Molecules, Vol. 29, Pages 1845: Self-Assembled Matrine-PROTAC Encapsulating Zinc(II) Phthalocyanine with GSH-Depletion-Enhanced ROS Generation for Cancer Therapy

Molecules, Vol. 29, Pages 1845: Self-Assembled Matrine-PROTAC Encapsulating Zinc(II) Phthalocyanine with GSH-Depletion-Enhanced ROS Generation for Cancer Therapy Molecules doi: 10.3390/molecules29081845 Authors: Sitong Lai Bing Wang Kunhui Sun Fan Li Qian Liu Xie-An Yu Lihe Jiang Lisheng Wang The integration of a multidimensional treatment dominated by active ingredients of traditional Chinese medicine (TCM), including enhanced chemotherapy and synergistically amplification of oxidative damage, into a nanoplatform would be of great significance for furthering accurate and effective cancer treatment with the active ingredients of TCM. Herein, in this study, we designed and synthesized four matrine-proteolysis-targeting chimeras (PROTACs) (depending on different lengths of the chains named LST-1, LST-2, LST-3, and LST-4) based on PROTAC technology to overcome the limitations of matrine. LST-4, with better anti-tumor activity than matrine, still degrades p-Erk and p-Akt proteins. Moreover, LST-4 NPs formed via LST-4 self-assembly with stronger anti-tumor activity and glutathione (GSH) depletion ability could be enriched in lysosomes through their outstanding enhanced permeability and retention (EPR) effect. Then, we synthesized LST-4@ZnPc NPs with a low-pH-triggered drug release property that could release zinc(II) phthalocyanine (ZnPc) in tumor sites. LST-4@ZnPc NPs combine the application of chemotherapy and phototherapy, including both enhanced chemother...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research