Efficient gene delivery system mediated by cis-aconitate-modified chitosan-g-stearic acid micelles

Abstract

Cis-aconitate-modified chitosan-g-stearic acid (CA-CSO-SA) micelles were synthesized in this study to improve the gene transfection efficiency of chitosan-g-stearic acid (CSO-SA). The CA-CSO-SA micelles had a similar size, critical micelle concentration, and morphology, but their zeta potential and cytotoxicity were reduced compared with CSO-SA micelles. After modification with cis-aconitate, the CA-CSO-SA micelles could also compact plasmid DNA (pDNA) to form nanocomplexes. However, the DNA binding ability of CA-CSO-SA was slightly reduced compared with that of CSO-SA. The transfection efficiency mediated by CA-CSO-SA/pDNA against HEK-293 cells reached up to 37%, and was much higher than that of CSO-SA/pDNA (16%). Although the cis-aconitate modification reduced cellular uptake kinetics in the initial stages, the total amount of cellular uptake tended to be the same after 24 hours of incubation. An endocytosis inhibition experiment showed that the internalization mechanism of CA-CSO-SA/pDNA in HEK-293 cells was mainly via clathrin-mediated endocytosis, as well as caveolae-mediated endocytosis and macropinocytosis. Observation of intracellular trafficking indicated that the CSO-SA/pDNA complexes were trapped in endolysosomes, but CA-CSO-SA/pDNA was more widely distributed in the cytosol. This study suggests that modification with cis-aconitate improves the transfection efficiency of CSO-SA/pDNA.

The Janus Facet of Nanomaterials

“…The first section conveys information on probably the best-known and most intensively studied biosimilar NMs applied in biotechnology and medicine such as liposomes, chitosan, and poly(lactic-co-glycolic acid) (PLGA) nanoparticles. These biocompatible and biodegradable NMs represent wide potential use in delivering a large variety of drugs and therapeutics including small molecules, herbal medicines, genes, proteins, miRNAs, and oligonucleotides ([ 30 , 31 ] and references cited; [ 9 , 14 , 22 , 25 , 32 – 34 ]). The focus of the second section is on the possibility to conclude on trait-nanotoxicity relationships.…”

“…Numerous studies are concerned about the more specific and more efficient delivery of therapeutics by applying specific combinations of biocompatible and biodegradable NMs ([ 33 ] and reference cited). For recent examples we may conjecture more efficient transfection of nucleic acid-based therapeutics based on the modification of chitosan combined g-stearic acid micelles by cis-aconitate [ 34 ] or more effective targeted delivery of osthole by N-succinyl-chitosan nanoparticles coupled with low-density lipoprotein [ 22 ].…”

Effect of Anionic PEGylated Polypeptide on Gene Transfection Mediated by Glycolipid Conjugate Micelles

“…The incorporation of bovine serum albumin (isoelectric point value = 4.7) into CS/pDNA accelerated vector unpacking, thereby showing higher transfection efficiency than CS/pDNA counterparts . Our previous studies have also demonstrated that the addition of acids or negatively charged groups is beneficial to the gene transfection of CS/pDNA complexes. − …”

“…14 Our previous studies have also demonstrated that the addition of acids or negatively charged groups is beneficial to the gene transfection of CS/pDNA complexes. [14][15][16] Cationic-based delivery systems can be eliminated by the reticuloendothelial system (RES). 5 Therefore, polymers with covalently bound hydrophilic materials, such as poly(ethylene glycol) (PEG), were developed to prevent rapid clearance.…”