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Prospects and challenges of dynamic DNA nanostructures in biomedical applications

Bone Research 2022年第3期10卷 454-468页

作者： Taoran Tian Yanjing Li yunfeng lin State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041P.R.China Department of Prosthodontics Tianjin Medical University School and Hospital of StomatologyTianjin 300070P.R.China

The physicochemical nature of DNA allows the assembly of highly predictable structures via several fabrication strategies, which have been applied to make breakthroughs in various fields. Moreover, DNA nanostructures are regarded as materials with excellent editability and biocompatibility for biomedical applications. The ongoing maintenance and release of new DNA structure design tools ease the work and make large and arbitrary DNA structures feasible for different applications. However, the nature of DNA nanostructures endows them with several stimulus-responsive mechanisms capable of responding to biomolecules, such as nucleic acids and proteins, as well as biophysical environmental parameters, such as temperature and p H. Via these mechanisms, stimulus-responsive dynamic DNA nanostructures have been applied in several biomedical settings, including basic research, active drug delivery, biosensor development, and tissue engineering. These applications have shown the versatility of dynamic DNA nanostructures, with unignorable merits that exceed those of their traditional counterparts, such as polymers and metal ***, there are stability, yield, exogenous DNA, and ethical considerations regarding their clinical translation. In this review, we first introduce the recent efforts and discoveries in DNA nanotechnology, highlighting the uses of dynamic DNA nanostructures in biomedical applications. Then, several dynamic DNA nanostructures are presented, and their typical biomedical applications,including their use as DNA aptamers, ion concentration/p H-sensitive DNA molecules, DNA nanostructures capable of strand displacement reactions, and protein-based dynamic DNA nanostructures, are discussed. Finally, the challenges regarding the biomedical applications of dynamic DNA nanostructures are discussed.

关键词： particles dynamic breakthrough

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Osteogenesis of Adipose-Derived Stem Cells

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Bone Research 2013年第2期1卷 133-145页

作者： Brian E. Grottkau yunfeng lin Department of Orthopaedic Surgery MassGeneral Hospital for Children and the Pediatric Orthopaedic Laboratory for Tissue Engineering and Regenerative MedicineHarvard Medical SchoolBostonMassachusettsUSA

Current treatment options for skeletal repair, including immobilization, rigid fixation, alloplastic materials and bone grafts, have significant limitations. Bone tissue engineering offers a promising method for the repair of bone deficieny caused by fractures, bone loss and tumors. The use of adipose derived stem cells （ASCs） has received attention because of the self-renewal ability, high proliferative capacity and potential of osteogenic differentiation in vitro and in vivo studies of bone regeneration. Although cell therapies using ASCs are widely promising in various clinical fields, no large human clinical trials exist for bone tissue engineering. The aim of this review is to introduce how they are harvested, examine the characterization of ASCs, to review the mechanisms of osteogenic differentiation, to analyze the effect of mechanical and chemical stimuli on ASC osteodifferentiation, to summarize the current knowledge about usage of ASC in vivo studies and clinical trials, and finally to conclude with a general summary of the field and comments on its future direction.

关键词： adipose derived stem cells osteogenesis bone tissue engineering osteogenic differentiation

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Nanomaterials and bone regeneration

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Bone Research 2015年第3期3卷 123-129页

作者： Tao Gong Jing Xie Jinfeng Liao Tao Zhang Shiyu lin yunfeng lin State Key Laboratory of Oral Diseases West China Hospital of Stomatology Sichuan University

The worldwide incidence of bone disorders and conditions has been increasing. Bone is a nanomaterials composed of organic （mainly collagen） and inorganic （mainly nano-hydroxyapatite） components, with a hierarchical structure ranging from nanoscale to macroscale. In consideration of the serious limitation in traditional therapies, nanomaterials provide some new strategy in bone regeneration. Nanostructured scaffolds provide a closer structural support approximation to native bone architecture for the cells and regulate cell proliferation, differentiation, and migration, which results in the formation of functional tissues. In this article, we focused on reviewing the classification and design of nanostructured materials and nanocarrier materials for bone regeneration, their cell interaction properties, and their application in bone tissue engineering and regeneration. Furthermore, some new challenges about the future research on the application of nanomaterials for bone regeneration are described in the conclusion and perspectives part.

关键词： bone ECM

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Tetrahedral framework nucleic acids promote cognitive impairment recovery post traumatic brain injury

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Chinese Chemical Letters 2023年第4期34卷 141-147页

作者： Yangyang Wang Weiqiang Jia Jianwei Zhu Ruxiang Xu yunfeng lin Department of Neurosurgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 611731China Department of Neurosurgery The First People’s Hospital in Shuangliu District/West China Airport HospitalSichuan UniversityChengdu 610299China State Key Laboratory of Oral Diseases National Clinical Research Center for Oral Disease West China Hospital of StomatologySichuan UniversityChengdu 610041China

Cognitive impairment often occurs after post traumatic brain injury. In addition, recovery of cognitive impairment is largely dependent on spontaneous repair and the severity of secondary insult. The tetrahedral framework nucleic acid is a novel nanostructure has been shown to have a positive biological effect in promoting regeneration and anti-inflammation. To explore the treatment effect of tetrahedral framework nucleic acids for cognitive impairment recovery post traumatic brain injury, we established a mouse model of traumatic brain injury and verified the efficacy of tetrahedral framework nucleic acids in promoting cognitive impairment recovery post traumatic brain injury. The results show that the tetrahedral framework nucleic acids promoted the recovery of post-traumatic cognitive function by enhancing the proliferation of endogenous neural stem cells. Besides, tetrahedral framework nucleic acids modulated the neuroinflammatory response in the acute phase by inhibiting excessive astrocyte and microglial activation. Taken together, the results of the study indicate tetrahedral framework nucleic acids for treatment of cognitive impairment post traumatic brain injury.

关键词： Tetrahedral framework nucleic acids Traumatic brain injury Cognitive impairment Neural stem cell Neuroinflammation

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Tetrahedral framework nucleic acids promote the proliferation and differentiation potential of diabetic bone marrow mesenchymal stem cell

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Chinese Chemical Letters 2024年第9期35卷 284-288页

作者： Yanjing Li Jiayin Li Yuqi Chang yunfeng lin Lei Sui Department of Prosthodontics Tianjin Medical University School and Hospital of StomatologyTianjin 300070China State Key Laboratory of Oral Diseases West China Hospital of StomatologySichuan UniversityChengdu 610041China

Diabetes mellitus considerably affects bone marrow mesenchymal stem cells(BMSCs),for example,by inhibiting their proliferation and differentiation potential,which enhances the difficulty in endogenous bone ***,effective strategies for enhancing the functions of BMSCs in diabetes have farreaching consequences for bone healing and regeneration in diabetes *** framework nucleic acids(tFNAs)are nucleic acid nanomaterials that can autonomously enter cells and regulate their *** this study,we evaluated the effects of tFNAs on BMSCs from diabetic *** found that tFNAs could promote the proliferation,migration,and osteogenic differentiation of BMSCs from rats with type 2 diabetes mellitus,and inhibited cell senescence and ***,tFNAs effectively scavenged the accumulated reactive oxygen species and activated the suppressed protein kinase B(Akt)signaling ***,we show that tFNAs can recover the proliferation and osteogenic potential of diabetic BMSCs by alleviating oxidative stress and activating Akt *** study provides a strategy for endogenous bone regeneration in diabetes and also paves the way for exploiting DNA-based nanomaterials in regenerative medicine.

关键词： Bone marrow mesenchymal stem cell Diabetes mellitus DNA-based nanomaterial Tetrahedral framework nucleic acids Endogenous bone regeneration

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Multi?targeted Antisense Oligonucleotide Delivery by a Framework Nucleic Acid for Inhibiting Biofilm Formation and Virulence

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Nano-Micro Letters 2020年第6期12卷 113-125页

作者： Yuxin Zhang Xueping Xie Wenjuan Ma Yuxi Zhan Chenchen Mao Xiaoru Shao yunfeng lin State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041People’s Republic of China

Biofilm formation is responsible for numerous chronic infections and represents a serious health *** and the extracellular polysaccharides(EPS)cause biofilms to become adherent,toxic,resistant to antibiotics,and ultimately difficult to *** of EPS synthesis can prevent the formation of bacterial biofilms,reduce their robustness,and promote ***,we have developed a framework nucleic acid delivery system with a tetrahedral *** can easily access bacterial cells and functions by delivering antisense oligonucleotides that target specific *** designed antisense oligonucleotide sequences with multiple targets based on conserved regions of the VicK protein-binding *** delivered to bacterial cells,they significantly decreased EPS synthesis and biofilm *** to existing approaches,this system is highly efficacious because it simultaneously reduces the expression of all targeted genes(gtfBCD,gbpB,ftf).We demonstrate a novel nucleic acid-based nanomaterial with multi-targeted inhibition that has great potential for the treatment of chronic infections caused by biofilms.

关键词： Biofilm Framework nucleic acid Multi-targeting Antisense oligonucleotide Delivery system

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The biological applications of DNA nanomaterials:current challenges and future directions

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Signal Transduction and Targeted Therapy 2021年第11期6卷 3202-3229页

作者： Wenjuan Ma Yuxi Zhan Yuxin Zhang Chenchen Mao Xueping Xie yunfeng lin State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengduPeople’s Republic of China College of Biomedical Engineering Sichuan UniversityChengduPeople’s Republic of China

DNA,a genetic material,has been employed in different scientific directions for various biological applications as driven by DNA nanotechnology in the past decades,including tissue regeneration,disease prevention,inflammation inhibition,bioimaging,biosensing,diagnosis,antitumor drug delivery,and *** the rapid progress in DNA nanotechnology,multitudinous DNA nanomaterials have been designed with different shape and size based on the classic Watson–Crick base-pairing for molecular *** DNA materials could functionally change cell biological behaviors,such as cell migration,cell proliferation,cell differentiation,autophagy,and anti-inflammatory *** single-stranded DNAs(ssDNAs)or RNAs with secondary structures via self-pairing,named aptamer,possess the ability of targeting,which are selected by systematic evolution of ligands by exponential enrichment(SELEX)and applied for tumor targeted diagnosis and *** DNA nanomaterials with three-dimensional(3D)nanostructures and stable structures are investigated as drug carrier systems to delivery multiple antitumor medicine or gene therapeutic *** the functional DNA nanostructures have promoted the development of the DNA nanotechnology with innovative designs and preparation strategies,and also proved with great potential in the biological and medical use,there is still a long way to go for the eventual application of DNA materials in real *** in this review,we conducted a comprehensive survey of the structural development history of various DNA nanomaterials,introduced the principles of different DNA nanomaterials,summarized their biological applications in different fields,and discussed the current challenges and further directions that could help to achieve their applications in the future.

关键词： diagnosis prevention pairing

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A DNA tetrahedron-based ferroptosis-suppressing nanoparticle: superior delivery of curcumin and alleviation of diabetic osteoporosis

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Bone Research 2024年第1期12卷 227-239页

作者： Yong Li Zhengwen Cai Wenjuan Ma Long Bai En Luo yunfeng lin State Key Laboratory of Oral Diseases&National Center for Stomatology&National Clinical Research Center for Oral Diseases West China Hospital of StomatologySichuan UniversityChengduSichuan 610041PR China Department of Oral and Maxillofacial Surgery Affiliated Stomatological HospitalSouthwest Medical UniversityLuzhouSichuan 646000PR China Sichuan Provincial Engineering Research Center of Oral Biomaterials ChengduSichuan 610041China

Diabetic osteoporosis(DOP)is a significant complication that poses continuous threat to the bone health of patients with diabetes;however,currently,there are no effective treatment *** patients with diabetes,the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells(BMSCs),leading to significant skeletal *** address this issue,we aimed to target ferroptosis and propose a novel therapeutic approach for the treatment of *** synthesized ferroptosis-suppressing nanoparticles,which could deliver curcumin,a natural compound,to the bone marrow using tetrahedral framework nucleic acid(tFNA).This delivery system demonstrated excellent curcumin bioavailability and stability,as well as synergistic properties with *** in vitro and in vivo experiments revealed that nanoparticles could enhance mitochondrial function by activating the nuclear factor E2-related factor 2(NRF2)/glutathione peroxidase 4(GPX4)pathway,inhibiting ferroptosis,promoting the osteogenic differentiation of BMSCs in the diabetic microenvironment,reducing trabecular loss,and increasing bone *** findings suggest that curcumin-containing DNA tetrahedron-based ferroptosissuppressing nanoparticles have a promising potential for the treatment of DOP and other ferroptosis-related diseases.

关键词： curcumin osteoporosis diabetic

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A tetrahedral framework nucleic acid based multifunctional nanocapsule for tumor prophylactic mRNA vaccination

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Chinese Chemical Letters 2023年第7期34卷 169-175页

作者： Yuhao Liu Songhang Li Shiyu lin Sirong Shi Taoran Tian Bowen Zhang Tao Zhang yunfeng lin State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan University Chengdu 610041China Key Laboratory of Oral Biomedical Research of Zhejiang Province Zhejiang UniversityHangzhou 31000China Guanghua School of Stomatology Guangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhou 510055China

Synthetic antigen-encoding mRNA plays an increasingly significant role in tumor vaccine technology owing to its antigen-specific immune-activation. However, its immune efficacy is challenged by inferior delivery efficiency and demand for suitable adjuvants. Here, we develop a novel mRNA nanovaccine based on a multifunctional nanocapsule, which is a dual-adjuvant formulation composed of cytosine-phosphateguanine motifs loaded tetrahedral framework nucleic acid(CpG-tFNA) and an immunopeptide murine β-defensin 2(mDF2β). This m RNA nanovaccine successfully achieves intracellular delivery, antigen expression and presentation of dendritic cells, and proliferation of antigen-specific T cells. In a tumor prophylactic vaccination model, it exerts an excellent inhibitory effect on lymphoma occurrence through cellular immunity. This mRNA nanovaccine has promising prophylactic applications in tumors and many other diseases.

关键词： Tetrahedral framework nucleic acid(tFNA) RNA nanovaccine Cytosine-phosphate-guanine(CpG)motifs Murineβ-defensin 2(mDF2β) Tumor immunotherapy

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Angiogenesis in a 3D model containing adipose tissue stem cells and endothelial cells is mediated by canonical Wnt signaling

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Bone Research 2017年第4期5卷 330-342页

作者： Xiaoxiao Cai Jing Xie Yang Yao Xiangzhu Cun Shiyu lin Taoran Tian Bofeng Zhu yunfeng lin State Key Laboratory of Oral Diseases National Clinical Research Center for Oral DiseasesWest China Hospital of StomatologySichuan UniversityChengdu 610041China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research College of StomatologyXi'an Jiaotong UniversityXi'an 710004China Clinical Research Center of Shaanxi Province for Dental and Maxillofacial Diseases College of StomatologyXi'an Jiaotong UniversityXi'an 710004China Department of Forensic Genetics School of Forensic MedicineSouthern Medical UniversityGuangzhou 510515China

Adipose-derived stromal cells （ASCs） have gained great attention in regenerative medicine. Progress in our understanding of adult neovascularization further suggests the potential of ASCs in promoting vascular regeneration, although the specific cues that stimulate their angiogenic behavior remain controversial In this study, we established a three-dimensional （3D） angiogenesis model by co-culturing ASCs and endothelial cells （ECs） in collagen gel and found that ASC-EC-instructed angiogenesis was regulated by the canonical Wnt pathway. Furthermore, the angiogenesis that occurred in implants collected after injections of our collagen gel- based 3D angiogenesis model into nude mice was confirmed to be functional and also regulated by the canonical Wnt pathway. Wnt regulation of angiogenesis involving changes in vessel length, vessel density, vessel sprout, and connection numbers occurred in our system. Wnt signaling was then shown to regulate ASC- mediated paracrine signaling during angiogenesis through the nuclear translocation of β-catenin after its cytoplasmic accumulation in both ASCs and ECs. This translocation enhanced the expression of nuclear cofactor Lef-1 and cyclin D1 and activated the angiogenic transcription of vascular endothelial growth factor A （VEGFA）, basic fibroblast growth factor （bFGF）, and insulin-like growth factor 1 （IGF-1）. The angiogenesis process in the 3D collagen model appeared to follow canonical Wnt signaling, and this model can help us understand the importance of the canonical Wnt pathway in the use of ASCs in vascular regeneration.

关键词： Angiogenesis in a 3D model containing adipose tissue stem cells and endothelial cells is mediated by canonical Wnt signaling Wnt

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