ABSTRACT
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.
Subject(s)
Photosensitizing Agents/pharmacokinetics , Porphyrins/pharmacokinetics , Cells, Cultured , Endothelium, Vascular/cytology , Endothelium, Vascular/metabolism , Humans , Liposomes , Microscopy, Confocal , Mitochondria/metabolism , Neovascularization, Pathologic/therapy , Photochemotherapy , Photosensitizing Agents/chemistry , Polyethyleneimine/chemistry , Polyethyleneimine/pharmacokinetics , Porphyrins/chemistry , Time FactorsABSTRACT
To construct a novel drug delivery carrier that possesses high therapeutic efficacy with low dosage, we designed polyethylenimine-modified liposome (polycation liposome, PCL) and examined the entrapment of photosensitizer, benzoporphyrin derivative monoacid ring A (BPD-MA), for antiangiogenic photodynamic therapy (PDT). Photosensitizer entrapped in PCLs showed enhanced phototoxicity for a human vascular endothelial cell line, ECV304, in comparison with that for nonmodified control liposome. Interestingly, phototoxicity of control liposomal BPD-MA was suppressed in the presence of serum, but PCL maintained the phototoxicity in the presence of serum following PCL-mediated PDT treatment due to the stability of PCL and the reduced detachment of encapsulated photosensitizer from liposome to serum. In fact, PCL enhanced the uptake level of BPD-MA to ECV304 cells despite the presence or absence of serum. Since polycation modification enhances bioavailability of the liposomal photosensitizer and this property is maintained in the presence of serum, PCL would be useful for antiangiogenic PDT.
