posted on 2022-12-20, 17:09authored byLei 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
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.