State Key Laboratory of Structural Chemistry, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou, 350002, China.
Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, 361021, China.
Adv Sci (Weinh). 2024 Oct;11(39):e2406340. doi: 10.1002/advs.202406340. Epub 2024 Aug 19.
Pyroptosis possesses potent antitumor immune activity, making pyroptosis inducer development a promising direction for tumor immunotherapy. Persistent luminescence nanoparticles (PLNPs) are highly sensitive optical probes extensively employed in tumor diagnosis and therapy. However, a pyroptosis inducer based on PLNPs has not been reported yet. Herein, polyethylene glycol-poly lactic acid-co-glycolic acid (PEG-PLGA: PP) modified biodegradable CaS:Eu (CSE@PP) PLNPs are synthesized as a pyroptosis inducer for tumor immunotherapy for the first time. The synthesized CSE@PP possesses biowindow persistent luminescence (PersL) and pH-responsive degradation properties, allowing it to remain stable under neutral pH but degrade when exposed to weak acid (pH < 6.5). During degradation within the tumor, CSE@PP constantly releases HS and Ca while its PersL gradually fades away. Thus, the PersL signal can self-monitor HS and Ca release. Furthermore, the released HS and Ca result in mitochondrial dysfunction and the inactivation of reactive oxygen species scavenging enzymes, synergistic facilitating intracellular oxidative stress, which induces caspase-1/GSDM-D dependent pyroptosis and subsequent antitumor immune responses. In a word, it is confirmed that CSE@PP can self-monitor HS and Ca release and pyroptosis-mediated tumor Immunotherapy. This work will facilitate biomedical applications of PLNPs and inspire pyroptosis-induced tumor immunotherapy.
细胞焦亡具有强大的抗肿瘤免疫活性，因此开发细胞焦亡诱导剂是肿瘤免疫治疗的一个有前景的方向。持续发光纳米粒子（PLNPs）是一种高度灵敏的光学探针，广泛应用于肿瘤的诊断和治疗。然而，基于 PLNPs 的细胞焦亡诱导剂尚未见报道。在此，我们首次合成了聚乙二醇-聚乳酸-co-羟基乙酸（PEG-PLGA：PP）修饰的可生物降解的 CaS:Eu（CSE@PP）PLNPs 作为肿瘤免疫治疗的细胞焦亡诱导剂。合成的 CSE@PP 具有生物窗口持续发光（PersL）和 pH 响应性降解特性，使其在中性 pH 下保持稳定，但在弱酸性（pH < 6.5）下会降解。在肿瘤内降解过程中，CSE@PP 不断释放 HS 和 Ca，同时其 PersL 逐渐消失。因此，PersL 信号可以自我监测 HS 和 Ca 的释放。此外，释放的 HS 和 Ca 导致线粒体功能障碍和活性氧清除酶失活，协同促进细胞内氧化应激，诱导 caspase-1/GSDM-D 依赖性细胞焦亡和随后的抗肿瘤免疫反应。总之，证实了 CSE@PP 可以自我监测 HS 和 Ca 的释放以及细胞焦亡介导的肿瘤免疫治疗。这项工作将促进 PLNPs 在生物医学中的应用，并激发细胞焦亡诱导的肿瘤免疫治疗。
