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Nano Research

Article Title

Surface charge tunable nanoparticles for TNF-α siRNA oral delivery for treating ulcerative colitis

Authors

Shoaib Iqbal, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
Xiaojiao Du, School of Medicine, South China University of Technology, Guangzhou 510006, China Institutes for Life Sciences, South China University of Technology, Guangzhou 510006, China Key Laboratory of Biomedical Materials of Ministry of Education, South China University of Technology, Guangzhou 510641, China National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China
Jilong Wang, School of Life Sciences, University of Science and Technology of China, Hefei 230027, China
Hongjun Li, School of Medicine, South China University of Technology, Guangzhou 510006, China Institutes for Life Sciences, South China University of Technology, Guangzhou 510006, China
Youyong Yuan, School of Medicine, South China University of Technology, Guangzhou 510006, China Institutes for Life Sciences, South China University of Technology, Guangzhou 510006, China National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China
Jun Wang, School of Medicine, South China University of Technology, Guangzhou 510006, China Institutes for Life Sciences, South China University of Technology, Guangzhou 510006, China Key Laboratory of Biomedical Materials of Ministry of Education, South China University of Technology, Guangzhou 510641, China National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China Research Institute for Food Nutrition and Human Health, Guangzhou 510641, China

Keywords

surface charge, TNF-α siRNA, drug delivery, polymeric nanoparticles, ulcerative colitis

Abstract

ABSTRACT Nanoparticle (NP) drug delivery systems have been successfully designed and implemented to orally deliver siRNAs for inflammatory disorders. However, the influence of surface charge on orally administered siRNA nanocarriers has not been investigated. In this study, we prepared structurally related poly(ethylene glycol)-block-poly(lactic-co-glycolic acid) (PEG5K-b-PLGA10K) NPs with the assistance of a synthesized lipid featuring surface amine groups for subsequent charge tuning. NPs were prepared by a double emulsion method, and their surface charge could be tuned and controlled by a succinylation reaction to yield NPs with different surface charges, while maintaining their size and composition. The prepared NPs were termed as aminated NPs (ANPs), plain NPs (PNPs), or carboxylated NPs (CNPs) based on their surface charge. All NPs exhibited the desired structural stability and siRNA integrity after enzymatic degradation. In vivo studies showed that ANPs significantly accumulated in inflamed colons, and they were successful in decreasing TNF- secretion and mRNA expression levels while maintaining colonic histology in a murine model of acute ulcerative colitis (UC). This study described a methodology to modify the surface charge of siRNA-encapsulating polymeric NPs and highlighted the influence of surface charge on oral delivery of siRNA for localized inflammatory disorders.

Graphical Abstract

Publisher

Tsinghua University Press

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