周林副教授、魏少華教授課題組在MOLECULAR PHARMACEUTICS發(fā)表研究論文
Multiple Functions Integrated inside a Single Molecule for Amplification of Photodynamic Therapy Activity
Shi, XQ (Shi, Xianqing)[ 1 ] ; Zhan, QC (Zhan, Qichen)[ 1 ] ; Li, YQ (Li, Yanqing)[ 1 ] ; Zhou, L (Zhou, Lin)[ 1 ]*（周林）; Wei, SH (Wei, Shaohua)[ 1,2 ]*（魏少華）
[ 1 ] Nanjing Normal Univ, Key Lab Appl Photochem, Jiangsu Collaborat Innovat Ctr Biomed Funct Mat, Coll Chem & Mat Sci,Jiangsu Key Lab Biofunct Mat, Nanjing 210023, Jiangsu, Peoples R China
[ 2 ] Yancheng Inst Technol, Sch Chem & Chem Engn, Yancheng 224051, Jiangsu, Peoples R China
MOLECULAR PHARMACEUTICS，202001,17(1),190-201
Nitric oxide (NO) can play both prosurvival and prodeath roles in photodynamic therapy (PDT). The generation efficiency of peroxynitrite anions (ONOO-), by NO and superoxide anions (O-2(center dot-)), significantly influenced the outcome. Reports indicated that such efficiency is closely related to the distance between NO and O-2(center dot-). Thus, in this manuscript, L-arginine (Arg) ethyl ester-modified zinc phthalocyanine (Arg-ZnPc) was designed and synthesized as a photosensitizer (PS) and NO donor. Post light irradiation, the guanido of Arg-ZnPc can be effectively oxidized by the generated reactive oxygen species (ROS) in the PDT process to release NO. Such a strategy could ensure O-2(center dot-) and NO generation in the same place at the same time to guarantee effective ONOO- formation. In addition, NO has other multiple synergistic cancer treatment functions, including tumor tissue vasodilatation for drug extravasation promotion, P-glycoprotein (P-gp) downregulation for drug efflux inhibition, and glutathione depletion for cancer cell endogenous antioxidant defense destruction. In vitro and in vivo results indicated that the effective ONOO- formation and multiple functions of Arg-ZnPc could synergistically enhance its PDT activity and ensure satisfactory cancer treatment outcome.
文章鏈接：
https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.9b00893
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