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

作　　者：Shoaib Iqbal Xiaojiao Du Jilong Wang Hongjun Li Youyong Yuan Jun Wang 

机构地区：[1]School of Life Sciences, University of Science and Technology of China, Hefei 230027, China [2]School of Medicine, South China University of Technology, Guangzhou 510006, China [3]Institutes for Life Sciences, South China University of Technology, Guangzhou 510006, China [4]Key Laboratory of Biomedical Materials of Ministry of Education, South China University of Technology, Guangzhou 510641, Chino [5]National Engineering Research Center for Tissue Restoration and Reconstruction, Guangzhou 510006, China [6]Research Institute for Food Nutrition and Human Health, Guangzhou 510641, China

出　　处：《Nano Research》2018年第5期2872-2884,共13页纳米研究（英文版）

基　　金：This work was supported by the National Basic Research Program of China （No. 2015CB932100）, the National Natural Science Foundation of China （Nos. 51503195, 51390482 and 51633008）, the National Key R＆D Program of China （No. 2017YFA0205600）, the Fundamental Research Funds for the Central Universities, and 111 Project （No. B17018）. S. I. is also grateful for the CAS-TWAS president fellowship.

摘　　要：Nanopartide （NP） drug delivery systems have been successfully designed and implemented to orally deliver small interfering RNAs （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-α 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.Nanopartide （NP） drug delivery systems have been successfully designed and implemented to orally deliver small interfering RNAs （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-α 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.

关 键 词：surface charge tumor necrosis factor alpha（TNF-α） small interferingRNA （siRNA） drug delivery polymeric nanoparticles ulcerative colitis 

分 类 号：S858.28[农业科学—临床兽医学] Q522[农业科学—兽医学]