Pentalysine beta-carbonylphthalocyanine zinc: an effective tumor-targeting photosensitizer for photodynamic therapy.
Unsymmetrical phthalocyanine derivatives have been widely studied as photosensitizers for photodynamic therapy (PDT), targeting various tumor types. However, the preparation of unsymmetrical phthalocyanines is always a challenge due to the presence of many possible structural isomers. Herein we report a new unsymmetrical zinc phthalocyanine, pentalysine beta-carbonylphthalocyanine zinc (ZnPc-(Lys)(5)), that was prepared in large quantity and high purity. This is a water-soluble cationic photosensitizer and maintains a high quantum yield of singlet oxygen generation similar to that of unsubstituted zinc phthalocyanine (ZnPc). Compared with anionic ZnPc counterparts, ZnPc-(Lys)(5) shows a higher level cellular uptake and 20-fold higher phototoxicity toward tumor cells. Pharmacokinetics and PDT studies of ZnPc-(Lys)(5) in S180 tumor-bearing mice showed a high ratio of tumor versus skin retention and significant tumor inhibition. This new molecular framework will allow synthetic diversity in the number of lysine residues incorporated and will facilitate future QSAR studies.
Chen
Zhuo
Z
Graduate University of Chinese Academy of Sciences, 19 Yuquan Road, Shijingshan District, Beijing 100049, China.
Zhou
Shanyong
S
Chen
Jincan
J
Deng
Yicai
Y
Luo
Zhipu
Z
Chen
Hongwei
H
Hamblin
Michael R
MR
Huang
Mingdong
M
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D002460:Cell Line; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity*; D054833:Isoindoles; D020014:K562 Cells; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D009842:Oligopeptides / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity*; D009942:Organometallic Compounds / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000627:therapeutic use / Q000633:toxicity*; D026082:Singlet Oxygen / Q000378:metabolism; D017967:Zinc Compounds
D000970:Antineoplastic Agents; D007211:Indoles; D054833:Isoindoles; D009842:Oligopeptides; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; D017967:Zinc Compounds; C551983:pentalysine beta-carbonylphthalocyanine zinc; C052159:Zn(II)-phthalocyanine; D026082:Singlet Oxygen; C026591:pentalysine; C013647:phthalocyanine
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