Intracellular target for photosensitization in cancer antiangiogenic photodynamic therapy mediated by polycation liposome.
Previous study indicated that antiangiogenic photodynamic therapy (PDT), laser irradiation at 15 min post-injection of photosensitizer in vivo, is effective for cancer treatment, and a photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA), encapsulated in polycation liposomes (PCLs), liposomes modified with cetylated polyethylenimine (cetyl-PEI), is more effective than BPD-MA encapsulated in non-modified liposomes [Cancer 97 (2003) 2027]. In the present study, we examined intracellular distribution of BPD-MA. BPD-MA encapsulated in liposomes or in PCLs was incubated with human endothelial cell line ECV304 cells or human umbilical vein endothelial cells (HUVECs), and monitored the intracellular distribution of BPD-MA by confocal laser scan microscopy. BPD-MA was taken up time-dependently into the cells and was distributed in not only cytoplasmic area but also intranuclear region. The enhanced uptake of BPD-MA was observed by the PCL formulation. Intracellular distribution of polycation was monitored by using fluorescein isothiocyanate-labeled cetyl-PEI (cetyl-PEI-FITC) and was colocalized with BPD-MA. Cytoplasmic BPD-MA distribution was partly overlapped with that of rhodamine 123, a mitochondrial fluorostaining probe, suggesting that mitochondrial photosensitization as well as nuclear photosensitization, is involved in the antiangiogenic PDT treatment.
Takeuchi
Yoshito
Y
Department of Medical Biochemistry and COE Program in the 21st Century, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Shizuoka 422-8526, Japan.
Ichikawa
Kanae
K
Yonezawa
Sei
S
Kurohane
Kohta
K
Koishi
Takayuki
T
Nango
Mamoru
M
Namba
Yukihiro
Y
Oku
Naoto
N
D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008081:Liposomes; D018613:Microscopy, Confocal; D008928:Mitochondria / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000628:therapy; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D011094:Polyethyleneimine / Q000737:chemistry / Q000493:pharmacokinetics; D011166:Porphyrins / Q000737:chemistry / Q000493:pharmacokinetics*; D013997:Time Factors
D008081:Liposomes; D017319:Photosensitizing Agents; D011166:Porphyrins; C504224:benzoporphyrin D; D011094:Polyethyleneimine