2. Academic Validation
  3. Carrier-Free Nanoplatform via Evoking Pyroptosis and Immune Response against Breast Cancer

Carrier-Free Nanoplatform via Evoking Pyroptosis and Immune Response against Breast Cancer

  • ACS Appl Mater Interfaces. 2022 Dec 20. doi: 10.1021/acsami.2c17579.
Lei Li 1,  Hailong Tian 2,  Zhe Zhang 2,  Ning Ding 1,  Kai He 1,  Shuaijun Lu 3,  Ruolan Liu 1,  Peijie Wu 1,  Yu Wang 2,  Bo He 2,  Maochao Luo 2,  Peilan Peng 2,  Mao Yang 4,  Edouard C Nice 5,  Canhua Huang 1 2,  Na Xie 2,  Dong Wang 1,  Wei Gao 6
Affiliations

Affiliations

  • 1 School of Basic Medical Sciences and State Key Laboratory of Southwestern Chinese Medicine Resources, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
  • 2 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital and West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
  • 3 The Affiliated Hospital of Ningbo University School of Medicine, Ningbo 315020, China.
  • 4 Institute for Cancer Medicine and School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan 646000, China.
  • 5 Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
  • 6 Clinical Genetics Laboratory, Affiliated Hospital & Clinical Medical College of Chengdu University, Chengdu 610081, China.
PMID: 36538368 DOI: 10.1021/acsami.2c17579
Abstract

Pyroptosis, as a novel mode of cell death, has been proven to have impressive antitumor effects. Dying cells undergoing Pyroptosis can elicit antitumor immunity by the release of tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs). Accordingly, developing an effective, stable, and controllable nanoplatform that can promote these two side effects is a promising option for Cancer therapy. In this study, we designed a carrier-free chemo-photodynamic nanoplatform (A-C/NPs) using a co-assembly strategy with cytarabine (Ara-C) and chlorin e6 (Ce6) to induce Pyroptosis and a subsequent immune response against breast Cancer. Mechanistically, A-C/NPs can trigger GSDME-mediated Pyroptosis in a controllable manner through Reactive Oxygen Species (ROS) accumulation, causing immunogenic cell death (ICD), in which dying cells release high-mobility group box 1 (HMGB1), adenosine triphosphate (ATP), and Calcitonin (CRT). Additionally, Ara-C can stimulate the maturation of cytotoxic T lymphocytes to act synergistically with Ce6-mediated immunogenic cell death (ICD), collectively augmenting the Anticancer effect of A-C/NPs. The A-C/NPs showed excellent suppressive effects on the growth of orthotopic, abscopal, and recurrent tumors in a breast Cancer mouse model. The chemo-photodynamic therapy (PDT) using the proposed nanomedicine strategy could be a novel strategy for triggering Pyroptosis and improving the global Anticancer immune response.

Keywords

breast cancer; carrier-free; chemo-photodynamic therapy; immunotherapy; pyroptosis.

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