Photodynamic efficiency of a chlorophyll-a derivative in vitro and in vivo.
This paper reports the antitumor activity of a chlorophyll-a derivative, 2-[1-hydroxyethyl]-2-devinylpyropheophorbide-a (HEPa). Photophysical characteristics of HEPa were measured. And its cytotoxicity, intracellular localization, biodistribution, efficiency of photodynamic therapy (PDT), histological analysis were investigated using human bile duct carcinoma cells (QBC-939) and QBC-939 tumor bearing BABL/c nude mice as animal model. The results showed that HEPa was localized mainly within the cytoplasmic region and partially in lysosome. Biodistribution of HEPa in QBC-939 tumor bearing BABL/c nude mice showed its fast rate of clearance and high tumor selectivity. In vitro, HEPa had low dark toxicity and high photoxicity against QBC-939 cells. The inhibition rate of QBC-939 tumor could increase up to 92.3%, and H&E staining confirmed that HEPa could cause serious damage to the tumor with light dose of 100J/cm(2), implying that HEPa has potential to be a new antitumor candidate for photodynamic therapy (PDT).
Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200433, China.
Xiang-Hua
XH
Zhang
Department of Pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai 201620, China.
Li-Jun
LJ
Zhang
Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200433, China.
Jing-Jian
JJ
Sun
Shanghai Xianhui Pharmaceutical Co., Ltd., Shanghai 200433, China.
Yi-Jia
YJ
Yan
Shanghai Xianhui Pharmaceutical Co., Ltd., Shanghai 200433, China.
Li-Xin
LX
Zhang
Shanghai Xianhui Pharmaceutical Co., Ltd., Shanghai 200433, China.
Na
N
Chen
Department of Pharmaceutical Science & Technology, College of Chemistry and Biology, Donghua University, Shanghai 201620, China. Electronic address: zlchen1967@qq.com.
Zhi-Long
ZL
Chen
D000818:Animals; D045744:Cell Line, Tumor; D002734:Chlorophyll / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use* / Q000633:toxicity; D000077194:Chlorophyll A; D003624:Darkness; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010778:Photochemotherapy; D026082:Singlet Oxygen / Q000032:analysis; D013056:Spectrophotometry, Ultraviolet; D014018:Tissue Distribution / Q000187:drug effects
D002734:Chlorophyll; D026082:Singlet Oxygen; D000077194:Chlorophyll A
Chlorophyll-a; HEPa; Photodynamic therapy; Photosensitizer; Tumor