Antiangiogenic photodynamic therapy with targeted liposomes.
Antiangiogenic photodynamic therapy (PDT) is a promising modality for cancer treatment, since it causes efficient cutoff of oxygen and nutrients to the tumor cells and thus indirectly eradicates the tumor cells. For the improvement of therapeutic efficacy of antiangiogenic PDT by using a photosensitizer benzoporphyrin derivative monoacid ring A (BPD-MA) in a liposomal formulation, we endowed the liposomes with an active-targeting probe, Ala-Pro-Arg-Pro-Gly (APRPG), a peptide specific for angiogenic endothelial cells. APRPG-PEG-modified liposomal BPD-MA (APRPG-PEG-LipBPD-MA) accumulated in tumor tissues to a similar extent as PEG-LipBPD-MA at 3-h postinjection. In contrast, APRPG-PEG-LipBPD-MA strongly suppressed tumor growth by PDT treatment, but PEG-LipBPD-MA did not. This finding suggests that antiangiogenic PDT with targeted liposomes is an efficient modality for tumor treatment, whereas PEG-modified nontargeted liposomes are not suitable as a carrier of photosensitizers. The reason for the observed ineffectiveness of PEG-LipBPD-MA is as follows: In the case of PDT, the amount of photosensitizer bound to or taken up into the target cells during the time interval between injection of the agent and laser irradiation is critical, rather than the total amount of photosensitizer in tumor tissue. Therefore, active-targeting technology is quite useful for antiangiogenic PDT.
Oku
Naoto
N
Department of Medical Biochemistry, University of Shizuoka School of Pharmaceutical Sciences, Shizuoka, Japan.
Ishii
Takayuki
T
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008081:Liposomes; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010778:Photochemotherapy; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011166:Porphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014018:Tissue Distribution
D020533:Angiogenesis Inhibitors; D008081:Liposomes; D011166:Porphyrins; D011092:Polyethylene Glycols