VB12-Sericin-PBLG-IR780 Nanomicelles for Programming Cell Pyroptosis via Photothermal (PTT)/Photodynamic (PDT) Effect-Induced Mitochondrial DNA (mitoDNA) Oxidative Damage

作者：Weihong Guo, Zhenhao Li, Huilin Huang, Zhijun Xu, Zhian Chen, Guodong Shen, Zhenyuan Li, Yingxin Ren, Guoxin Li, Yanfeng Hu · 发表于：ACS Applied Materials & Interfaces · 年份：2022 · DOI：10.1021/acsami.1c22804 · 被引用次数：73 · 研究领域：Inflammasome and immune disorders、Toxoplasma gondii Research Studies、Nanoplatforms for cancer theranostics

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(γ-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 (∼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-IR7...