Yunfeng Lin

• M.D., Ph.D.
• Sichuan University

Repairing and reconstructing massive bone defects remains a critical clinical challenge. Recruiting early stem cells, and promoting their angiogenesis and osteogenesis are crucial for the initiation of efficient in situ bone regeneration and repair. This study aims to promote bone regeneration and reconstruct massive bone defects using tetrahedral...

Osteoarthritis (OA) is a chronic joint disease that causes a gradual deterioration of articular cartilage. A major challenge in OA treatment is the limited penetration and delivery efficiency of drugs to cartilage and chondrocytes due to the rapid clearance of drugs through synovial fluid in joints and the osmotic barrier of the cartilage extracell...

In the development of nasal‐to‐brain (N2B) drug delivery systems, the key challenge lies in penetrating the mucus, crossing the nasal epithelial barrier, and achieving broad distribution within the central nervous system (CNS) while ensuring biosafety. Non‐biomimetic delivery systems raise concerns regarding metabolism, while biomimetic systems, th...

Diabetic periodontitis presents a unique therapeutic challenge, primarily due to its chronic inflammatory profile and the associated bone loss driven by immune dysregulation. Metformin (Met) is recognized for its potent anti‐inflammatory properties, yet its limited cellular uptake has hindered its clinical effectiveness in diabetic periodontitis. A...

Bacterial infections resistant to antimicrobial treatments, particularly those caused by Pseudomonas aeruginosa (P. aeruginosa), frequently lead to elevated mortality rates. Tackling this resistance using therapeutic combinations with varied mechanisms has shown considerable promise. In this study, a bioinspired nanocarrier is successfully designed...

MicroRNA (miRNA)‐based therapy holds significant potential; however, its structural limitations pose a challenge to the full exploitation of its biomedical functionality. Framework nucleic acids are promising owing to their transportability, biocompatibility, and functional editability. MiRNA‐125 is embedded into a nucleic acid framework to create...

Extensive accumulation of senescent cells contributes to organismal aging, and slowing down the process of cellular senescence may ameliorate age‐related pathologies. Targeted inhibition of the mechanistic target of rapamycin complex 1 (mTORC1) is found to suppress the conversion of cells to senescence. The regulatory‐associated protein of mTOR (Ra...

In designing aerosolized drugs, the challenge lies in achieving optimal penetration and retention. Existing delivery systems prioritize larger particles for prolonged intrapulmonary retention, compromising penetration speed. Conversely, smaller nanoparticles face rapid clearance and limited retention. RNA sponges featuring multiple microRNA binding...

Cell‐surface engineering holds great promise in boosting endogenous stem cell attraction for tissue regeneration. However, challenges such as cellular internalization of ligand and the dynamic nature of cell membranes often complicate ligand–receptor interactions. The aim of this study is to harness the innovative potential of programmable tetrahed...

Craniofacial bone defects, caused by trauma, congenital abnormalities, or various diseases, present a significant challenge in regenerative medicine. One approach to addressing this problem is the use of RNA interference...

Infected wounds are a complex disease involving bacterial infections and dysregulated inflammation. However, current research has mostly focused on bacterial inhibition rather than on inflammation. Thus, combined therapeutic strategies with anti‐bacterial and anti‐inflammation efficacies are urgently needed. Antibiotics are the main treatment strat...

Unnecessary exposure to ionizing radiation (IR) often causes acute and chronic oxidative damages to normal cells and organs, leading to serious physiological and even life-threatening consequences. Amifostine (AMF) is a validated radioprotectant extensively applied in radiation and chemotherapy medicine, but the short half-life limits its bioavaila...

Diabetes mellitus (DM) is characterized by elevated blood glucose and advanced glycation end product (AGEs) levels. Increased AGEs in bone tissue inhibit osteogenic differentiation by bone marrow mesenchymal stem cells (BMSCs), leading to bone loss and osteoporosis in diabetic patients. Enhancing the osteogenic differentiation capacity of BMSCs in...

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 strategies. In patients with diabetes, the increased levels of ferroptosis affect the osteogenic commitment and differentiation of bone mesenchymal stem cells (BMSC...

Osteoporosis (OP) is a common disease characterized by bone loss and bone tissue microstructure degradation. Drug treatment is a common clinical treatment that aims to increase bone mass and bone density. Tetrahedral DNA nanostructures (TDNs) are three‐dimensional tetrahedral frames formed by folding four single‐stranded DNA molecules, which have g...

Hydrocephalus is one of the most common brain disorders and a life‐long incurable condition. An empirical “one‐size‐fits‐all” approach of cerebrospinal fluid (CSF) shunting remains the mainstay of hydrocephalus treatment and effective pharmacotherapy options are currently lacking. Macrophage‐mediated ChP inflammation and CSF hypersecretion have rec...

Systemic immune monitoring is a crucial clinical tool for disease early diagnosis, prognosis and treatment planning by quantitative analysis of immune cells. However, conventional immune monitoring using flow cytometry faces huge challenges in large-scale sample testing, especially in mass health screenings, because of time-consuming, technical-sen...

Since its discovery in 1978, cisplatin‐based chemotherapy regimens have served a pivotal role in human cancer treatment, saving millions of lives. However, its high risk still poses a significant challenge for cisplatin‐induced acute kidney injury (AKI), which occurs in 30% of cisplatin‐treated patients. Unfortunately, no effective solution for pre...

There has been considerable interest in gene vectors and their role in regulating cellular activities and treating diseases since the advent of nucleic acid drugs. MicroRNA (miR) therapeutic strategies are research hotspots as they regulate gene expression post‐transcriptionally and treat a range of diseases. An original tetrahedral framework nucle...

Introduction: The application of DNA framework nucleic acid materials in the biomedical field has witnessed continual expansion. Among them, tetrahedral framework nucleic acids (tFNAs) have gained significant traction as the foremost biological vectors due to their superior attributes of editability, low immunogenicity, biocompatibility, and biode...

Antibody drug conjugates (ADCs) have shown promise to be the mainstream chemotherapeutics for advanced HER2-positive cancers, yet the issues of poor drug delivery efficiency, limited chemotherapeutic effects, severe immune responses, and drug resistance remain to be addressed before the clinical applications of ADCs. The DNA aptamer-guided drug con...

Skin photodamage, which is induced by ultraviolet (UV) radiation, is a prevalent cause of skin damage. In this study, a transdermal drug delivery system is developed for the topical treatment of skin photodamage, which is composed of tetrahedral framework nucleic acids (tFNAs) and lipoic acid (LA). The tFNAs‐LA (TLA) nanocomposite exhibits excellen...

MicroRNAs (miRNAs) regulate several physiological and pathological processes involved in various diseases, including osteoarthritis (OA). OA is the most common global musculoskeletal disorder, characterized by the irreversible progressive destruction of articular cartilage. Supplementation with exogenous miRNAs may represent a promising therapeutic...

Resistance to traditional antiepileptic drugs is a major challenge in chronic epilepsy treatment. MicroRNA-based gene therapy is a promising alternative but has demonstrated limited efficacy due to poor blood-brain barrier permeability, cellular uptake, and targeting efficiency. Adenosine is an endogenous antiseizure agent deficient in the epilepti...

Major depressive disorder (MDD) is a common illness with an increasing lifetime prevalence. Thus, an increasing number of studies have investigated the association between MDD and microRNAs (miRNAs), which are a novel approach for treating depression. However, the therapeutic potential of miRNA-based strategies has several limitations. To overcome...

Osteonecrosis of the femoral head (ONFH) is recognized as a common refractory orthopedic disease that causes severe pain and poor quality of life in patients. Puerarin (Pue), a natural isoflavone glycoside, can promote osteogenesis and inhibit apoptosis of bone mesenchymal stem cells (BMSCs), demonstrating its great potential in the treatment of os...

Nanomaterials are often used as immunomodulators because they can be tailored by a controllable process. In this work, a complex based on a tetrahedral framework nucleic acid delivery system and MicroRNA-155, known as T-155, is synthesized for the modulation of immunosuppression. In vivo, T-155 ameliorated spleen and thymus damage and hematopoiesis...

An active targeting strategy-enabled DNA tetrahedron delivery vehicle could facilitate stable drug encapsulation and stimuli-responsive on-demand release, building a universal platform for different drug delivery requirements. Owing to the excellent biocompatible nature, programmability and remarkable cell and tissue permeability, the tetrahedral D...

The significant clinical feature of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the exposure of the necrotic jaw. Other clinical manifestations include jaw pain, swelling, abscess, and skin fistula, which seriously affect the patients’ life, and there is no radical cure. Thus, new methods need to be found to prevent the occurrence of...

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 re...

Growing evidence indicates that the tumor microenvironment (TME) can be combined with other therapeutic modalities, including cytotoxic chemotherapy and targeted therapies, to produce unanticipated results in oncology treatment. Here, we proposed a novel bacterial nanomaterial capable of targeting peritumoral biofilm and modulating TME. It was base...

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...

Rheumatoid arthritis (RA), a chronic autoimmune disease (AD), can cause irreversible loss of joint function. The methotrexate (MTX) is the first-line choice in the treatment of RA; however, its efficacy is limited due to its insolubility in water and lack of targeting ability. The development of nucleic acid nano system provides new prospect for it...

Axon Regeneration In article number 2202513, Sirong Shi, Yungfeng Lin, and co‐workers report a multifunctional tetrahedral‐framework nucleic acids system, denoted as MiDs. The peripheral nervous system is like a vibrant rainforest. As flexible in conformation as cats, the powerful MiDs enhance the role of macrophages (represented by the fireflies)...

DNA Nanotechnology Tetrahedral framework nucleic acids have attracted extensive attention as a static drug nanocarrier. In article number 2201731, Xiaxiao Cai and co‐workers report a dynamic lysosome‐activated tetrahedral nanobox for completely encapsulating short interfering RNA. The closed tetrahedral structure endows cargo RNA with active releas...

Although checkpoint-inhibitor immunotherapy held tremendous advances, improving immune response during treatment has always been an urgent clinical issue. With the help of mRNA microarray technology, it was found that short rod-like nanohydroxyapatite (nHA) promoted the upregulation of CD274 and PD-L1 related gene transcription, which was confirmed...

Alzheimer's disease is a neurodegenerative disease caused by excessive amyloid β protein-induced neurotoxicity. However, drugs targeting amyloid β protein production face many problems, such as the low utilization rate of drugs by cells and the difficulty of drugs in penetrating the blood-brain barrier. A tetrahedral framework nucleic acid is a new...

Triple-negative breast cancer (TNBC) is a subtype of breast cancer, and it has aggressive and more frequent tissue metastases than other breast cancer subtypes. Because the proliferation of TNBC tumor cells does not depend on estrogen receptor (ER), progesterone receptor (PR), and Erb-B2 receptor tyrosine kinase 2 (HER2) and lacks accurate drug tar...

Some chemotherapeutic agents, such as anthracyclines and oxaliplatin, can induce immunogenic cell death (ICD) with additional immune responses against cancer. However, ICD-based immunotherapy is limited by the nonspecific distribution of drugs and various side effects. Here, an immunostimulatory self-assembled tetrahedral framework nucleic acid (tF...

Sepsis has affected millions of people worldwide with high mortality rate and lack of effective strategies. Previous studies have reported that quercetin (Que) can attenuate lipopolysaccharide (LPS)‐Induced sepsis. However, for poor water solubility, low bioavailability, and instability, the application of Que is limited. Hence, a nano‐system is co...

Astrocytes, as the most plentiful subtypes of glial cells, play an essential biphasic function in ischemic stroke (IS). However, although having beneficial effects on stroke via promoting nerve restoration and limiting lesion extension, astrocytes can unavoidably cause exacerbated brain damage due to their participation in the inflammatory response...

MicroRNA (miR)‐based therapy shows strong potential; however, structural limitations pose a challenge in fully exploiting its biomedical functionality. Tetrahedral framework DNA (tFNA) has proven to be an ideal vehicle for miR therapy. Inspired by the ancient Chinese myth “Sun and Immortal Birds,” a novel bioswitchable miR inhibitor delivery system...

As major complications of chemoradiotherapy, myelosuppression and hematopoietic‐system damage severely affect immunologic function and can delay or even terminate treatment for cancer patients. Although several specific cytokines have been used for hematopoiesis recovery, their effect is limited, and they may increase the risk of tumor recurrence....

The cover image is based on the Original Article MiR‐26a‐tetrahedral framework nucleic acids mediated osteogenesis of adipose‐derived mesenchymal stem cells by Xiaoru Shao et al., https://doi.org/10.1111/cpr.13272.

Objectives: Delivery systems that provide time and space control have a good application prospect in tissue regeneration applications, as they can effectively improve the process of wound healing and tissue repair. In our experiments, we constructed a novel micro-RNA delivery system by linking framework nucleic acid nanomaterials to micro-RNAs to...

Tetrahedral framework nucleic acids (tFNAs) have attracted extensive attention as drug nanocarriers because of their excellent cellular uptake. However, for oligonucleotide cargos, tFNA mainly acts as a static delivery platform generated via sticky‐ended ligation. Here, inspired by the original stable space inside the tetrahedral scaffold, we fabri...

The hyperplasia and destruction of synovial tissue have an important impact on the development of rheumatoid arthritis (RA), the abnormal proliferation and migration of synovial fibroblast in synovial tissue is similar to tumor cells. Targeting anomalous synovial fibroblast and designing a high bioavailability nano drug delivery system can reduce t...

Tetrahedral DNA nanostructures (TDNs) are molecules with a pyramidal structure formed by folding four single strands of DNA based on the principle of base pairing. Although DNA has polyanionic properties, the special spatial structure of TDNs allows them to penetrate the cell membrane without the aid of transfection agents in a caveolin-dependent m...

Objectives: The purpose of this study was to investigate the treatment effect and molecular mechanism of tetrahedral framework nucleic acids (tFNAs), novel self-assembled nucleic acid nanomaterials, in diffuse BMEC injury after SAH. Materials and methods: tFNAs were synthesized from four ssDNAs. The effects of tFNAs on SAH-induced diffuse BMEC i...

DNA materials have emerged as potential nanocarriers for targeted cancer therapy to precisely deliver cargos with specific purposes. The short half‐life and low bioavailability of DNA materials due to their interception by the reticuloendothelial system and blood clearance further limit their clinical translation. This study employs an HER2‐targete...

Rapid and efficient tools for early cancer detection have diagnostic and therapeutic value. Given that the DNA hairpin-based hybridization chain reaction (HCR) is effective in detecting various biological targets, a tetrahedral framework DNA-enhanced (TDN-enhanced) HCR detection system (T-probe system) is introduced for cancer-related targets and i...

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...

Tetrahedral framework nucleic acid (tFNA), a special DNA nanodevice, is widely applied in diverse biomedical fields. Due to its high programmability, biocompatibility, tissue permeability as well as its capacity for cell proliferation and differentiation, tFNA presents a powerful tool that could overcome potential barriers in the treatment of neuro...

Delivery System for microRNA In article number 2104359, Xiaoxiao Cai and co-workers present a tetrahedral framework nucleic acids-based delivery system for miRNA. miRNA is protected extracellularly, and efficiently released in response to intracellular RNase after cellular entrance. Similarly, Chinese philosophy “Chuang Tzu” portrayed the transform...

MicroRNAs (miRs) play an important role in regulating gene expression. Limited by their instabilities, miR therapeutics require delivery vehicles. Tetrahedral framework nucleic acids (tFNAs) are potentially applicable to drug delivery because they prominently penetrate tissue and are taken up by cells. However, tFNA‐based miR delivery strategies ha...

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 therapeutics. With the rapid progress in DN...

Neuroinflammation plays a significant role in inducing depression-like behavior. Tetrahedral DNA nanostructures (TDNs) are molecules that exhibit anti-inflammatory properties and can effectively penetrate the blood-brain barrier. Thus, researchers have hypothesized that TDNs regulate the secretion of proinflammatory cytokines and consequently allev...

The facial nerve is a crucial nerve in the maxillofacial region and is vulnerable to damage. As a consequence of the complications during nerve restoration, existing remedies have certain limitations, thus the treatment of facial nerve injury is always a perplexing task for people. Regulation of Schwann cells is always the breakpoint of neurorestor...