Tetrahedral Framework Nucleic Acid-Based Delivery of Resveratrol Alleviates Insulin Resistance:From Innate to Adaptive Immunity

作     者：Yanjing Li Shaojingya Gao Sirong Shi Dexuan Xiao Shuanglin Peng Yang Gao Ying Zhu Yunfeng Lin Yanjing Li;Shaojingya Gao;Sirong Shi;Dexuan Xiao;Shuanglin Peng;Yang Gao;Ying Zhu;Yunfeng Lin

作者机构：State Key Laboratory of Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041P.R.China Department of Oral and Maxillofacial SurgeryHospital of StomatologySouthwest Medical UniversityLuzhou 646000P.R.China Zhangjiang LaboratoryShanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210P.R.China CAS Key Laboratory of Interfacial Physics and TechnologyDivision of Physical BiologyShanghai Institute of Applied PhysicsShanghai Synchrotron Radiation FacilityChinese Academy of SciencesShanghai 201800P.R.China College of Biomedical EngineeringSichuan UniversityChengdu 610041P.R.China 

出 版 物：《Nano-Micro Letters》 (纳微快报（英文版）)

年 卷 期：2021年第13卷第6期

页      面：1-16页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 0808[工学-电气工程] 0809[工学-电子科学与技术（可授工学、理学学位）] 0817[工学-化学工程与技术] 0805[工学-材料科学与工程（可授工学、理学学位）] 10[医学] 0702[理学-物理学] 

基　　金：National Key R&D Program of China(2019YFA0110600) National Natural Science Foundation of China(81970916,81671031) the LU JIAXI International team program supported by the K.C.Wong Education Foundation and CAS and the Youth Innovation Promotion Association of CAS(Grant No.2016236). 

主　　题：Tetrahedral framework nucleic acid Resveratrol Insulin resistance Inflammation Innate immunity Adaptive immunity 

摘      要：Obesity-induced insulin resistance is the hallmark of metabolic syndrome,and chronic,low-grade tissue inflammation links obesity to insulin resistance through the activation of tissue-infiltrating immune cells.Current therapeutic approaches lack efficacy and immunomodulatory capacity.Thus,a new therapeutic approach is needed to prevent chronic inflammation and alleviate insulin resistance.Here,we synthesized a tetrahedral framework nucleic acid(tFNA)nanoparticle that carried resveratrol(RSV)to inhibit tissue inflammation and improve insulin sensitivity in obese mice.The prepared nanoparticles,namely tFNAs-RSV,possessed the characteristics of simple synthesis,stable properties,good water solubility,and superior biocompatibility.The tFNA-based delivery ameliorated the lability of RSV and enhanced its therapeutic efficacy.In high-fat diet(HFD)-fed mice,the administration of tFNAs-RSV ameliorated insulin resistance by alleviating inflammation status.tFNAs-RSV could reverse M1 phenotype macrophages in tissues to M2 phenotype macrophages.As for adaptive immunity,the prepared nanoparticles could repress the activation of Th1 and Th17 and promote Th2 and Treg,leading to the alleviation of insulin resistance.Furthermore,this study is the first to demonstrate that tFNAs,a nucleic acid material,possess immunomodulatory capacity.Collectively,our findings demonstrate that tFNAs-RSV alleviate insulin resistance and ameliorate inflammation in HFD mice,suggesting that nucleic acid materials or nucleic acid-based delivery systems may be a potential agent for the treatment of insulin resistance and obesity-related metabolic diseases.