VB12-Sericin-PBLG-IR780 Nanomicelles for Programming Cell Pyroptosis via Photothermal (PTT)/Photodynamic (PDT) Effect-Induced Mitochondrial DNA (mitoDNA) Oxidative Damage
VB12-Sericin-PBLG-IR780 Nanomicelles for Programming Cell Pyroptosis via Photothermal (PTT)/Photodynamic (PDT) Effect-Induced Mitochondrial DNA (mitoDNA) Oxidative Damage
复制标题
DOI：
10.1021/acsami.1c22804
复制
发表时间：
2022-04-20
影响因子：
9.5
通讯作者：
Hu, Yanfeng
中科院分区：
文献类型：
--
作者：
Guo, Weihong;Li, Zhenhao;Hu, Yanfeng
Pyroptosis是一种涉及炎症的程序性细胞死亡，可能是对抗肿瘤的有效方法，例如使用免疫疗法。然而，如何触发癌细胞的焦亡是一个重要的问题。光热（PTT）/光动力（PDT）疗法是一种非侵入性诱导癌细胞凋亡的关键策略。本工作中，用聚谷氨酸苄酯（PBLG）修饰的丝胶衍生物可以自组装，并且在水溶液中稳定。此外，将该丝胶蛋白衍生物与肿瘤靶向剂VB 12缀合并负载有IR 780。最后，我们成功地合成了VB 12-sericin-PBLG-IR 780纳米胶束。所设计的纳米胶束具有合适的粒径、球形形貌、改善的光热稳定性和高的光热转换效率（接近40%），同时产生活性氧（ROS）。通过增强细胞摄取，VB 12-sericin-PBLG-IR 780可以将更多的IR 780递送到癌细胞中。在近红外（NIR）下，VB 12-sericin-PBLG-IR 780可显著抑制ATP合酶（称为ATP 5 MC 3）的表达，随后导致线粒体损伤。线粒体活性氧簇（mitoROS）的存在导致线粒体DNA（mitoDNA）氧化损伤，进一步激活NLRP 3/Caspase-1/gasdermin D（GSDMD）依赖性细胞凋亡，并可通过细胞凋亡促进树突状细胞（DC）成熟。此外，我们的数据表明，VB 12-sericin-PBLG-IR 780可以获得出色的抗肿瘤作用，并且可以激活DC成熟，启动T细胞募集，并激发适应性抗肿瘤效率。总体而言，我们精心制备的纳米胶束可能提供一种肿瘤靶向的方法，用于程序性细胞凋亡和通过光热PTT/PDT效应诱导的线粒体DNA氧化损伤诱导抗肿瘤免疫。
Pyroptosis, a kind of programmed cell death involving inflammation, might be a powerful way to fight against tumors, for example, using immunotherapy. However, how to trigger pyroptosis in cancer cells is an important issue. Photothermal (PTT)/photodynamic (PDT) therapy is a crucial strategy for inducing cancer cell pyroptosis with noninvasiveness. In this work, a sericin derivative modified with poly(gamma-benzyl-L-glutamate) (PBLG) could self-assemble and was stable in an aqueous environment. Furthermore, the sericin derivative was conjugated with the tumor-targeting agent VB12 and loaded with IR780. Finally, we successfully synthesized VB12-sericin-PBLG-IR780 nanomicelles. The as-designed nanomicelles showed appropriate particle sizes, spherical morphology, improved photothermal stability, and high photothermal conversion efficiency (similar to 40%), which generated reactive oxygen species (ROS) simultaneously. Through enhanced cellular uptake, VB12-sericin-PBLG-IR780 could deliver more IR780 into cancer cells. With near-infrared (NIR), the VB12-sericin-PBLG-IR780 could significantly inhibit the expression of ATP synthase, called ATP5MC3, followed by mitochondrial damage. The presence of mitochondrial reactive oxygen species (mitoROS) led to oxidative damage of mitochondrial DNA (mitoDNA), which further activates NLRP3/Caspase-1/gasdermin D (GSDMD)-dependent pyroptosis and could promote dendritic cell (DC) maturation by pyroptosis. Furthermore, our data showed that VB12-sericin-PBLG-IR780 could achieve a brilliant antitumor effect and could activate DC maturation, initiate T-cell recruiting, and prime adaptive antitumor efficiency. Overall, our well-prepared nanomicelles might offer a tumor-targeted approach for programmed cell pyroptosis and inducing antitumor immunity via photothermal PTT/PDT effect-induced mitoDNA oxidative damage.