An Aged Tree with a New Bloom: A Simple Spatiotemporal Programming Strategy Enables Carbon Dot Photosensitizers to Regulate Cell Pyroptosis for Enhanced Tumor Photodynamic-Immunotherapy

• Published in: Nano letters 2024-11, Vol.24 (46), p.14709-14719
• Main Authors: Chen, Tiejin, Liang, Ke, Wang, Jian, Li, Jian, Xue, Xiaokuang, Hao, Yongliang, Liang, Huanyi, Ren, Haohui, Xiao, Haihua, Ge, Jiechao, Tang, Bo
• Format: Article
• Language: English
• ISSN: 1530-6984; 1530-6992; 1530-6992
• DOI: 10.1021/acs.nanolett.4c03913

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, in vitro 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, in vivo 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.