Bioengineering & Translational Medicine
·
2023
·
IF 7.4
Jianzhong Zhang,Xue Liu,Yutian Xia,Shuyu Xu,Xuan Liu,Haiqing Xiao,Xiaoyong Wang,Chao Liu,Gang Liu
Melittin, the principal constituent in bee venom, is an attractive candidate for cancer therapy. However, its clinical applications are limited by hemolysis, nonspecific cytotoxicity, and rapid metabolism. Herein, a novel genetically engineered vesicular antibody-melittin (VAM) drug delivery platform was proposed and validated for targeted cancer combination therapy. VAM generated from the cellular plasma membrane was bio-synthetically fabricated, with the recombinant protein (hGC33 scFv-melittin) being harbored and displayed on the cell membrane. The bioactive and targetable nanomelittin conjugated by hGC33 scFv could be released in an MMP14-responsive manner at tumor sites, which reduced off-target toxicity, especially the hemolytic activity of melittin. Importantly, VAM could be loaded with small-molecule drugs or nanoparticles for combination therapy. Nanomelittin formed pores in membranes and disturbed phospholipid bilayers, which allowed the anticancer agents (i.e., chemotherapeutic drug doxorubicin and sonosensitizer purpurin 18 nanoparticles) co-delivered by VAM to penetrate deeper tumor sites, leading to synergistic therapeutic effects. In particular, the punching effect generated by sonodynamic therapy further improved the immunomodulatory effect of nanomelittin to activate the immune response. Taken together, our findings indicate that clinically translatable VAM-based strategies represent a universal, promising approach to multimodal synergetic cancer therapy.
研究领域:
癌症治疗
·
药物递送系统
·
纳米技术
·
生物医学工程
·
药学
·
免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Dongsheng Zhang,Tingting Wang,Xun Zhang,Yuting Xu,Jiang Ming,Xiaoxiao Wang,Zhenfeng Liu,Jingchao Li,Xinhui Su
The primary goal of treating malignant tumors is to efficiently eliminate the primary tumor and prevent metastasis and recurrence. Unfortunately, the immunosuppressive tumor microenvironment (TME) is a significant obstacle to effective oncotherapy. Herein, a therapeutic strategy based on melittin (MLT) encapsulated in hyaluronic acid-modified metal–organic frameworks (MOFs) is pioneered, focusing on the safe delivery and TME-responsive release of MLT to reshaping the immunosuppressive TME and simultaneously activating the immune system to eradicate cancerous cells. Iron-based MOFs respond to glutathione and pH, degrade within a moderately acidic TME, and achieve tumor-specific release of MLT. Additionally, the iron-mediated Fenton reaction produces reactive oxygen species that augment oxidative stress, ultimately leading to tumor-specific ferroptosis, whereas MLT-induced membrane disruption promotes immunogenic cell death to activate the immune system. In combination with the immune checkpoint inhibitor anti-PD-L1, this nanodrug elicits potent antitumor immune responses, facilitating the infiltration of effector T cells and enhancing systemic antitumor T cell immunity to suppress both primary and distant tumors. This study demonstrates the tremendous potential of nanoscale self-destructive MOFs for the targeted transport and controlled release of MLT and reveals the promoting effect of combined MLT and ferroptosis delivery on cancer immunotherapy.
研究领域:
肿瘤学
·
纳米医学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LIFE SCIENCES
·
2020
·
IF 3.647
Li Li,Sufang Zhang,Lei Wei,Zhongfu Wang,Wei Ma,Fangying Liu,Yanhua Shen,Shanfang Zhang,Xiulian Zhang,Yu Hang,Yechang Qian
Aims To investigate the effect and underlying mechanism of melittin and tripartite motif (TRIM) family in human embryonic lung fibroblast (HELF). Materials and methods Lentiviral RNA interference vector and lentiviral overexpression vector were constructed and packaged by transfecting 293T cells; the proliferation of HELF was examined using Cell Counting Kit 8; Western blot and qRT-PCR were performed to examine protein and mRNA expression; the interaction with protein phosphatase magnesium-dependent 1A (PPM1A) was examined by Co-immunoprecipitation. Key findings Compared with the control group, the mRNA expression of the TRIM6, TRIM8 and TRIM47 in the IPF group significantly increased. Melittin inhibited the mRNA expression and protein expression levels of TRIM47, the HELF proliferation, the hydroxyproline levels, and the phosphorylation of Smad2/3; the interference of TRIM47 inhibited the protein expression of Vimentin, α-SMA, CTGF, the phosphorylation of Smad2/3 and the synthesis of hydroxyproline; TRIM47 overexpression elevated the phosphorylation of Smad2/3, induced ubiquitination of PPM1A and decreased the expression level of PPM1A, while TRIM47 RNA interference reversed this result. Significance Melittin has anti-fibrotic effect in HELF by directly reducing the phosphorylation of Smad2/3 or indirectly reducing the phosphorylation of Smad2/3 by decreasing the expression levels of TRIM47 whose overexpression induces ubiquitination of PPM1A.
研究领域:
药理学
·
分子生物学
·
细胞生物学
·
肺纤维化
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2025
·Vol. 31
·期 5
·e70437
·
IF 5
Hai‐Qian Zhang,Yan Wang,Xiao Geng,Mingxin Dong,Ziwei Liu,Chengbiao Sun,Kaikai Yu,Wenwen Xin,Ye Xu,Na Xu,Wensen Liu
ANG‐modified liposomes encapsulating α‐melittin and resveratrol increase their blood–brain barrier penetration and GB cell selectivity. The combined treatment of α‐melittin with resveratrol markedly facilitates apoptosis and pyroptosis, and promotes the apoptosis–pyroptosis switch in the GB cells via downregulating the Wnt/β‐catenin signaling.
研究领域:
药理学
·
肿瘤学
·
神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2018
·Vol. 7
·期 16
·1800380
·
IF 5.609
Hao-Ran Jia,Ya-Xuan Zhu,Ke-Fei Xu,Fu-Gen Wu
Melittin (MEL) is recognized as a highly potent therapeutic peptide for treating various human diseases including cancer. However, the clinical applications of MEL are largely restricted by its severe hemolytic activity and nonspecific cytotoxicity. Here, it is found that MEL can form a stable supramolecular nanocomplex of ≈60 nm with the photosensitizer chlorin e6 (Ce6), which after hyaluronic acid (HA) coating can achieve robust, safe, and imaging-guided tumor ablation. The as-designed nanocomplex (denoted as MEL/Ce6@HA) shows largely reduced hemolysis and selective cytolytic activity toward cancer cells. Upon laser irradiation, the loaded photosensitive Ce6 can synergistically facilitate the membrane-lytic efficiency of melittin and greatly increase the tumor penetration depth of the complexes in multicellular tumor spheroids. In vivo experiments reveal that MEL/Ce6@HA can realize enhanced tumor accumulation, reduced liver deposition, and rapid body clearance, which are beneficial for highly efficient and safe chemo-photodynamic dual therapy. This work develops a unique supramolecular strategy for optimized in vivo delivery of melittin and may have implications for the development of peptide-based theranostics.
研究领域:
药学
·
纳米技术
·
癌症研究
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Yanrui Chen,Xingran Zhang,Fang Li,Jinxing Ma,Zhiwei Wang
Biofouling remains to be one of major obstacles for membrane-based technology in water and wastewater treatment, calling for the development of antibiofouling membranes. For the traditional release-killing strategy, uncontrollable release of biocides and thus a short lifetime as well as the potentially environmental risk are thorny issues for the modified membranes. Herein, hydrophilic hydrogel multilayers with controllable thickness at nanometer scale on a poly(vinylidene fluoride) (PVDF) microfiltration membrane were constructed via layer-by-layer (LbL) self-assembly of non-drug-resistant antimicrobial peptides (AMPs) and alginate . The AMPs/alginate multilayers modified membranes exhibited enhanced hydrophilicity, well-controlled pore size distribution and prominent antimicrobial ability against Escherichia coli and Staphylococcus aureus . As the number of multilayers of alginate increased, both initial and steady release rate of Ponericin G1 reduced; in particular, the AMPs/alginate modified membranes with fifteen multilayers (MSA 15 ) had the slowest release kinetics ( i.e., an initial release rate of 1.79 ± 0.07 μg/cm 2 d and a steady release rate of 0.55 ± 0.03 μg/cm 2 d), resulting in about 60% less release compared with the AMPs/alginate modified membranes with five multilayers (MSA 5 ). Long-term antibiofouling tests showed that the AMPs/alginate modified membranes with ten multilayers (MSA 10 ) exhibited a significantly reduced transmembrane pressure increase rate of 0.81 ± 0.01 kPa/d which was much lower than that of the control membranes (1.80 ± 0.20 kPa/d), mainly attributed to the antibacterial activity imparted by the lasting release of AMPs and competing membrane basic properties. Furthermore, the AMPs/alginate multilayers modified membranes revealed high stability suffering from long-term operation and chemical cleaning cycles. The novel AMP/alginate-incorporated modifying method provides a new dimension to enhance antibiofouling performance of membranes for water and wastewater treatment.
研究领域:
环境工程
·
材料科学
·
水处理
·
膜技术
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 3
·558
·
IF 4.2
Hongyan Yang,Rong Ma,Jiarou Chen,Qian Xie,Wenhui Luo,Pinghua Sun,Zheng Liu,Jialiang Guo
The development of antibiotic-resistant microorganisms is a major global health concern. Recently, there has been an increasing interest in antimicrobial peptides as a therapeutic option. This study aimed to evaluate the triple-action (broad-spectrum antibacterial, anti-biofilm, and anti-quorum sensing activities) of melittin, a membrane-active peptide present in bee venom. The minimum inhibitory concentration and minimum bactericidal concentration of the melittin were determined using the microdilution method and agar plate counting. Growth curve analysis revealed that melittin showed a concentration-dependent antibacterial activity. Scanning electron microscope analysis revealed that melittin treatment altered the morphology. Confocal laser scanning microscope revealed that melittin increased the membrane permeability and intracellular ROS generation in bacteria, all of which contribute to bacterial cell death. In addition, the crystal violet (CV) assay was used to test the anti-biofilm activity. The CV assay demonstrated that melittin inhibited biofilm formation and eradicated mature biofilms. Biofilm formation mediated by quorum sensing (QS) plays a major role in this regard, so molecular docking and molecular dynamics analysis confirmed that melittin interacts with LasR receptors through hydrogen bonds, and further evaluates the anti-QS activity of melittin through the production of virulence factors (pyocyanin, elastase, and rhamnolipid), exopolysaccharides secretion, and bacterial motility, that may be the key to inhibiting the biofilm formation mechanism. The present findings highlight the promising role of melittin as a broad-spectrum antibacterial, anti-biofilm agent, and potential QS inhibitor, providing a new perspective and theoretical basis for the development of alternative antibiotics.Keywords:antimicrobial peptides;melittin;antibacterial;anti-biofilm;anti-quorum sensing
研究领域:
微生物学
·
药理学
·
分子生物学
·
传染病学
✓ 已验证
DOI
PubMed
高影响因子
MATERIALS & DESIGN
·
2015
·
IF 3.501
Xinkun Shen,Fei Zhang,Ke Li,Chenhu Qin,Pingping Ma,Liangliang Dai,Kaiyong Cai
Bacterial infection, a common issue related to orthopedic implantation, is regarded as the second dominant factor resulting in implantation failure. To address the issue, the study reports a novel antibacterial titanium substrate against hyaluronidase secreting bacterium of Staphylococcus aureus , which was fabricated by employing TiO 2 nanotubes (TNTs) to load cecropin B (CecB), and then coating with hyaluronidase sensitive multilayers of chitosan/sodium hyaluronic-cecropin B [(Chi/SH–CecB) 5 ] onto the titanium surfaces via layer by layer technique (TNT–CecB–LBLc). Fourier transform infrared spectroscopy (FITR) and nuclear magnetic resonance ( 1 H NMR) characterizations proved the successful synthesis of SH–CecB. Scanning electron microscopy (SEM), atomic force microscopy (AFM), fluorescence microscopy and water contact angle measurements verified the formation of multilayers onto CecB loaded titanium substrates. The presence of S. aureus and/or exogenous hyaluronidase effectively triggered the degradation of multilayers, thus facilitating the release of CecB from TNTs. The antibacterial evaluations proved that TNT–CecB–LBLc substrates had good early (4 h) and long term (72 h) antibactericidal capacity against both S. aureus and Staphylococcus epidermidis . Moreover, the cellular tests displayed that TNT–CecB–LBLc substrates had relatively good cytocompatibility for osteoblasts, even co-culture with S. aureus . The study provides new insight into the development of bacteria-mediated antibacterial implants for orthopedic application .
研究领域:
材料科学
·
生物材料
·
生物医学工程
·
骨科
·
微生物学
·
纳米技术
✓ 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）