BIOPHYSICAL JOURNAL
·
2022
·
IF 3.699
Shen Wang,Cong Ma
Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) form the SNARE complex to mediate most fusion events of the secretory pathway . The neuronal SNARE complex is featured by its high stability and half-zippered conformation required for driving robust and fast synaptic exocytosis. However, these two features seem to be thermodynamically mutually exclusive. In this study, we have employed temperature-dependent disassociation assays and single-molecule Förster resonance energy transfer (FRET) experiments to analyze the stability and conformation of the neuronal SNARE complex. We reclassified the amino acids of the SNARE motif into four sub-groups (core, core-side I and II, and non-contact). Our data showed that the core residues predominantly contribute to the complex stability to meet a basal requirement for SNARE-mediated membrane fusion , while the core-side residues exert an unbalanced effect on the N- and C-half bundle stability that determines the half-zippered conformation of the neuronal SNARE complex, which would accommodate essential regulations by complexins and synaptotagmins for fast Ca 2+ -triggered membrane fusion. Furthermore, our data confirmed a strong coupling of folding energy between the N- and C-half assembly of the neuronal SNARE complex, which rationalizes the strong potency of the half-zippered conformation to conduct robust and fast fusion. Overall, these results uncovered that the stability profile of the neuronal SNARE complex reflects its potency to drive fast and robust membrane fusion. Based on these results, we also developed a new parameter, the stability factor ( F s ), to characterize the overall stability of the neuronal SNARE complex and resolved a linear correlation between the stability and inter-residue coulombic interactions of the neuronal SNARE complex, which would help rationally design artificial SNARE complexes and remold functional SNARE complexes with desirable stability.
研究领域:
细胞生物学
·
生物物理学
✓ 已验证
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-20
·
IF 15.7
Cui Lele,Cui Yongsheng,Liu Jing,Li Wei,Wu Mengdan,Wei Xiawei,Lai Ying,Mi Peng
A major obstacle in knocking down oncogenes for tumor therapy is the efficient delivery of siRNA into the cytosolic spaces of cancer cells. Here, we genetically bioengineer biomimetic nanovesicles with tumor-recognition and enzyme-controlled membrane fusion functions for efficiently delivering small interfering RNA into cancer cells towards gene silencing tumor therapy. The siRNA@eS-BNVs are formulated by encapsulating siRNA inside the core and coating with genetically engineered HEK293T ACE2- cell membranes encoded with functional S protein, which can recognize cancer cells and initiate membrane fusion when triggered by the enzyme. The siRNA@eS-BNVs demonstrate better efficacy for cytosolic siRNA delivery and RNA interference than conventional formulations. By intravenous injection, siRNA@eS-BNVs are highly accumulated in tumors and potently inhibited tumor and lung metastasis by simultaneously silencing the epidermal growth factor receptor gene in vivo. The cancer cell-targeting and enzyme-activatable nanovesicles provide a valuable strategy for effective and precise drug delivery.
研究领域:
生物工程
·
肿瘤学
·
分子生物学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF SURFACTANTS AND DETERGENTS
·
2022
·Vol. 25
·期 5
·643-654
·
IF 1.972
Yu Zhao,Chenyu Liu,Hailiang Chen,Hengjun Zhou,Simiao Yu,Deze Mi,Shuli Yue,Weihong Qiao
Liposomes are the predominant drug delivery system widely used in the pharmaceutical industry, but rapid clearance and endosome degradation are the main barriers to improve the delivery efficiency of liposomes, especially for protein or genes. Simulating viral membrane fusion peptides, four asymmetrically dihydrophobic chain polyethylene glycol (PEG) lipids with long circulating and membrane fusion properties have been designed and synthesized with a high yield. The structure of synthetic PEG lipids is characterized by 1 H NMR and mass spectrometry. The critical micelle concentrations of PEG lipids are lower by one or two orders of magnitude compared with traditional surfactants such as SDBS or SDS, which show excellent self-assembly performance of lipids. The size and morphology of liposomes constituted with neutral lipid DOPC and PEG lipid are characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). In the conditions of 50% ethanol and 5–25 mmol L −1 Ca 2+ , the PEG neutral lipid complexes encapsulated pEGFP are almost neutral with a diameter below 300 nm.
研究领域:
药学
·
生物化学
·
材料科学
✓ 已验证
产品关联
DOI
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2025
·
IF 10.5
Jixuan Han,Xiaoran Liu,Ying Yan,Jingwen Ge,Han Zhao,Chen Wang,Guohong Song,Ling Zhu,Yanlian Yang
Extracellular vesicle miRNAs (EV-miRNAs) are strongly linked to cancer progression, metastasis, and drug resistance, making them promising biomarkers for precision diagnosis. However, the clinical potential of EV-miRNA-based liquid biopsies is hindered by the low abundance of EV-miRNAs and the tedious detection procedure including EV separation, purification and miRNA quantification. Here, we develop a novel one-step catalytic hairpin assembly (CHA)-based fluorescent assay for sensitive detection of EV-miRNAs assisted with DNA-mediated membrane fusion (DMF) and DNA tetrahedron (DT) (DMF-DT-CHA). This DMF-DT-CHA assay facilitates the membrane fusion between liposome and EV through interactions between DNAs for DT-CHA probe delivery into EVs, and followed by DT-CHA, which recognizes target miRNAs to initiate non-enzymatic signal amplification via CHA-based fluorescence emission. We analyzed EVs from three breast cancer cell sources using DMF-DT-CHA and the results were consistent with qPCR and the platform achieved the limit of detection (LoD) of 0.24 fM for EV-miRNAs. We performed a clinical evaluation of the DMF-DT-CHA assay platform. Recipient operating characteristic curves (ROCs) showed that the DMF-DT-CHA platform was an excellent classifier for distinguishing breast cancer (BC) patients from healthy donors and breast cancer patients from benign breast nodule patients, with area under the curve (AUC) values of 0.850 and 0.835, respectively, as well as an accuracy of 81.1% in response to treatment for triple-negative breast cancer. DMF-CT-CHA assay platform has clinical potential for cancer diagnosis and treatment monitoring.
研究领域:
生物化学
·
分子生物学
·
临床医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Bio Materials
·
2018
·
IF 0
Huimin He,Jinyang Li,Xiaodong Cao,Changshun Ruan,Qi Feng,Hua Dong,Gregory F. Payne
Chitosan is an aminopolysaccharide that can be physically cross-linked through two independent, reversible, and pH-switchable mechanisms. At high pH, neutral chitosan chains can self-assemble to form crystalline domains that serve as one type of physical cross-link (such cross-linked hydrogels are designated Chit0). At low pH, the chains are cationic and dis-assembled from each other but can be electrostatically cross-linked by multivalent anionic micelles of sodium dodecyl sulfate (such cross-linked hydrogels are designated SDS-Chit-H+). Here, we report that the ability to reversibly reconfigure cross-linking mechanisms provides a means to fuse separately prepared chitosan films. Experimentally, neutral Chit0 hydrogel films were first prepared by cathodic electrodeposition, and then separately prepared Chit0 films were fused by overlapping them in the presence of SDS and acid. Qualitative evidence demonstrates fusion across the interface at both the microscale (e.g., SEM) and macroscale. Mechanical testing (e.g., tear test) demonstrates that fusion leads to strong bonding with failure occurring in the bulk region of the film and not at the joint. Potentially, the ability to fuse separately prepared films may provide new opportunities for additive manufacturing of biobased materials.
研究领域:
生物材料学
·
高分子化学
✓ 已验证
产品关联
DOI
PubMed
Bioactive Materials
·
2021
·
IF 14.593
Yin Shi,Xiaoqian Feng,Liming Lin,Jing Wang,Jiaying Chi,Biyuan Wu,Guilin Zhou,Feiyuan Yu,Qian Xu,Daojun Liu,Guilan Quan,Chao Lu,Xin Pan,Jianfeng Cai,Chuanbin Wu
Enveloped viruses such as SARS-CoV-2 frequently have a highly infectious nature and are considered effective natural delivery systems exhibiting high efficiency and specificity. Since simultaneously enhancing the activity and selectivity of lipopeptides is a seemingly unsolvable problem for conventional chemistry and pharmaceutical approaches, we present a biomimetic strategy to construct lipopeptide-based mimics of viral architectures and infections to enhance their antimicrobial efficacy while avoiding side effects. Herein, a surface-nanoengineered antimicrobial liposome (SNAL) is developed with the morphological features of enveloped viruses, including a moderate size range, lipid-based membrane structure, and highly lipopeptide-enriched bilayer surface. The SNAL possesses virus-like infection to bacterial cells, which can mediate high-efficiency and high-selectivity bacteria binding, rapidly attack and invade bacteria via plasma membrane fusion pathway, and induce a local “burst” release of lipopeptide to produce irreversible damage of cell membrane. Remarkably, viral mimics are effective against multiple pathogens with low minimum inhibitory concentrations (1.6–6.3 μg mL −1 ), high bactericidal efficiency of >99% within 2 h, >10-fold enhanced selectivity over free lipopeptide, 99.8% reduction in skin MRSA load after a single treatment, and negligible toxicity. This bioinspired design has significant potential to enhance the therapeutic efficacy of lipopeptides and may create new opportunities for designing next-generation antimicrobials.
研究领域:
生物医学工程
·
药剂学
·
微生物学
✓ 已验证
DOI
PubMed
高影响因子
CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
·
2024
·
IF 1.2
Jiamei LI,An YAN,Mingquan WANG,Di LI
Targeted delivery of proteins into desired cell groups is crucial for disease therapy and cellular functionalization. However, current delivery methods face severe side effects and off-target problems, making it difficult to achieve cell-targeted protein delivery. Herein, we developed a user-friendly membrane fusion liposome for cancer cell-targeted protein delivery. Phosphorothioated DNA-mediated membrane fusion was employed as an efficient transmembrane delivery approach. The phosphorothioated DNA was capped with the AS1411 aptamer, which specifically recognizes nucleolar proteins on the cancer cell membrane, enabling a controllable delivery of proteins into targeted cancer cells. This delivery system exhibited commendable biocompatibility and targeted delivery ability, thereby realizing highly effective cancer cell inhibition in vitro. The in vivo results further suggested that the membrane protein-responsive membrane fusion delivery system offers a new avenue for highly biocompatible and targeted protein delivery.
研究领域:
生物化学
·
药物递送系统
·
肿瘤学
✓ 已验证
产品关联
DOI
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2017
·
IF 4.581
Dongguo Lin,Yinzhu Luo,Guang Yang,Fangfang Li,Xiangkun Xie,Daiwei Chen,Lifang He,Jingyu Wang,Chunfeng Ye,Shengsheng Lu,Lin Lv,Shuwen Liu,Jian He
Influenza A viruses (IAVs) induce acute respiratory disease and cause significant morbidity and mortality throughout the world. With the emergence of drug-resistant viral strains, new and effective anti-IAV drugs with different modes of action are urgently needed. In this study, by conjugating cholesterol to the N-terminus of the short peptide KKWK, a lipopeptide named S-KKWK was created. The anti-IAV test indicated that S-KKWK and its derivatives displayed potent antiviral activities against a broad variety of influenza A viral strains including oseltamivir-resistant strains and clinically relevant isolates with IC 50 values ranging from 0.7 to 3.0 µM. An extensive mechanistic study showed that these peptides functioned as viral “entry blockers” by inhibiting the conformational rearrangements of HA2 subunit, thereby interrupting the fusion of virus-host cell membranes. Significantly, a computer-aided docking simulation and protein sequence alignment identified conserved residues in the stem region of HA2 as the possible binding site of S-KKWK, which may be employed as a potential drug target for designing anti-IAVs with a broad-spectrum of activity. By targeting this region, a potent anti-IAV agent was subsequently created. In addition, the anti-IAV activity of S-KKWK was assessed by experiments with influenza A virus-infected mice, in which S-KKWK reduced the mortality of infected animals and extended survival time significantly. Overall, in addition to providing a strategy for designing broad-spectrum anti-IAV agents, these results indicate that S-KKWK and its derivatives are prospective candidates for potent antivirals.
研究领域:
病毒学
·
药物化学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2024
·
IF 13
Siwen Chen,Haibo Lan,Minyi Liu,Chenxi He,Qiuyu Li,Shuting Zheng,Yinfei Zheng,Zede Wu,Tiancai Liu,Bingxia Zhao
Biomimetic camouflaged nanocarriers coated with cancer cell membranes (CCMs) have attracted considerable research attention for drug delivery application. CCM-camouflaged nanocarriers have inherent tumor-homologous targeting ability. However, they enter cancer cells via endocytosis, which is not efficient for drug delivery. Switching the internalization mechanism to membrane fusion may enhance their delivery efficiency. In this study, an innovative biomimetic-targeting nanocarrier is designed by hybridizing CCMs with pH-sensitive liposomes (1,2-dioleoyl-sn-glycero-3-phosphoethanolamine liposomes, DOPE-Lipo), named as CCMpHD. The presence of CCMs makes the nanocarriers capable of homologous targeting, and the DOPE-Lipo hybrid allows the nanocarriers to achieve efficient internalization via membrane fusion. Notably, the cellular uptake of CCMpHD is significantly higher than that of the CCMs. The most efficient delivery is achieved with 1/10 CCMs, which requires remarkably less cell membranes. Doxorubicin (DOX) is used as a model drug to characterize the homologous targeting drug delivery properties of the hybrid nanocarriers. Both in vitro and in vivo experiments demonstrated that the nanocarriers exhibited satisfactory biosafety and enhanced tumor-targeted delivery. With enhanced delivery efficiency whilst requiring fewer CCMs, these hybrid membrane nanocarriers provides a new strategy for CCM-based drug delivery in cancer treatment.
研究领域:
生物医学工程
·
肿瘤学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Zide Chen,Dongyang Wei,Qi Wang,Qing Gou,Jiaywei Tsauo,Qicong Mai,Xiumei Chen,Xiaowen Cai,Xiaoming Chen,Jing Zhang
The nanodelivery carrier was modified with tumor cell membrane and dendritic cell membrane to create a double-membrane fusion biomimetic nanomedicine, termed FM@mPDA/DOX/JQ-1. This research introduces a biologically inspired platform for multimodal combined tumor therapy. Because fusion membrane nanomedicines inherit the homologous targeting properties of tumor cells, chemotherapy drugs can be delivered to tumor lesions. In addition, the fusion membrane carries abundant and complete tumor cell membrane antigens. Based on the professional antigen presentation characteristics of dendritic cells, it directly or indirectly promotes the uptake of cell membrane-bound tumor antigens and downstream immune responses. In ectopic and orthotopic tumor-bearing mouse models, FM@mPDA/DOX/JQ-1 can induce a durable immune response to inhibit the rebound of primary tumors after chemotherapy and photothermal therapy (PTT). FM@mPDA/DOX/JQ-1 demonstrates no adverse impact on liver and kidney function, as well as blood indicators in mice, affirming its excellent safety profile. This tumor-specific immunotherapy-based nanoplatform holds promise for extension across various tumor types, offering a viable approach for multimodal combined tumor therapy.
研究领域:
肿瘤学
·
纳米医学
·
免疫学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Materials Chemistry B
·
2025
·
IF 5.7
Qi Xie,Yuan Gao,Wei Chen,Haoyu Zhang,Chuansheng Fu,Samira Batur,Yixuan Zhou,Yang Li,Jiao Zhang,Li Kong,Zhiping Zhang
Cancer therapy based on extracellular vesicles faces several practical challenges, such as low production, inadequate stability, and inefficiency, making it difficult to achieve ideal therapeutic effects. Herein, a novel engineering technology of EVs was developed based on the autonomous "fusion-exocytosis" process. Primarily, membrane fusogenic liposomes (MFLs) with unique physical and chemical properties were engineered by tailoring the components, which could interact with cells to achieve mutual fusion of lipid membranes and release corresponding fusogenic extracellular vesicles (FEVs). As an inducer of immunogenic cell death (ICD) and enhancer of EV production, monensin (Mon) was incorporated into MFLs. The synergistic action of MFLs and Mon not only increased the production of released FEVs but also significantly enhanced their immunogenicity, effectively promoting DC maturation. Consequently, the obtained FEVs effectively inhibited tumor growth in the treatment of by activating anti-cancer immune responses. This engineering method of generating FEVs could effectively increase production and obtain highly immunogenic extracellular vesicles, which would facilitate their clinical translation for cancer therapy.
研究领域:
生物工程
·
免疫学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xi Wang,Weimin Wan,Guiquan Liu,Tangjun Ren,John Osilama Thomas,Haonan Wu,Chen An,Fei Tian,Yan Zhu,Alexander Kros,Jian Yang
The complementary fusogenic coiled-coil lipopeptides CPE and CPK have gained attention as mediators of drug delivery via membrane fusion for various therapeutic applications. However, the models used in these studies were mainly 2D cell cultures and animal models, leaving the in-site interaction and physiological effects of this lipopeptide system in vivo unclear. To address this, we constructed two 3D cell models in vitro , a mimicking lung organ (mLO) using 3D printed hydrogel cell scaffold and alveolar organoids (AOs) derived from mouse adult stem cells. These models were used to evaluate the lipopeptide modified membrane fused drug delivery system (MF-DDS) and show the details of drug delivery in treating acute lung injury (ALI) model based on the 3D models. Our results revealed that MF-DDS demonstrated superior drug delivery efficiency in mLO, particularly when cultured dynamically on a chip compared to a static U-shaped plate. Importantly, the MF-DDS demonstrated great biocompatibility with no significant changes in macrophage phenotype, inflammatory cytokine secretion, and lung barrier integrity on the mLO after the cell membrane fused with the artificial lipid membrane. In the lipopolysaccharide (LPS) induced injury model using mLO, the MF-DDS delivered naringin effectively, significantly reduced inflammatory factor secretion, macrophage polarization, and protected lung barrier disruption. Furthermore, the safety and effectiveness of MF-DDS were validated using AOs, underscoring its potential in treating ALI. These findings offer critical insights into the interactions between MF-DDS and organ systems, paving the way for faster and more precise evaluations of drug delivery strategies for disease treatment.
研究领域:
药理学
·
生物医学工程
·
细胞生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）