DH-I-180-3-mediated photodynamic therapy: biodistribution and tumor vascular damage.
An important goal of photodynamic therapy (PDT) for treatment of various cancers is to shorten PDT-performing time and simultaneously enhance PDT efficacy. Here, we investigated the nontumor tissue distribution of and the tumor vascular damage caused by a new photosensitizer, DH-I-180-3, in mice with implanted EMT6 mammary tumor cells. In addition, we performed cell-based assays to evaluate the basic antitumor effect of DH-I-180-3/PDT in EMT6 cells. After administration of PDT, the type of cell death was characterized to be apoptosis, and a change in the mitochondrial membrane potential was also observed within minutes. On the other hand, tumor growth was remarkably retarded in vivo in mice that received DH-I-180-3/PDT, compared with mice in the control group, which were exposed to light irradiation alone. Finally, tumors in some mice nearly healed. The antitumor drug reached a maximum concentration approximately 3 h after administration. However, PDT was most effective when there was substantial accumulation of DH-I-180-3 in the tumor vasculature and in healthy tissue. The histological demonstration provided further evidence of tumor vascular damage. On the basis of these findings, we suggest that PDT with the photosensitizer DH-I-180-3 induces vascular damage with blood vessel shutdown, in addition to direct killing of tumor cells, in mice.
Lim
Dae-Seog
DS
Department of Microbiology, College of Medicine, Yonsei University, Seoul, Korea.
Ko
Si-Hwan
SH
Lee
Chang-Hee
CH
Ahn
Woong-Shick
WS
Lee
Won-Young
WY
D000818:Animals; D002734:Chlorophyll / Q000031:analogs & derivatives; D053938:DNA Fragmentation / Q000187:drug effects* / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D008027:Light; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011166:Porphyrins / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects / Q000528:radiation effects; D014407:Tumor Cells, Cultured
C000607508:DH-I-180-3; D017319:Photosensitizing Agents; D011166:Porphyrins; D002734:Chlorophyll