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Transferrin-functionalized chitosan-graft-poly(L-lysine) dendrons as a high-efficiency gene delivery carrier for nasopharyngeal carcinoma therapy

Abstract

A transferrin-targeting chitosan-graft-poly(L-lysine) dendrons (CS-PLLD-Tf) was synthesized in this work and then used to deliver MMP-9 shRNA plasmid to HNE-1 cells for gene therapy. The obtained CS-PLLD-Tf displayed excellent gene transfection in vitro, verifying the strategy of constructing a high-efficiency gene carrier by conjugating the multiple low generation PLLDs to one molecule of CS to form a copolymer. Particularly, CS-PLLD-Tf showed much higher gene transfection efficiency than that of PEI-25k and CS-PLLD in the presence of serum, and more than 40% HNE-1 cells were transfected. This result led to an obvious decrease in MMP-9 protein expression and the apoptosis of HNE-1 cells as well as inhibition the growth and invasion of HNE-1 tumors. The in vivo anti-tumor assay showed that CS-PLLD-Tf delivered MMP-9 plasmid effectively and the tumor volume decreased more than 77% compared with PBS control group. Moreover, CS-PLLD-Tf displayed a higher bioavailability and good biocompatibility such as lower cytotoxicity, excellent blood compatibility and non-toxicity to organs, suggesting a potential application in gene therapy to tumors.

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Publication details

The article was received on 21 Feb 2018, accepted on 02 Jun 2018 and first published on 09 Jun 2018


Article type: Paper
DOI: 10.1039/C8TB00489G
Citation: J. Mater. Chem. B, 2018, Accepted Manuscript
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    Transferrin-functionalized chitosan-graft-poly(L-lysine) dendrons as a high-efficiency gene delivery carrier for nasopharyngeal carcinoma therapy

    T. Liu, S. Chen, S. Zhang, X. Wu, P. Wu, B. Miao and X. Cai, J. Mater. Chem. B, 2018, Accepted Manuscript , DOI: 10.1039/C8TB00489G

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