Abstract
Gene therapy is a suitable alternative to chemotherapy due to the complications of drug resistance and toxicity of drugs, and is also known to reduce the occurrence of cellular mutation through the use of gene carriers. In this study, gene carrier nanoparticles with minimal toxicity and high transfection efficiency were fabricated from a biocompatible and biodegradable polymer, l-tyrosine polyurethane (LTU), which was polymerized from presynthesized desaminotyrosyl tyrosine hexyl ester (DTH) and polyethylene glycol (PEG), by using double emulsion and solvent evaporation techniques, resulting in the formation of porous nanoparticles, and then used to evaluate their potential biological activities through molecular controlled release and transfection studies. To assess cellular uptake and transfection efficiency, two model drugs, fluorescently labeled bovine serum albumin (FITC-BSA) and plasmid DNA-linear polyethylenimine (LPEI) complex, were successfully encapsulated in nanoparticles, and their transfection properties and cytotoxicities were evaluated in LX2 as a normal cell and in HepG2 and MCF7 as cancer cells. The morphology and average diameter of the LTU nanoparticles were confirmed using light microscopy, transmission electron microscopy, and dynamic light scattering, while confocal microscopy was used to validate the cellular uptake of FITC-BSA-encapsulated LTU nanoparticles. Moreover, the successful cellular uptake of LTU nanoparticles encapsulated with pDNA-LPEI and the high transfection efficiency, confirmed by gel electrophoresis and X-gal assay transfection, indicated that LTU nanoparticles had excellent cell adsorption ability, facilitated gene encapsulation, and showed the sustained release tendency of genes through transfection experiments, with an optimal concentration ratio of pDNA and LPEI of 1:10. All the above characteristics are ideal for gene carriers designed to transport and release drugs into the cytoplasm, thus facilitating effective gene therapy.
Highlights
IntroductionA number of attempts have been made to focus on the development of gene therapy to cure inheritable as well as congenital and acquired diseases [1,2,3,4]
Because the ability of biomaterials to adhere to cells is an important factor for conBecause the ability of biomaterials to adhere to cells is an important factor for confirmfirming biocompatibility, these results demonstrated that L-tyrosine polyurethane (LTU) NPs have the ability to efing biocompatibility, these results demonstrated that LTU NPs have the ability to effectively fectively adsorb to LX2 cells following incubation in a static state for 24 h
A novel biodegradable and biocompatible LTU was synthesized from polyethylene glycol (PEG), HMDI, and desaminotyrosyl tyrosine hexyl ester (DTH) as a biodegradable chain extender, and used to fabricate porous nanoparticles for efficient gene delivery using a double emulsion method
Summary
A number of attempts have been made to focus on the development of gene therapy to cure inheritable as well as congenital and acquired diseases [1,2,3,4]. It has been encumbered by stability problems, such as toxicity or host immune responses. It has been reported that non-viral gene delivery includes two types of common methods involving the use of nucleic acid complexed with cationic lipids (lipoplexes) or cationic polymers (polyplexes).
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