Enhanced in vivo antitumor efficacy of poorly soluble PDT agent, meso-tetraphenylporphine, in PEG-PE-based tumor-targeted immunomicelles.
Poorly soluble photosensitizer, meso-tetraphenylporphine (TPP), was solubilized using the polymeric micelles prepared from polyethylene glycol-phosphatidyl ethanolamine conjugate (PEG-PE). TPP-loaded PEG-PE micelles have been additionally modified with tumor-specific monoclonal 2C5 antibody (mAb 2C5), which resulted in significantly improved anticancer effect of the drug under the PDT conditions against murine Lewis lung carcinoma (LLC) In vivo in female C57BL/6 mice. Fourteen days after tumor inoculation, the mice with more than 2 mm diameter tumors were given an intravenous injection of 1 mg/kg of free TPP or TPP loaded into control PEG-PE micelles or into mAb 2C5-PEG-PE tumor-targeted immunomicelles. Twenty-four hours after the administration, the animals were anesthetized, and tumor sites were illuminated with light (630 nm) for 12 min. Microscopic evaluation of tumor response was conducted in some mice 24 h after light irradiation, and tumor size was followed in the remaining animals for another 35 days. The attachment of mAb 2C5 to TPP-loaded immunomicelles provided the maximum level of tumor growth inhibition. Enhanced tumor accumulation of TPP-loaded mAb 2C5-PEG-PE-immunomicelles was confirmed by gamma-imaging studies. The modification of the TPP-loaded polymeric micelles with tumor-specific antibodies could be used as a general approach to enhance the efficacy of PDT.
Roby
Aruna
A
Department of Pharmaceutical Sciences and Center for Pharmaceutical Biotechnology and Nanomedicine, Northeastern University, Boston, Massachusetts 02115, USA.
Erdogan
Suna
S
Torchilin
Vladimir P
VP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D010778:Photochemotherapy; D011166:Porphyrins / Q000627:therapeutic use*; D011877:Radionuclide Imaging
D008823:Micelles; D011166:Porphyrins; C049692:tetraphenylporphine