title: DH-I-180-3-mediated photodynamic therapy: biodistribution and tumor vascular damage.
abstract: 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.
authors.affiliation: Department of Microbiology, College of Medicine, Yonsei University, Seoul, Korea.
authors.forename: Dae-Seog
authors.initials: DS
authors.lastname: Lim
authors.forename: Si-Hwan
authors.initials: SH
authors.lastname: Ko
authors.forename: Chang-Hee
authors.initials: CH
authors.lastname: Lee
authors.forename: Woong-Shick
authors.initials: WS
authors.lastname: Ahn
authors.forename: Won-Young
authors.initials: WY
authors.lastname: Lee
mesh_terms: 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
chemical_list: C000607508:DH-I-180-3; D017319:Photosensitizing Agents; D011166:Porphyrins; D002734:Chlorophyll