TY - JOUR
T1 - Cancer-Cell-Activated Photodynamic Therapy Assisted by Cu(II)-Based Metal-Organic Framework
AU - Wang, Yuanbo
AU - Wu, Wenbo
AU - Liu, Jingjing
AU - Manghnani, Purnima Naresh
AU - Hu, Fang
AU - Ma, Dou
AU - Teh, Cathleen
AU - Wang, Bo
AU - Liu, Bin
N1 - Publisher Copyright:
Copyright © 2019 American Chemical Society.
PY - 2019
Y1 - 2019
N2 - Activation of photosensitizers (PSs) in targeted lesion and minimization of reactive oxygen species (ROS) depletion by endogenous antioxidants constitute promising approaches to perform highly effective image-guided photodynamic therapy (PDT) with minimal non-specific phototoxicity. Traditional strategies to fabricate controllable PS platforms rely on molecular design, which requires specific modification of each PS before PDT. Therefore, construction of a general tumor-responsive PDT platform with minimum ROS loss from endogenous antioxidant, typically glutathione (GSH), is highly desirable. Herein, MOF-199, a Cu(II) carboxylate-based metal-organic framework (MOF), is selected to serve as an inert carrier to load PSs with prohibited photosensitization during delivery. After cellular uptake, Cu (II) in the MOFs effectively scavenges endogenous GSH, concomitantly induces decomposition of MOF-199 to release the encapsulated PSs, and recovers their ROS generation. In vitro and in vivo experiments demonstrate highly effective cancer cell ablation and anticancer PDT with diminished normal cell phototoxicity. This strategy is generally applicable to PSs with both aggregation-induced emission and aggregation-caused quenching to implement activatable and enhanced image-guided PDT.
AB - Activation of photosensitizers (PSs) in targeted lesion and minimization of reactive oxygen species (ROS) depletion by endogenous antioxidants constitute promising approaches to perform highly effective image-guided photodynamic therapy (PDT) with minimal non-specific phototoxicity. Traditional strategies to fabricate controllable PS platforms rely on molecular design, which requires specific modification of each PS before PDT. Therefore, construction of a general tumor-responsive PDT platform with minimum ROS loss from endogenous antioxidant, typically glutathione (GSH), is highly desirable. Herein, MOF-199, a Cu(II) carboxylate-based metal-organic framework (MOF), is selected to serve as an inert carrier to load PSs with prohibited photosensitization during delivery. After cellular uptake, Cu (II) in the MOFs effectively scavenges endogenous GSH, concomitantly induces decomposition of MOF-199 to release the encapsulated PSs, and recovers their ROS generation. In vitro and in vivo experiments demonstrate highly effective cancer cell ablation and anticancer PDT with diminished normal cell phototoxicity. This strategy is generally applicable to PSs with both aggregation-induced emission and aggregation-caused quenching to implement activatable and enhanced image-guided PDT.
KW - activatable photodynamic therapy
KW - aggregation-induced emission
KW - glutathione
KW - metal-organic frameworks
KW - photosensitizers
UR - http://www.scopus.com/inward/record.url?scp=85068151861&partnerID=8YFLogxK
U2 - 10.1021/acsnano.9b01665
DO - 10.1021/acsnano.9b01665
M3 - Article
C2 - 31194910
AN - SCOPUS:85068151861
SN - 1936-0851
JO - ACS Nano
JF - ACS Nano
ER -