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

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.
Authors	Lei Li, Hailong Tian, Zhe Zhang, Ning Ding, Kai He, Shuaijun Lu, Ruolan Liu, Peijie Wu, Yu Wang, Bo He, Maochao Luo, Peilan Peng, Mao Yang, Edouard C Nice, Canhua Huang, Na Xie, Dong Wang, Wei Gao
Journal	ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 15 Issue 1 Pg. 452-468 (Jan 11 2023) ISSN: 1944-8252 [Electronic] United States
PMID	36538368 (Publication Type: Journal Article)
Chemical References	Photosensitizing Agents Cytarabine
Topics	Animals Mice Photosensitizing Agents (pharmacology) Photochemotherapy Pyroptosis Nanoparticles Neoplasms Cytarabine Immunity Cell Line, Tumor

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