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2021

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cc-by (c) Eva Aubets Gil, et al, 2021
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/182280

Synthesis and validation of DOPY: A new gemini dioleylbispyridinium based amphiphile for nucleic acid transfection

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https://doi.org/10.1016/j.ejpb.2021.05.016

Abstract

Nucleic acids therapeutics provide a selective and promising alternative to traditional treatments for multiple genetic diseases. A major obstacle is the development of safe and efficient delivery systems. Here, we report the synthesis of the new cationic gemini amphiphile 1,3-bis[(4-oleyl-1-pyridinio)methyl]benzene dibromide (DOPY). Its transfection efficiency was evaluated using PolyPurine Reverse Hoogsteen hairpins (PPRHs), a nucleic acid tool for gene silencing and gene repair developed in our laboratory. The interaction of DOPY with PPRHs was confirmed by gel retardation assays, and it forms complexes of 155 nm. We also demonstrated the prominent internalization of PPRHs using DOPY compared to other chemical vehicles in SH-SY5Y, PC-3 and DF42 cells. Regarding gene silencing, a specific PPRH against the survivin gene delivered with DOPY decreased survivin protein levels and cell viability more effectively than with N-[1-(2,3-Dioleoyloxy)propyl]-N,N,N-trimethylammonium methylsulfate (DOTAP) in both SH-SY5Y and PC-3 cells. We also validated the applicability of DOPY in gene repair approaches by correcting a point mutation in the endogenous locus of the dhfr gene in DF42 cells using repair-PPRHs. All these results indicate both an efficient entry and release of PPRHs at the intracellular level. Therefore, DOPY can be considered as a new lipid-based vehicle for the delivery of therapeutic oligonucleotides.

Subject

Càncer, Teràpia genètica, Expressió gènica

Subject (English)

Cancer, Gene therapy, Gene expression

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Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)
Articles publicats en revistes (Bioquímica i Fisiologia)
Articles publicats en revistes (Farmàcia, Tecnologia Farmacèutica i Fisicoquímica)

Citation

AUBETS GIL, Eva, et al. Synthesis and validation of DOPY: A new gemini dioleylbispyridinium based amphiphile for nucleic acid transfection. European Journal of Pharmaceutics and Biopharmaceutics. 2021. Vol. 165, num. 279-292. ISSN 0939-6411. [consulted: 9 of June of 2026]. Available at: https://hdl.handle.net/2445/182280

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