Dextran-Peptide Hybrid for Efficient Gene Delivery
cationic lipids; cells; Chemistry; cytotoxicity; drug delivery; in-vitro; Materials Science; nanoparticles; nonviral vector; plasmid dna; polyethylenimine; therapy
Gene therapy has drawn significant interest in the past two decades since it provides a promising strategy to treat both genetic disorders and acquired diseases. However, the transfer of gene therapy to clinical applications is troubled with many difficulties, since many current systems are of toxicity, low transfection efficiency and low biodegradability. To address these challenges, we developed a dextran-peptide hybrid system as a safe and efficient vector for gene therapy and investigated the structure-function-cytotoxicity relationship of this dextran-peptide hybrid system. Dextrans (Dex10, Dex20, and Dex70) with different molecular weights (10, 20 and 70 kDa) were conjugated with a cationic peptide, R5H5, at various degrees of substitution. Gene expression and cytotoxicity mediated by this delivery system were evaluated against SKOV-3 human ovarian carcinoma cells and compared to 25 kDa branched poly(ethylenimine) (PEI). The results showed that Dex10-R5H5 and Dex20-R5H5 hybrids derived from low molecular weight dextrans induced higher gene expression and lower cytotoxicity than Dex70-R5H5 hybrid from higher molecular weight dextran. The best performance on gene expression was achieved by Dex10-R5H5 at 40% substitution of R5H5, which induced greater gene expression than PEI at a low N/P ratio of S. Dex10-R5H5/DNA complexes at 40% substitution of R5H5 also showed much higher cell viability (93%) than PEI/DNA (66%) at the same N/P ratio. These results indicate that the Dex-R5H5 hybrid with the low molecular weight of dextran and the high degree of substitution of R5H5 is a very promising material for safe and efficient gene therapy.
Tang Q; Cao B; Lei X; Sun B B; Zhang Y Q; Cheng G
Langmuir
2014
2014-05
Journal Article
<a href="http://doi.org/10.1021/la500905z" target="_blank" rel="noreferrer noopener">10.1021/la500905z</a>
Cholesterol-Peptide Hybrids to Form Liposome-Like Vesicles for Gene Delivery
condensation; dna; histidine; nanoparticles; oligopeptides; polymers; prospects; Science & Technology - Other Topics; systems; therapy; vectors
In this paper, four amphiphilic cholesterol-peptide conjugates (Ch-R5H5, Ch-R3H3, Ch-R5 and Ch-R5) were designed and synthesized, and their properties in gene delivery were evaluated in vitro with an aim of developing more efficient gene delivery carriers. These amphiphilic cholesterol-peptide conjugates are composed of hydrophobic cholesterol and positively charged peptides. They were able to self-assemble into micelles at low concentrations and their critical micelle concentrations in phosphate buffered saline (pH 7.4) are <= 85 mu g/mL. Amphiphilic cholesterol-peptide conjugates condensed DNA more efficiently than a hydrophilic cationic oligoarginine (R10) peptide with no hydrophobic segment. Their transfection efficiencies were at least two orders of magnitude greater than that of R10 peptide in HEK-293 cells. Moreover, the introduction of histidine residues in cholesterol-peptide conjugates led to higher gene expression efficiency compared with cholesterol-peptides without histidine (Ch-R5 and Ch-R3), and the luciferase expression level was comparable or even higher than that induced by PEI at its optimal N/P ratio. In particular, Ch-R5H5 condensed DNA into smaller nanoparticles than Ch-R3H3 at higher N/P ratios, and the minimum size of Ch-R5H5/DNA complexes was 180 nm with zeta potential of 23 mV, achieved at the N/P ratio of 30. This liposome-like vesicle may be a promising gene delivery carrier for intravenous therapy.
Tang Q; Cao B; Wu H Y; Cheng G
PLOS ONE
2013
2013-01
Journal Article
<a href="http://doi.org/10.1371/journal.pone.0054460" target="_blank" rel="noreferrer noopener">10.1371/journal.pone.0054460</a>
A naturally derived dextran-peptide vector for microRNA antagomir delivery
cells; Chemistry; gene delivery; human cancers; in-vitro; mechanism; RNA interference; therapy; vivo
Single stranded microRNAs and their antagomirs are unstable and polyanionic, which impedes efficient cellular uptake and reduces half-life. Therefore, effective delivery systems with low toxicity for microRNAs are urgently needed for the success of microRNA-based therapy. Here, a dextran-peptide hybrid, Dex10-R5H5(40%), was developed as a carrier to deliver microRNAs. Dex10-R5H5(40%) loaded with antagomir-149 could reduce the level of endogenous microRNA-149 by 76% and it is more effective than the commercially available transfection reagent, RNAiMAX, which leads to 67% reduction. Additionally, Dex10-R5H5(40%) exhibited no cytotoxicity to HepG2 cells. These results indicate that the dextran-peptide hybrid may be a promising delivery system for the safe and efficient microRNA-based therapy.
Tang Q; Lei X; Cao B; Sun B B; Zhang Y Q; Cheng G
Rsc Advances
2015
2015
Journal Article
<a href="http://doi.org/10.1039/c4ra12878h" target="_blank" rel="noreferrer noopener">10.1039/c4ra12878h</a>