Effect of Proteins with Different Isoelectric Points on the Gene Transfection Efficiency Mediated by Stearic Acid Grafted Chitosan Oligosaccharide Micelles

Abstract

A stearic acid-grafted chitosan oligosaccharide (CS-SA) micelle has been demonstrated as an effective gene carrier in vitro and in vivo. Although being advantageous for DNA package, protection, and excellent cellular internalization, a CS-SA based delivery system may lead to difficulties in the dissociation of polymer/DNA complexes in intracells. In this research, bovine serum albumin (BSA) with a different isoelectric point value (4.7, 6.0 and 9.3) was synthesized and incorporated into a CS-SA based gene delivery system. CS-SA/DNA binary complexes and CS-SA/BSA/DNA ternary complexes were then prepared and characterized. The binding ability of the CS-SA vector with DNA was not affected by the incorporation of BSA. However, referring to the transfection activity, the BSA of different isoelectric point value (pI) had a distinct influence on the CS-SA/BSA/DNA complexes. CS-SA/BSA(4.7)/DNA and CS-SA/BSA(6.0)/DNA complexes had better transfection efficiency than binary complexes, especially CS-SA/BSA(4.7)/DNA complexes which showed the highest transfection efficiency. On the contrary, CS-SA/BSA(9.3)/DNA complexes had undesirable performances. Interestingly, the incorporation of BSA(4.7) in CS-SA/DNA complexes significantly enhanced the dissociation of polymer/DNA complexes and improved the release of DNA intracellular without influencing their cellular uptake. The aforementioned results indicated that the acid group in protein played an important role in enhancing the transfection efficiency of CS/BSA/DNA complexes, and the study provided guidelines in the design of an efficient vector for DNA transfection.

Hyaluronic acid reagent functional chitosan-PEI conjugate with AQP2-siRNA suppressed endometriotic lesion formation

“…10,11 In addition, we also demonstrated the feasibility of endometriosis treatment by using chitosan-derived micelles/pigment epithelium-derived factor gene delivery system. 12 However, the efficiency of transfection is not satisfactory with this kind of gene delivery.…”

The effect of dual-functional hyaluronic acid-vitamin E succinate micelles on targeting delivery of doxorubicin

“…38,39 Moreover, even when the concentration of FBS reached 10%, the size of the micelles increased 1.5-fold of the original size after 24-hour incubation, but no visible precipitation of micelles was observed. Due to the slight negative charge of FBS, 40 the zeta potentials of HA-VES12/DOX decreased with an increase in FBS concentrations, which could further reduce the adsorption of FBS on the surface of HA-VES micelles by means of charge repulsion and maintain micellar structure integrity in the blood circulation.…”

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

“…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.…”