Safe transportation and targeted destruction: Albumin encapsulated aggregation‐induced emission photosensitizer nanoaggregate for tumor photodynamic therapy through mitochondria damage‐triggered pyroptosis
Juanmei Cao,
Yong Qu,
Shaojie Zhu,
Jinshan Zhan,
Yiting Xu,
Yifan Jin,
Yuqing Wang,
Zhuoxia Li,
Chuxing Chai,
Xiangwei Wu,
Meng Gao,
Changzheng Huang,
Min Li
Affiliations
Juanmei Cao
Department of Dermatology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Yong Qu
Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Shaojie Zhu
National Engineering Research Center for Tissue Restoration and Reconstruction, Key Laboratory of Biomedical Engineering of Guangdong Province, Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, Innovation Center for Tissue Restoration and Reconstruction, School of Materials Science and Engineering South China University of Technology Guangzhou China
Jinshan Zhan
Department of Dermatology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Yiting Xu
Central Laboratory, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Yifan Jin
Department of Dermatology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Yuqing Wang
Department of Dermatology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Zhuoxia Li
Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Chuxing Chai
Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Xiangwei Wu
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Department of Hepatobiliary Surgery The First Affiliated Hospital of Shihezi University Shihezi University School of Medicine Shihezi China
Meng Gao
National Engineering Research Center for Tissue Restoration and Reconstruction, Key Laboratory of Biomedical Engineering of Guangdong Province, Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, Innovation Center for Tissue Restoration and Reconstruction, School of Materials Science and Engineering South China University of Technology Guangzhou China
Changzheng Huang
Department of Dermatology, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Min Li
Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College Huazhong University of Science and Technology Wuhan China
Abstract Photodynamic therapy is a highly recommended alternative treatment for solid tumors, such as cutaneous or luminal tumors, in clinical practice. However, conventional photosensitizers (PSs) often induce undesirable phototoxic effects because of their normal tissue distribution and a reduction in antitumor effects resulting from aggregation‐caused quenching effects. The present study developed a novel nano‐formulated aggregation‐induced emission (AIE)‐characteristic PS, nab‐TTVPHE, which is composed of human serum albumin as a carrier and TTVPHE as a therapeutic agent, as a more effective cancer treatment with lower phototoxic effects. Notably, the reactive oxygen species generated by TTVPHE were shielded by the nanoaggregate structure, and the photodynamic activity was after nanostructure dissociation. Nab‐TTVPHE was actively internalized in tumor cells via secreted protein, acidic and rich in cysteine and released to form nanoaggregates. TTVPHE accumulated in mitochondria, where it triggered mitochondrial damage under light irradiation via its photodynamic activity and induced pyroptosis via the caspase‐3/gasdermin E (GSDME) signaling pathway to kill tumor cells. Therefore, this nano‐formulated AIE‐characteristic PS provides an innovative strategy for cancer treatment with lower phototoxic effect and the ability to boost potential antitumor immunity via GSDME‐mediated pyroptosis.
