Key Laboratory of Photochemical Conversion and Optoelectronic Materials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.
School of Future Technology, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
Nano Lett. 2024 Nov 20;24(46):14709-14719. doi: 10.1021/acs.nanolett.4c03913. Epub 2024 Nov 6.
Pyroptosis induced by photodynamic therapy (PDT) is a promising field in both PDT and immunotherapy for tumors. However, effectively inducing tumor cell pyroptosis while triggering a strong immune response using current photosensitizers remains challenging. Herein, the developed positively charged carbon dots (PCDs) nanoPSs were utilized to modulate tumor cell pyroptosis for the first time through a simple spatiotemporal programming strategy. Briefly, PCDs enabled precisely time-dependent targeting of the cell membrane or lysosome. Upon light irradiation, studies revealed that lysosome-targeted PDT primarily induced apoptosis, while membrane-targeted PDT triggered pyroptosis, resulting in enhanced PDT efficacy and robust activation of the immune response. Conclusively, studies demonstrated that PCDs could serve as a novel pyroptosis nanotuner for enhanced photodynamic-immunotherapy, thereby simultaneously eliminating primary tumors and inhibiting distant tumor growth and metastases. This spatiotemporal programming strategy unprecedentedly offers a rejuvenation of aged PSs and expands the biomedical use of CDs in immunotherapy.
光动力疗法（PDT）诱导的细胞焦亡在肿瘤的 PDT 和免疫治疗中是一个很有前途的领域。然而，使用当前的光敏剂有效地诱导肿瘤细胞焦亡并引发强烈的免疫反应仍然具有挑战性。本文中，首次开发了带正电荷的碳点（PCD）纳米 PSs，通过一种简单的时空编程策略来调节肿瘤细胞焦亡。简而言之，PCD 能够精确地、时间依赖性地靶向细胞膜或溶酶体。光照后，研究表明溶酶体靶向 PDT 主要诱导细胞凋亡，而细胞膜靶向 PDT 则触发细胞焦亡，从而提高 PDT 疗效并强烈激活免疫反应。总之，研究表明 PCD 可以作为一种新型的细胞焦亡纳米调谐器，用于增强光动力免疫治疗，从而同时消除原发性肿瘤并抑制远处肿瘤的生长和转移。这种时空编程策略前所未有地使老化的 PS 恢复活力，并扩展了 CD 在免疫治疗中的生物医学用途。
