Positively charged phthalocyanine-arginine conjugates as efficient photosensitizer for photodynamic therapy.
Positively charged drugs usually have enhanced water solubility, cellular uptake efficiency and anticancer activity. However, the common quaternized and protonated cationic photosensitizers both have some drawbacks such as needing potentially dangerous agents for preparation and easily being deprotonated in alkaline circumstance. Arginine is unique among the amino acids as its guanidine group has exceptionally high basicity in aqueous solution, which may make it positively charged in a wide range of pH. In this paper, two arginine substituted zinc phthalocyanines (ArgEZnPc and ArgZnPc) were reported. They can be positively charged in the range of pH 5-9. Moreover, the photobiological, photochemical properties, subcellular localization, and in vitro anticancer activities of the them were also carried out. The results show that ArgZnPc may be not a good photosensitizer because of its poor photobiological activities though it is positively charged in a wide range of pHs. This may be attributed to the formation of inner salts between guanidine and carboxyl groups of ArgZnPc, which weakens its photobiological and in vitro anticancer activity. While in contrast, ArgEZnPc shows preferential localization in the lysosomes of HeLa cells, exhibits high water solubility, excellent1O2and intracellular reactive oxygen species generation efficiency as well as high in vitro anticancer activity, making it a promising photosensitizer for photodynamic therapy.
Research Institute of Forestry New Technology, CAF, Xiangshan Road, Beijing 100091, China; Institute of Chemical Industry of Forest Products, Key Lab of Biomass Energy and Material, Jiangsu Province, National Engineering Lab. For Biomass Chemical Utilization, Key and Open Lab. of Forest Chemical Engineering, SFA, Chinese Academy of Forestry, No. 16, Suojin 5th Village, Nanjing 210042, China.
Ao
A
Wang
School of Chemistry and Materials Science, Jiangsu Collaborative Innovation Centre of Biomedical Functional Materials, Key Laboratory of Applied Photochemistry, Nanjing Normal University, Wenyuan Road No. 1, Nanjing 210023, China.
Rongrong
R
Zhou
School of Chemistry and Materials Science, Jiangsu Collaborative Innovation Centre of Biomedical Functional Materials, Key Laboratory of Applied Photochemistry, Nanjing Normal University, Wenyuan Road No. 1, Nanjing 210023, China.
Lin
L
Zhou
Research Institute of Forestry New Technology, CAF, Xiangshan Road, Beijing 100091, China; Institute of Chemical Industry of Forest Products, Key Lab of Biomass Energy and Material, Jiangsu Province, National Engineering Lab. For Biomass Chemical Utilization, Key and Open Lab. of Forest Chemical Engineering, SFA, Chinese Academy of Forestry, No. 16, Suojin 5th Village, Nanjing 210042, China. Electronic address: sunkang0226@163.com.
Kang
K
Sun
Research Institute of Forestry New Technology, CAF, Xiangshan Road, Beijing 100091, China; Institute of Chemical Industry of Forest Products, Key Lab of Biomass Energy and Material, Jiangsu Province, National Engineering Lab. For Biomass Chemical Utilization, Key and Open Lab. of Forest Chemical Engineering, SFA, Chinese Academy of Forestry, No. 16, Suojin 5th Village, Nanjing 210042, China.
Jianchun
J
Jiang
School of Chemistry and Materials Science, Jiangsu Collaborative Innovation Centre of Biomedical Functional Materials, Key Laboratory of Applied Photochemistry, Nanjing Normal University, Wenyuan Road No. 1, Nanjing 210023, China. Electronic address: shwei@njnu.edu.cn.
Shaohua
S
Wei
D001120:Arginine / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000737:chemistry*; D054833:Isoindoles; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
D007211:Indoles; D054833:Isoindoles; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D001120:Arginine; C013647:phthalocyanine
Arginine; Guanidine; Inner salt; Photodynamic therapy; Photosensitizer; Positively charged phthalocyanine