Synthesis and Intracellular Uptake of Rhodamine–Nucleolipid Conjugates into a Nanoemulsion Vehicle

Anthony Cunha, Geoffrey Prévot, Yannick Mousli, Philippe Barthélémy, Sylvie Crauste-Manciet, Benjamin Dehay, Valérie Desvergnes
ACS Omega. 2020-03-12; 5(11): 5815-5823
DOI: 10.1021/acsomega.9b03992

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Cunha A(1)(2)(3), Prévot G(1), Mousli Y(1), Barthélémy P(1), Crauste-Manciet S(1), Dehay B(2)(3), Desvergnes V(1).

Author information:
(1)Université de Bordeaux, INSERM, U1212, CNRS UMR 5320, ARNA, ARN: Régulations Naturelle et Artificielle, ChemBioPharm, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.
(2)Université de Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, F-33076 Bordeaux, France.
(3)CNRS, Institut des Maladies Neurodégénératives, UMR 5293, Centre Broca Nouvelle-Aquitaine, 146 rue Léo Saignat, 33076 Bordeaux Cedex, France.

Neurodegenerative diseases represent some of the greatest challenges for both basic science and clinical medicine. Due to their prevalence and the lack of known biochemical-based treatments, these complex pathologies result in an increasing societal cost. Increasing genetic and neuropathological evidence
indicates that lysosomal impairment may be a common factor linking these diseases, demanding the development of therapeutic strategies aimed at restoring the lysosomal function. Here, we propose the design and synthesis of a nucleolipid conjugate as a nonviral chemical nanovector to specifically target neuronal cells and intracellular organelles. Herein, thymidine, appropriately substituted to increase its lipophilicity, was used as a model nucleoside and a fluorophore moiety, covalently bound to the nucleoside, allowed the monitoring of
nucleolipid internalization in vitro. To improve nucleolipid protection and cellular uptake, these conjugates were formulated in nanoemulsions. In vitro biological assays demonstrated cell uptake- and internalization-associated colocalization with lysosomal markers. Overall, this nucleolipid-nanoemulsion-based formulation represents a promising drug-delivery tool to target the central nervous system, able to deliver drugs to restore the impaired lysosomal function.

Copyright © 2020 American Chemical Society.


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