Photodynamic therapy of experimental B-16 melanoma in mice with tumor-targeted 5,10,15,20-tetraphenylporphin-loaded PEG-PE micelles.
Polyethylene glycol (PEG)-diacyl lipid micelles have been prepared by loading with the hydrophobic meso-5,10,15,20-tetraphenyl-21H,23H-porphine (TPP) and used for the photodynamic treatment of B-16 melanoma cells in vitro and in vivo. The use of PEG-PE micelles allowed for a 150-fold increased the solubilization of TPP, compared with the native drug. The average size of the PEG-PE micelles was in the range of 10-12 nm with a narrow size distribution. At 50 microg/ml of TPP in micelles with an irradiation intensity of 4.5-21.5 mW/cm(2), the viability of B-16 melanoma cells in vitro decreased in a fluence-dependent manner. A highly effective outcome of photodynamic therapy (PDT) with TPP-loaded PEG-PE micelles can be further increased by modifying such micelles with cancer-specific monoclonal antibody 2C5 to TPP-loaded micelles to tumor cells. TPP-containing 2C5-modified micelles provided the strongest phototoxic effect against B-16 cells in vitro compared with TPP-loaded plain micelles at the same TPP concentration. The association of TPP-loaded immuno-targeted micelles with melanoma cells was also studied by flow cytometry. An increase in cell association was found for 2C5-targeted micelles compared with non-targeted micelles. In vivo, the PDT treatment of subcutaneous melanoma-bearing C57BL/6 mice with 100 mW/cm(2) of 630 nm laser light 9 h after the administration of the micellar TPP (1 mg/kg of TPP) resulted in a significant inhibition of tumor growth. Compared with controls, the weight of postmortem tumors was approx. 3.5- and 7.5-fold smaller with TPP-loaded PEG-PE micelles and TPP-loaded PEG-PE 2C5-immunomicelles, respectively.
Skidan
Igor
I
Department of Pharmaceutical Sciences, Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, MA 02115, USA.
Dholakia
Parita
P
Torchilin
Vladimir
V
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D005260:Female; D005434:Flow Cytometry; D066298:In Vitro Techniques; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D009368:Neoplasm Transplantation; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011166:Porphyrins / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D012995:Solubility
C509964:5,10,15,20-tetraphenylporphyrin; D008823:Micelles; D010714:Phosphatidylethanolamines; D017319:Photosensitizing Agents; D011166:Porphyrins; C067972:dioleoyl-N-(monomethoxypolyethylene glycol succinyl)phosphatidylethanolamine; D011092:Polyethylene Glycols