title: Design of Pluronic-Based Formulation for Enhanced Redaporfin-Photodynamic Therapy against Pigmented Melanoma.
abstract: The therapeutic outcome of photodynamic therapy (PDT) with redaporfin (a fluorinated sulfonamide bacteriochlorin, F2BMet or LUZ11) was improved using Pluronic-based (P123, F127) formulations. Neither redaporfin encapsulated in Pluronic nor micelles alone exhibited cytotoxicity in a broad concentration range. Comprehensive in vitro studies against B16F10 melanoma cells showed that redaporfin-P123 micelles enhanced cellular uptake and increased oxidative stress compared with redaporfin-F127 or photosensitizer alone after short incubation times. ROS-sensitive fluorescent probes showed that the increased oxidative stress is due, at least in part, to a more efficient formation of hydroxyl radicals, and causes strong light-dose dependent apoptosis and necrosis. Tissue distribution and pharmacokinetic studies in tumor-bearing mice show that the Pluronic P123 formulation of redaporfin increases its bioavailability as well as the tumor-to-muscle and tumor-to-skin ratios, in comparison with Cremophor EL and Pluronic F127 formulations. Redaporfin in P123 was most successful in the PDT of C57BL/6J mice bearing subcutaneously implanted B16F10 melanoma tumors. Vascular-targeted PDT combining 1.5 mg kg(-1) redaporfin in P123 with a light dose of 74 J cm(-2) led to 100% complete cures (i.e., no tumor regrowth over one year post-treatment). This remarkable result reveals that modification of redaporfin with Pluronic block copolymers overcomes the resistance of melanoma cells to PDT possibly via increased tumor selectivity and enhanced ROS generation.
authors: Faculty of Chemistry, Jagiellonian University , 30-060 Kraków, Poland.
authors: Barbara
authors: B
authors: Pucelik
authors: CQC, Chemistry Department, University of Coimbra , Rua Larga, 3004-535 Coimbra, Portugal.
authors: Luis G
authors: LG
authors: Arnaut
authors: Faculty of Chemistry, Jagiellonian University , 30-060 Kraków, Poland.
authors: Grażyna
authors: G
authors: Stochel
authors: Faculty of Chemistry, Jagiellonian University , 30-060 Kraków, Poland.
authors: Janusz M
authors: JM
authors: Dąbrowski
mesh_terms: D000818:Animals; D008545:Melanoma; D051379:Mice; D008810:Mice, Inbred C57BL; D008823:Micelles; D010778:Photochemotherapy; D020442:Poloxamer; D011166:Porphyrins; D013449:Sulfonamides
chemical_list: D008823:Micelles; D011166:Porphyrins; D013449:Sulfonamides; D020442:Poloxamer; C000610760:redaporfin
keywords: bacteriochlorins; cancer; delivery vehicle; melanoma; photodynamic therapy; targeting