Reduction-responsive multifunctional hyperbranched polyaminoglycosides with excellent antibacterial activity, biocompatibility and gene transfection capability

Yajun Huang; Xiaokang Ding; Yu Qi; Bingran Yu; Fu-Jian Xu

doi:10.1016/j.biomaterials.2016.08.025

Reduction-responsive multifunctional hyperbranched polyaminoglycosides with excellent antibacterial activity, biocompatibility and gene transfection capability

Biomaterials. 2016 Nov:106:134-43. doi: 10.1016/j.biomaterials.2016.08.025. Epub 2016 Aug 17.

Authors

Yajun Huang¹, Xiaokang Ding¹, Yu Qi¹, Bingran Yu², Fu-Jian Xu³

Affiliations

¹ State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China; Key Laboratory of Carbon Fiber and Functional Polymers, Beijing University of Chemical Technology, Ministry of Education, Beijing 100029, China; Beijing Laboratory of Biomedical Materials, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China.
² State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China; Key Laboratory of Carbon Fiber and Functional Polymers, Beijing University of Chemical Technology, Ministry of Education, Beijing 100029, China; Beijing Laboratory of Biomedical Materials, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China. Electronic address: yubr@mail.buct.edu.cn.
³ State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China; Key Laboratory of Carbon Fiber and Functional Polymers, Beijing University of Chemical Technology, Ministry of Education, Beijing 100029, China; Beijing Laboratory of Biomedical Materials, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, China. Electronic address: xufj@mail.buct.edu.cn.

PMID: 27561884
DOI: 10.1016/j.biomaterials.2016.08.025

Abstract

There is an increasing demand in developing of multifunctional materials with good antibacterial activity, biocompatibility and drug/gene delivery capability for next-generation biomedical applications. To achieve this purpose, in this work series of hydroxyl-rich hyperbranched polyaminoglycosides of gentamicin, tobramycin, and neomycin (HP and SS-HP with redox-responsive disulfide bonds) were readily synthesized via ring-opening reactions in a one-pot manner. Both HP and SS-HP exhibit high antibacterial activity toward Escherichia coli and Staphylococcus aureus. Meanwhile, the hemolysis assay of the above materials shows good biocompatibility. Moreover, SS-HPs show excellent gene transfection efficiency in vitro due to the breakdown of reduction-responsive disulfide bonds. For an in vivo anti-tumor assay, the SS-HP/p53 complexes exhibit potent inhibition capability to the growth of tumors. This study provides a promising approach for the design of next-generation multifunctional biomedical materials.

Keywords: Aminoglycoside; Antibacterial; Gene vectors; Hyperbranched polymer; Reduction-responsive.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aminoglycosides / administration & dosage*
Aminoglycosides / chemistry
Animals
Anti-Bacterial Agents / administration & dosage*
Anti-Bacterial Agents / chemistry
Bacterial Physiological Phenomena / drug effects*
Biocompatible Materials / administration & dosage
Biocompatible Materials / chemistry
Cell Line, Tumor
Cell Survival / drug effects
Female
HEK293 Cells
Humans
Materials Testing
Mice
Mice, Inbred C57BL
Mice, Nude
Nanocapsules / administration & dosage*
Nanocapsules / chemistry
Neoplasms, Experimental / drug therapy*
Neoplasms, Experimental / pathology
Oxidation-Reduction
Plasmids / administration & dosage*
Transfection / methods*

Substances

Aminoglycosides
Anti-Bacterial Agents
Biocompatible Materials
Nanocapsules