期刊
BIOMACROMOLECULES
卷 14, 期 2, 页码 485-494出版社
AMER CHEMICAL SOC
DOI: 10.1021/bm301720g
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资金
- Fraternal Order of Eagles
- NDEPSCoR
- Directorate For Engineering
- Div Of Chem, Bioeng, Env, & Transp Sys [0959422] Funding Source: National Science Foundation
- Office Of The Director
- EPSCoR [0814442] Funding Source: National Science Foundation
To develop a safe, effective, and biocompatible gene delivery vector, a series of hydrophobic amino acid grafted chitosan (AGC) derivatives were synthesized by carbodiimide mediated coupling reaction. Chemical characterization of AGC polymers was performed by NMR and elemental analysis. AGC polymers demonstrated excellent blood compatibility and cell viability, as evaluated by hemolysis and MTT assay, respectively. AGC polymers could effectively bind and condense plasmid DNA (pDNA) to form polyplexes in the size range of 161-263 nm and possessed net cationic charge. The resultant polyplex showed 3.4-5.4-fold greater cellular uptake and 13-30-fold higher transfection efficiency in HEK 293 cells as compared to unmodified chitosan. Moreover, both cellular uptake and transfection efficiency improved with the increasing amino acid hydrophobicity. Hydrophobic amino acid substitution contributed to the enhance pDNA release at cytosolic pH. These data demonstrate AGC polymers as a promising novel nonviral gene delivery vector.
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