Novel cationic 6-lauroxyhexyl lysinate modified poly(lactic acid)–poly(ethylene glycol) nanoparticles enhance gene transfection

The leading principle of non-viral delivery systems for gene therapy is to mediate high levels of gene expression with low cytotoxicity. Nowadays, biodegradable nanoparticles formulated with poly(lactic acid)–poly(ethylene glycol) (PLA–PEG) were wildly developed. However, the relative lower gene transfection efficiency and higher cytotoxicity still remained critical problems. To address these limitations, PLA–PEG nanoparticles have been composited with other components in their formulation. Here, a novel cationic lipid, 6-lauroxyhexyl lysinate (LHLN), was fabricated onto PLA–PEG nanoparticles as a charge modifier to improve the transfection efficiency and cytotoxicity. The obtained cationic LHLN modified PLA–PEG nanoparticles (LHLN–PLA–PEG NPs) could condense pDNA thoroughly via electrostatic force, leading to the formation of the LHLN–PLA–PEG NPs/pDNA complexes (NPs/DNA complexes). The nanoparticles obtained have been characterized in relation to their physicochemical and biological properties, and the results are extremely promising in terms of low cell toxicity and high transfection efficiency. These results indicated that the novel cationic LHLN modified PLA–PEG nanoparticles could enhance gene transfection in vitro and hold the potential to be a promising non-viral nanodevice.

LHLN was fabricated onto PLA–PEG nanoparticles as a charge modifier to obtain LHLN–PLA–PEG NPs which could condense pDNA thoroughly and showed higher transfection efficiency and lower cytotoxicity than Lipofectamine.Figure optionsDownload high-quality image (66 K)Download as PowerPoint slideResearch highlights
► A novel cationic surfactant, LHLN was synthesized.
► LHLN was successfully fabricated onto PLA–PEG nanoparticles.
► LHLN modified PLA–PEG nanoparticles could condense DNA thoroughly into NPs/DNA complexes.
► Results of cell toxicity and transfection efficiency are extremely promising.
► LHLN–PLA–PEG NPs hold the potential to be one of the most promising candidates of non-viral nanodevice.