IR780-polymer conjugates for stable near-infrared labeling of biodegradable polyester-based nanocarriers

• Published in: European polymer journal Vol. 120; p. 109255
• Main Authors: de Oliveira, Maria Alice, Guimarães Carvalho Machado, Marina, Dias Silva, Sabrina Emanuelle, Leite Nascimento, Thais, Martins Lima, Eliana, Pound-Lana, Gwenaelle, Mosqueira, Vanessa Carla Furtado
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.11.2019; Elsevier BV
• Subjects: Alkynes; Biodegradability; Biodegradable materials; Click chemistry; Conjugates; Conjugation; Cycloaddition; Drug delivery systems; Dyes; Entrapment; Field flow fractionation; Fluorescence; Fluorescent dyes; Fluorescent label; Fractionation; High performance liquid chromatography; In vivo methods and tests; Labeling; Light scattering; Nanoparticles; Near infrared radiation; Near-infrared probe; Organic chemistry; Photodynamic therapy; Polylactide; Polymeric nanocarrier; Polymers; Proteins; Ring opening polymerization; Serum proteins; Studies; Field flow fractionation; Fluorescent label; Near-infrared probe; Click chemistry; Polymeric nanocarrier; Polylactide
• ISSN: 0014-3057; 1873-1945
• DOI: 10.1016/j.eurpolymj.2019.109255

[Display omitted] •The NIR probe IR780 was derivatized and covalently linked to polylactide.•The polymer-dye conjugate provides stable fluorescence labelling of nanocarriers.•Encapsulated IR780 leaks from the nanocarriers but not the polymer conjugate.•IR780 linked to PLA can be used for in vitro and in vivo fluorescence imaging. Near-infrared dyes are useful to monitor nanocarriers in vitro and in vivo and can serve as photosensitizers in cancer photodynamic therapy. However, strategies need to be developed to guarantee that the dye photophysical properties and loading within the drug delivery system remain stable for reliable tracking within biological systems. This work reports the facile chemical conjugation of the carbocyanine heptamethine near-infrared dye IR780 to polylactide for stable fluorescent labeling of biodegradable polyester nanocarriers. “Clickable” polylactide was synthesized via organocatalyzed ring opening polymerization of D,L-lactide with a cyclooctyne initiator. IR780 was derivatized and conjugated to polylactide via a one-pot copper-free azide-alkyne cycloaddition reaction. The synthetic strategy developed was effective to promote conjugation of the near-infrared fluorescent dye to polylactide, as confirmed by high performance liquid chromatography. Nanoparticles containing the dye–polymer conjugate were prepared by nanoprecipitation and characterized. Asymmetric flow field-flow fractionation with light scattering and fluorescence detection revealed that the near-infrared fluorescence of the nanoparticles remained stable and was not transferred to serum proteins. In contrast, significant transfer of the dye to serum proteins was evidenced when the dye was merely encapsulated in similar nanoparticles through physical entrapment. Confocal microscopy and fluorescence tomography imaging showed that the polymer-dye conjugate confers fluorescence properties to the NP suitable for further in vitro and in vivo pre-clinical studies.