title: Solubilization of poorly soluble PDT agent, meso-tetraphenylporphin, in plain or immunotargeted PEG-PE micelles results in dramatically improved cancer cell killing in vitro.
abstract: Poorly soluble photodynamic therapy (PDT) agent, meso-tetratphenylporphine (TPP), was effectively solubilized using non-targeted and tumor-targeted polymeric micelles prepared of polyethylene glycol/phosphatidyl ethanolamine conjugate (PEG-PE). Encapsulation of TPP into PEG-PE-based micelles and immunomicelles (bearing an anti-cancer monoclonal 2C5 antibody) resulted in significantly improved anticancer effects of the drug at PDT conditions against murine (LLC, B16) and human (MCF-7, BT20) cancer cells in vitro. For this purpose, the cells were incubated for 6 or 18 h with the TPP or TPP-loaded PEG-PE micelles/immunomicelles and then light-irradiated for 30 min. The phototoxic effect depended on the TPP concentration and specific targeting by immunomicelles. An increased level of apoptosis was shown in the PDT-treated cultures. The attachment of the anti-cancer 2C5 antibodies to TPP-loaded micelles provided the maximum level of cell killing at a given time. The results of this study showed that TPP-containing PEG-PE micelles may represent a useful formulation of the photosensitizer for practical PDT.
authors.affiliation: Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
authors.forename: Aruna
authors.initials: A
authors.lastname: Roby
authors.forename: Suna
authors.initials: S
authors.lastname: Erdogan
authors.forename: Vladimir P
authors.initials: VP
authors.lastname: Torchilin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D016503:Drug Delivery Systems; D004355:Drug Stability; D005079:Excipients; D006801:Humans; D051379:Mice; D008823:Micelles; D010316:Particle Size; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D011092:Polyethylene Glycols; D011166:Porphyrins / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D005079:Excipients; D008823:Micelles; D017319:Photosensitizing Agents; D011166:Porphyrins; D011092:Polyethylene Glycols; C049692:tetraphenylporphine