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Tetrahedral framework nucleic acid-Based Delivery of Resveratrol Alleviates Insulin Resistance:From Innate to Adaptive Immunity

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Nano-Micro Letters 2021年第6期13卷 1-16页

作者： Yanjing Li Shaojingya Gao Sirong Shi Dexuan Xiao Shuanglin Peng Yang Gao Ying Zhu Yunfeng Lin State Key Laboratory of Oral Diseases West China Hospital of StomatologySichuan UniversityChengdu 610041P.R.China Department of Oral and Maxillofacial Surgery Hospital of StomatologySouthwest Medical UniversityLuzhou 646000P.R.China Zhangjiang Laboratory Shanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210P.R.China CAS Key Laboratory of Interfacial Physics and Technology Division of Physical BiologyShanghai Institute of Applied PhysicsShanghai Synchrotron Radiation FacilityChinese Academy of SciencesShanghai 201800P.R.China College of Biomedical Engineering Sichuan UniversityChengdu 610041P.R.China

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.

关键词： Tetrahedral framework nucleic acid Resveratrol Insulin resistance Inflammation Innate immunity Adaptive immunity

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Tetrahedral framework nucleic acids-based delivery of microRNA-155 inhibits choroidal neovascularization by regulating the polarization of macrophages

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Bioactive Materials 2022年第8期7卷 134-144页

作者： Xin Qin Lirong Xiao Ni Li Chen Hou Wenman Li Jiajie Li Naihong Yan Yunfeng Lin State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu610041China Research Laboratory of Ophthalmology West China HospitalSichuan UniversityChengdu610041China College of Biomedical Engineering Sichuan UniversityChengdu610041China

Choroidal neovascularization(CNV)is a common pathological feature of various eye diseases and an important cause of visual impairment in middle-aged and elderly patients.In previous studies,Tetrahedral framework nucleic acids(tFNAs)showed good carrier performance.In this experiment,we developed microRNA-155-equipped tFNAs(T-155)and explored its biological effects on CNV.Based on the results of in-vitro experiments,T-155 could regulate macrophages into the antiangiogenic M1 type.Then,we injected T-155 into the vitreous of laser-induced CNV model mice and found that T-155 significantly reduced the size and area of CNV,inhibited blood vessel leakage.In summary,we prove that T-155 could regulate the inflammatory process of CNV by polarizing macrophages,thereby improving the symptoms of CNV.Thus,T-155 might become a new DNA-based drug with great potential for treating CNV.

关键词： Choroidal neovascularization Tetrahedral framework nucleic acid Macrophages MicroRNA-155 Immunity therapy

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Tetrahedral framework nucleic acids regulate osteogenic differentiation potential of osteoporotic adipose-derived stem cells

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Chinese Chemical Letters 2022年第5期33卷 2517-2521页

作者： Tianyu Chen Dexuan Xiao Yanjing Li Sirong Shi Xiao Yang Shuanglin Peng Bin Guo Xiaoxiao Cai State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China Department of Stomatology First Medical Center of Chinese PLA General HospitalBeijing 100853China

Osteoporosis(OP)is a noncommunicable bone disease caused by a shift in the balance between os-teoblasts and osteoclasts,and can severely affect the health of elderly persons.Autologous stem-cell transplantation can improve reduced bone density and weakened fracture healing abilities in patients with OP.However,OP can adversely affect the osteogenesis and proliferation abilities of autologous adipose-derived stem cells(ASCs).Therefore,an effective drug is required to facilitate autologous ASCs to recover their osteogenic and proliferative potential.Tetrahedral framework nucleic acid(tFNA)is a new type of nanomaterial that has ability to regulate the biological behavior of cells effectively and en-hance the bioactivity of stem cells.In this study,we examine the effects of tFNAs on the osteogenic differentiation and proliferation abilities of ASCs in rats with OP.The results indicate that the 250 nmol/L tFNAs can considerably increase the expression of osteogenesis-related markers,effectively promote the proliferation and osteogenic differentiation of osteoporotic ASCs(OP-ASCs),and help them to regain their osteogenic and proliferative potential.In short,tFNAs can enable OP-ACSs to recover their osteogenic po-tential and promote their proliferation and,therefore,can play a key regulatory role in autologous ASC transplantation.

关键词： Osteoporosis Tetrahedral framework nucleic acid Adipose-derived stem cell Autologous stem-cell transplantation Osteogenic differentiation

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