Labeling PLA-PEG nanocarriers with IR780: physical entrapment versus covalent attachment to polylactide
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ORIGINAL ARTICLE
Labeling PLA-PEG nanocarriers with IR780: physical entrapment versus covalent attachment to polylactide Marina Guimarães Carvalho Machado 1 & Gwenaelle Pound-Lana 1 & Maria Alice de Oliveira 1 & Elisa Gomes Lanna 1 & Márcia Célia Pacheco Fialho 1 & Ana Carolina Ferreira de Brito 2 & Ana Paula Moreira Barboza 2 & Rodrigo Dian de Oliveira Aguiar-Soares 3 & Vanessa Carla Furtado Mosqueira 1
# Controlled Release Society 2020
Abstract Near-infrared fluorescent dyes, such as IR780, are promising theranostics, acting as photosensitizers for photodynamic therapy and in vivo tracers in image-guided diagnosis. This work compared the uptake by macrophage-like cells of IR780 either physically associated or covalently attached to poly(D,L-lactide) (PLA) formulated as polymeric nanocapsules (NC) from a blend of PLA homopolymer and PLA-PEG block copolymer. The physicochemical characterization of both NC was conducted using asymmetric flow field-flow fractionation (AF4) analysis with static and dynamic light scattering and atomic force microscopy. The interaction of IR780 with serum proteins was evidenced by AF4 with fluorescence detection and flow cytometry in cell uptake studies. The average diameters of NC were around 120 nm and zeta potentials close to -40 mV for all NC. NC uptake by cells in different media and experimental conditions shows significantly lower fluorescence intensities for IR780 covalently linked to PLA and correspondingly low quantitative uptake. Different mechanisms of internalization were evidenced depending on the IR780 type of association to NC. Serum proteins mediate IR780 interaction with cells in a dose-dependent manner. Our results show that non-covalently linked IR780 was released from NC and accumulated in macrophage cells. Oppositely, IR780 conjugated to PLA provides stable association with NC, and its fluorescence is representative of cell uptake of the nanocarrier itself. This work strongly reinforces the importance of covalent attachment of a fluorescence dye such as IR780 to the nanocarrier to study their interaction with cells in vitro and to obtain reliable tracking in image-guided therapy. Keywords Nanocapsules, . Polymer conjugation, . Theranostics, . IR780, . Cell uptake, . Macrophage
Introduction Nanotechnology has developed considerably in recent decades, especially applied to the biomedical field, due to its potential to revolutionize the treatment of chronic degenera-
* Vanessa Carla Furtado Mosqueira [email protected]; [email protected] 1
Laboratory of Pharmaceutics and Nanotechnology, Pharmacy School, Federal University of Ouro Preto, Minas Gerais, Brazil
2
Laboratory of Microscopy, Department of Physics, Exact and Biological Sciences Institute, Federal University of Ouro Preto, Minas Gerais, Brazil
3
Department of Clinical Analysis, Pharmacy School and Nucleus of Research in Biological Sciences (NUPEB), Federal University of Ouro Preto, Minas Gerais, Brazil
tive conditions, such as cancer, cardiovascular dysfunctions, and inflammatory diseases wit
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