硫键网络，实现了OVA的亚100 nm纳米组装。随后将负载光敏剂Ce6(ON)的OVA纳米颗粒包裹在B16-OVA癌细胞膜上，得到覆盖在(MON)上的膜。重要的是，激光照射产生的ROS显著增强了OVA抗原的交叉递呈效率。同时，由于癌细胞膜的包裹，MON被赋予了对肿瘤的亲和性靶向。在治疗B16-OVA荷瘤小鼠中，MON有效地触发了免疫级联反应，在激光照射下完全消除了肿瘤，并激发了长期的抗肿瘤免疫记忆效应。相反，如果在纳米颗粒设计中用OVA代替牛血清蛋白(BSA)，或者用MON治疗非OVA表达的肿瘤，则发现边际效应。抗原纳米载体的设计有望通过增强免疫级联来补充传统的光动力疗法，从而导致独特的光动力免疫疗法。
Despite of the documented immunogenic cell death (ICD) and antigen cross-presentation (AC) in photodynamic therapy (PDT), the overall immune efficacy is rather limited. This study aims to expand the immune potential of PDT by spatially packaging antigen as photosensitiser nanocarrier to trigger efficient immune cascade for photodynamic immunotherapy. The package of ovalbumin antigen (OVA) into sub-100 nm nano-assembly is realized by driving intermolecular disulfide network between OVA molecules. OVA nanoparticles loading photosensitiser Ce6 (ON) are subsequently coated with B16-OVA cancer cell membrane, resulting in membrane cloaked ON (MON). Importantly, laser irradiation generated ROS significantly potentiates OVA antigen cross-presentation efficiency. Whilst, MON is endowed with homophilic targeting towards tumor due to cancer cell membrane coating. In treating B16-OVA tumor-bearing mice, MON effectively triggers the immune cascade, completely eliminates the tumor under laser irradiation and provokes a long-term antitumor immune memory effect. Conversely, a marginal effect is found if substituting OVA for bovine serum protein (BSA) in nanoparticle design or using MON to treat non-OVA expressing tumor. The antigen nanocarrier design promises to complement conventional PDT by boosting immune cascade, thereby leading to unique photodynamic immunotherapy.