Multifunctional theranostic Pluronic mixed micelles improve targeted photoactivity of Verteporfin in cancer cells

Author(s)

Pellosi, Diogo Silva ; Calori, Italo Rodrigo ; de Paula, Leonardo Barcelos ; Hioka, Noboru ; Quaglia, Fabiana ; Tedesco, Antonio Claudio

• Document type: Journal article
• Source: Materials Science & Engineering C-Materials for Biological Applications; v. 71, p. 1-9, FEB 1 2017.
• Web of Science Citations: 16

Abstract

Nanotechnology development provides new strategies to treat cancer by integration of different treatment modalities in a single multifunctional nanoparticle. In this scenario, we applied the multifunctional Pluronic P123/F127 mixed micelles for Verteporfin-mediated photodynamic therapy in PC3 and MCF-7 cancer cells. Micelles functionalization aimed the targeted delivery by the insertion of biotin moiety on micelle surface and fluorescence image-based through rhodamine-B dye conjugation in the polymer chains. Multifunctional Pluronics formed spherical nanoparticulated micelles that efficiently encapsulated the photosensitizer Verteporfin maintaining its favorable photophysical properties. Lyophilized formulations were stable at least for 6 months and readily reconstituted in aqueous media. The multifunctional micelles were stable in protein-rich media due to the dual Pluronic mixed micelles characteristic: high drug loading capacity provided by its micellar core and high kinetic stability due its biocompatible shell. Biotin surface functiopalized micelles showed higher internalization rates due biotin-mediated endocytosis, as demonstrated by competitive cellular uptake studies. Rhoda mine B-tagged micelles allowed monitoring cellular uptake and intracellular distribution of the formulations. Confocal microscopy studies demonstrated a larger intracellular distribution of the formulation and photosensitizer, which could drive Verteporfin to act on multiple cell sites. Formulations were pot toxic in the dark condition, but showed high Verteporfin-induced phototoxicity against both cancer cell lines at low drug and light doses. These results point Verteporfin-loaded multifunctional micelles as a promising tool to further developments in photodynamic therapy of cancer. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 13/50181-1 - Use of drugs containing nanocarriers with photosensitizers and/or other active compounds applied to cell therapy and treatment of central nervous system disorders
• Grantee: Antonio Claudio Tedesco
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 16/00389-3 - MULTIFUNCTIONAL NANOPARTICLES FOR SITE-ESPECIFIC DELIVERY OF TEMOZOLOMIDE® AND VERTEPORFIN® FOR COMBINATION THERAPY OF BRAIN TUMORS
• Grantee: Diogo Silva Pellosi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 15/18684-9 - Use of drugs containing nanocarriers with photosensitizers and/or other active compounds applied to cell therapy and treatment of central nervous system disorders
• Grantee: Leonardo Barcelos de Paula
• Support Opportunities: Scholarships in Brazil - Post-Doctoral