2. Academic Validation
  3. A cisplatin prodrug-based self-assembling ozone delivery nanosystem sensitizes radiotherapy in triple-negative breast cancer

A cisplatin prodrug-based self-assembling ozone delivery nanosystem sensitizes radiotherapy in triple-negative breast cancer

  • Acta Pharm Sin B. 2025 May;15(5):2703-2722. doi: 10.1016/j.apsb.2025.03.020.
Tianyue Xu 1,  Dan Zheng 1 2,  Meixu Chen 1,  Linlin Song 1 3,  Zhihui Liu 1,  Yan Cheng 2 4,  Yujie Zhao 1,  Liwen Huang 1,  Yixuan Li 1,  Zhankun Yang 5,  Cong Li 6,  Biao Dong 7,  Jing Jing 1,  Hubing Shi 1
Affiliations

Affiliations

  • 1 Institute of Breast Health Medicine, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu 610041, China.
  • 2 Cancer Center, Breast Center, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 3 Department of Ultrasound & Laboratory of Ultrasound Medicine, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 4 Multi-omics Laboratory of Breast Diseases, State Key Laboratory of Biotherapy, National Collaborative, Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
  • 5 College of Chemical Engineering, Shijiazhuang University, Shijiazhuang 050035, China.
  • 6 Core Facilities of West China Hospital, Sichuan University, Chengdu 610041, China.
  • 7 National Clinical Research Center for Geriatrics and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China.
PMID: 40487662 DOI: 10.1016/j.apsb.2025.03.020
Abstract

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast Cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived Reactive Oxygen Species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Keywords

Cisplatin; Controlled-release system; Immunogenic cell death; Ozone; Prodrug; Radiotherapy; Reactive oxygen species; Triple-negative breast cancer.

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