| Autor: |
Xie L; Precision Research Center for Refractory Diseases in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.; Department of Pharmacology, the Eighth Affiliated Hospital, Sun Yat-sen University, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Shenzhen 510275, China., Wang L; Precision Research Center for Refractory Diseases in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China., Li L; Department of Pharmacology, the Eighth Affiliated Hospital, Sun Yat-sen University, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Shenzhen 510275, China., Liu C; Department of Pharmacology, the Eighth Affiliated Hospital, Sun Yat-sen University, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Shenzhen 510275, China., Guo L; Precision Research Center for Refractory Diseases in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.; School of Advanced Materials and Nanotechnology, Interdisciplinary Research Center of Smart Sensors, Xidian University, Xi'an 710126, China., Liao Y; Department of Pharmacology, the Eighth Affiliated Hospital, Sun Yat-sen University, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Shenzhen 510275, China., Zhou S; Precision Research Center for Refractory Diseases in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China., Wu W; School of Advanced Materials and Nanotechnology, Interdisciplinary Research Center of Smart Sensors, Xidian University, Xi'an 710126, China., Duo Y; Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02138, United States., Shi L; Precision Research Center for Refractory Diseases in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China., Yuan M; Precision Research Center for Refractory Diseases in Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.; Department of Pharmacology, the Eighth Affiliated Hospital, Sun Yat-sen University, Joint Laboratory of Guangdong-Hong Kong-Macao Universities for Nutritional Metabolism and Precise Prevention and Control of Major Chronic Diseases, Shenzhen 510275, China. |
| Abstrakt: |
Photosensitizers have been widely used to cause intratumoral generation of reactive oxygen species (ROS) for cancer therapy, but they are easily disturbed by the autophagy pathway, a self-protective mechanism by mitigating oxidative damage. Hereby, we reported a simple and effective strategy to construct a carrier-free nanodrug, Ce6@CQ namely, based on the self-assembly of the photosensitizer chlorin e6 (Ce6) and the autophagy inhibitor chloroquine (CQ). Specifically, Ce6@CQ avoided the unexpected toxicity caused by the regular nanocarrier and also ameliorated its stability in different conditions. Light-activated Ce6 generated cytotoxic ROS and elicited part of the immunogenic cell death (ICD). Moreover, CQ induced autophagy dysfunction, which hindered self-healing in tumor cells and enhanced photodynamic therapy (PDT) to exert a more potent killing effect and more efficient ICD. Also, Ce6@CQ could effectively accumulate in the xenograft breast tumor site in a mouse model through the enhanced permeability and retention (EPR) effect, and the growth of breast tumors was effectively inhibited by Ce6@CQ with light. Such a carrier-free nanodrug provided a new strategy to improve the efficacy of PDT via the suppression of autophagy to digest ROS-induced toxic substances. |
