Synthesis and Intracellular Uptake of Rhodamine–Nucleolipid Conjugates into a Nanoemulsion Vehicle
Résumé
Neurodegenerative diseases represent some of the greatest challenges for both basic science and clinical medicine. Due to their prevalence and lack of known biochemical-based treatments, these complex pathologies represent an increasing societal cost. Increasing genetic and neuropathological evidence point that lysosomal impairment may be a common factor linking these diseases, laying the development of therapeutic strategies aimed at restoring lysosomal function. Here, we propose the design and synthesis of a nucleolipid conjugate as a non-viral chemical nanovector to target specifically neuronal cells and intracellular organelles. Herein, a thymidine appropriately substituted to increase its lipophilicity, was used as a model nucleoside and a fluorophore moiety, covalently bound to the nucleoside, allowed to monitor the nucleolipid's internalization in vitro. In order 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 bring drugs to restore lysosomal impaired function.
Domaines
Chimie organique
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