Dual-Modal Therapeutic Nanoplatform: Harnessing Caspase-1/GSDMD Pyroptosis and Photothermal Effects for Tumor Treatment

  • ACS Appl Mater Interfaces. 2025 Dec 29. doi: 10.1021/acsami.5c14666.
Changzhen Sun  1  2 ,  Simei Yang  3 ,  Xinxin Yan  4 ,  Hongye Liao  4 ,  Tong Xia  4 ,  Xun Yang  4 ,  Xuefeng Chen  4 ,  Shuhan Yan  1 ,  Li Liu  4 ,  Jun Bai  3
Affiliations
  • 1. Drug Research Center of Integrated Traditional Chinese and Western Medicine, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, China.
  • 2. Luzhou Key Laboratory of research and development of medical institution preparations and large-scale health products, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou 646000, China.
  • 3. Environmental Health Effects and Risk Assessment Key Laboratory of Luzhou, School of Public Health, Southwest Medical University, Luzhou 646000, Sichuan, PR China.
  • 4. Department of Dermatology, The Affiliated Hospital, Southwest Medical University, Luzhou 646000, China.
PMID: 41461604 DOI: 10.1021/acsami.5c14666
Abstract

Currently, most Cancer treatment strategies focus on surgical resection of malignant tumors, complemented by physicochemical therapies such as radiotherapy and chemotherapy. However, these approaches are plagued by critical limitations, including suppression of normal cell growth and severe systemic toxicity-related side effects. In recent years, novel Cancer therapeutic modalities, particularly photothermal therapy (PTT), have arisen potentially viable alternatives to tumor therapy, because of their minimal side effects, precise controllability, and superior selectivity. This research is designed to develop an integrated antitumor, NIR-II-responsive nanoparticle, and to investigate its therapeutic potential through efficacy assessment in both cellular and animal models, along with mechanistic studies. Specifically, we engineered a hybrid nanosystem by incorporating the NIR-II Fluorescent Dye IR817 into the zeolitic imidazolate framework ZIF-8. This design strategy significantly enhances the IR817 photothermal conversion efficiency and bolsters the overall photothermal therapeutic efficacy. Notably, the dual functionality of ZIF-8 as both a nanocarrier and a Pyroptosis Inducer, combined with the photothermal effect of IR817, thereby provides improved overall antitumor outcomes.

Keywords
NIR–II–responsive nanoparticles; ZIF-8; photothermal therapy; pyroptosis; tumor treatment.