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

Autor: Pellosi DS; Laboratory of Phobiology and photomdicine, Department of Chemistry (FFCLRP), University of São Paulo, Av. dos Bandeirantes 3900, 14040-901, Vila Monte Alegre, Ribeirão Preto, Brazil., Calori IR; Research Nucleus of Photodynamic Therapy, Department of Chemistry, State University of Maringá, Av. Colombo 5790, 97020-900 Maringá, Brazil., de Paula LB; Laboratory of Phobiology and photomdicine, Department of Chemistry (FFCLRP), University of São Paulo, Av. dos Bandeirantes 3900, 14040-901, Vila Monte Alegre, Ribeirão Preto, Brazil., Hioka N; Research Nucleus of Photodynamic Therapy, Department of Chemistry, State University of Maringá, Av. Colombo 5790, 97020-900 Maringá, Brazil., Quaglia F; Laboratory of Drug Delivery, Department of Pharmacy, University of Napoli Federico II, Via Domenico Montesanto 49, 80131 Napoli, Italy., Tedesco AC; Laboratory of Phobiology and photomdicine, Department of Chemistry (FFCLRP), University of São Paulo, Av. dos Bandeirantes 3900, 14040-901, Vila Monte Alegre, Ribeirão Preto, Brazil. Electronic address: atedesco@usp.br.
Jazyk: angličtina
Zdroj: Materials science & engineering. C, Materials for biological applications [Mater Sci Eng C Mater Biol Appl] 2017 Feb 01; Vol. 71, pp. 1-9. Date of Electronic Publication: 2016 Sep 28.
DOI: 10.1016/j.msec.2016.09.064
Abstrakt: 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 6months 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 functionalized micelles showed higher internalization rates due biotin-mediated endocytosis, as demonstrated by competitive cellular uptake studies. Rhodamine 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 not 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.
(Copyright © 2016 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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