Enantiomeric lysine-based cationic lipids: Design, synthesis, and characterization for in vitro gene delivery

Q2 Pharmacology, Toxicology and Pharmaceutics

OpenNano Pub Date : 2026-03-01 Epub Date: 2025-12-28 DOI:10.1016/j.onano.2025.100280

Berenice Erendira Oseguera-Guerra , Oliver Lopez-Villegas , Manuel Román-Aguirre , Alfredo Aguilar-Elguezabal , Raúl Loera-Valencia , Silvia Lorena Montes-Fonseca

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引用次数: 0

Abstract

Nucleic acid delivery is crucial for gene therapy, vaccination, and cancer treatment. Despite advances in cationic lipid-based vectors, their transfection efficiency is often limited by structural complexity. In this study, we synthesized lysine-based cationic lipids by esterifying d- or l-lysine with alcohols of varying chain lengths. The compounds were characterized by infrared spectroscopy and mass spectrometry, incorporated into liposomes, and evaluated for transfection efficiency, particle size, morphology, and cytotoxicity in vitro. Transfection performance increased with chain length, peaking at 20 carbons, with no significant differences between d- and l-enantiomers. Compared to Lipofectamine 2000, the optimized liposomes showed superior gene delivery while preserving cell viability. They displayed predominantly spherical to oval morphologies, particle sizes of 30–130 nm, and negligible cytotoxicity. These results suggest lysine-based cationic lipids are promising, safe, and effective nonviral vectors for nucleic acid delivery.

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基于赖氨酸的阳离子脂质对映体：设计、合成和表征体外基因传递

核酸传递对基因治疗、疫苗接种和癌症治疗至关重要。尽管阳离子脂质载体取得了进展，但其转染效率往往受到结构复杂性的限制。在本研究中，我们通过将d-赖氨酸或l-赖氨酸与不同链长的醇酯化合成了基于赖氨酸的阳离子脂质。通过红外光谱和质谱对化合物进行了表征，并将其纳入脂质体中，并在体外对转染效率、粒径、形态和细胞毒性进行了评估。转染性能随着链长的增加而增加，在20个碳处达到峰值，d-和l-对映体之间没有显著差异。与Lipofectamine 2000相比，优化后的脂质体在保持细胞活力的同时具有更好的基因传递能力。它们主要呈球形到椭圆形形态，粒径为30-130 nm，细胞毒性可以忽略不计。这些结果表明，基于赖氨酸的阳离子脂质是一种有前途的、安全的、有效的核酸传递的非病毒载体。

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来源期刊

OpenNano Medicine-Pharmacology (medical)

CiteScore

4.10

自引率

0.00%

发文量

审稿时长

50 days

期刊介绍： OpenNano is an internationally peer-reviewed and open access journal publishing high-quality review articles and original research papers on the burgeoning area of nanopharmaceutics and nanosized delivery systems for drugs, genes, and imaging agents. The Journal publishes basic, translational and clinical research as well as methodological papers and aims to bring together chemists, biochemists, cell biologists, material scientists, pharmaceutical scientists, pharmacologists, clinicians and all others working in this exciting and challenging area.