Advanced Healthcare Materials
·
2024
·
IF 10
Meng-Meng Chen,Han-Wen Tian,Yuan-Qiu Cheng,Yu-Xin Yue,Yu-Chen Pan,Dong-Sheng Guo
Snakebite is a medical emergency that often leads to high mortality and morbidity in tropical and subtropical regions. The diversity in venom composition between various types of snakes necessitates the use of different specific antivenom treatments, which presents clinical and financial challenges in the management of snakebites. Therefore, developing a broad-spectrum antidote to neutralize complex and diverse snake venoms has assumed critical importance. Herein, a broad-spectrum antidote is developed through molecular recognition and coassembly to neutralize four kinds of snake venom toxins, those are three-finger toxin (3FTx), snake venom metalloproteinase (SVMP), phospholipase A 2 (PLA 2 ), and snake venom serine protease (SVSP), which have high abundance and toxicity. The coassembly of sulfonate-modified amphiphilic calixarene (SCA) and amphiphilic cyclodextrin (CD) is employed to neutralize the toxicity of 3FTx, 1,2-dodecanedithiol (DDT) and thioetheramide phosphorylcholine (TEAPC) are introduced through coassembly to neutralize toxicity of SVMP and PLA 2 , respectively, and the nafamostat (NT), which can be loaded through the host-guest complexation, is employed to neutralize toxicity of SVSP. The broad-spectrum antidote, NT@SCA/CD/DDT/TEAPC, effectively neutralizes key toxins from the most medically important cobra and vipers, significantly improving survival rates of poisoned mice. This study conceptually validated the feasibility of broad-spectrum detoxification and also offers a conveniently integrated supramolecular strategy.
研究领域:
医学
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生物化学
·
药理学
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2025
·
IF 26.8
Siyuan Qian,Xuan Wang,Yishun Guo,Wenfang He,Jianhua Yang,Hao Chen,Renlong Li,Lili Su,Xinyi Wang,Yi Shao,Bailiang Wang
In the treatment of infectious keratitis, therapeutic strategies often prioritize enhancing bactericidal efficacy. However, endotoxins released from Gram-negative bacteria cause inflammatory reaction, leading to corneal structural damage and scar formation. Given that polymyxin B (PMB) can bind and neutralize lipopolysaccharide (LPS), this study employs large-pore mesoporous silica nanoparticles (lMSNs) grafted with PMB as carriers for cationic antibacterial carbon quantum dots (CQDs) to prepare CQD@lMSN-PMB, which enables synchronous sterilization and endotoxin neutralization. In the acidic infectious microenvironment, the accelerated release of CQDs eliminates 99.88% bacteria within 2 h, effectively substituting immune mediated sterilization. Notably, CQD@lMSN-PMB exhibits exceptional LPS neutralization performance (2.22 µg LPS/mg CQD@lMSN-PMB) due to its high specific surface area. In an infectious keratitis model, inflammation subsides significantly within the first day of CQD@lMSN-PMB intervention and is completely resolved by day 3. By day 2, interleukin-1β, interleukin-6 and tumor necrosis factor-α in CQD@lMSN-PMB group decrease by 86.99%, 91.15%, and 77.56%, respectively, compared to the CQDs-only sterilization group. Ultimately, corneal integrity and transparency are preserved, with suppressed expressions of fibrosis-related factors including matrix metalloproteinase 9, transforming growth factor-β and α-smooth muscle actin. Therefore, this synchronous sterilization and endotoxin neutralization strategy outperforms monotherapy strategies focused solely on sterilization or endotoxin neutralization.
研究领域:
眼科学
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纳米医学
·
感染性疾病
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产品关联
DOI
PubMed
高影响因子
Matter
·
2023
·
IF 18.9
Cheng Gao,Cheryl H.T. Kwong,Mian Tang,Jinwei Liu,Hiotong Kam,Shengke Li,Simon M.Y. Lee,Chunhai Fan,Hua-Zhong Yu,Ruibing Wang
Antibiotic-resistant strains have emerged, and endotoxins vary greatly in their structural motifs across bacterial species, limiting the clearance efficiency of structure-specific anti-endotoxin antibodies. This study constructs intracellularly gelated macrophages (GMs) with an intact membrane structure to neutralize bacteria and endotoxins via receptor-ligand interaction and share the bacterial burden to ameliorate in vivo infection without considering their molecular structure. Furthermore, GMs derived from bacterially infected macrophages (here referred to as bacterially engineered macrophages) are found to have upregulated membrane pathogen-related receptors for strengthened bacterium and endotoxin recognition and increased the membrane zeta potential to reduce the electrostatic repulsion force for facile GM-bacterium surface interaction. Bacterially engineered GMs achieve efficient management of sepsis and wound infection and targeted alleviation of bacterial pneumonia. The top-down fabrication of GMs provides a universal neutralization strategy against bacterial infection, and bacterially engineered host immune cells, upon intracellular gelation, demonstrate a natural cell engineering venue to obtain comprehensive neutralization decoys.
研究领域:
免疫学
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微生物学
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纳米医学
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转化医学
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感染性疾病
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生物材料
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分子生物学
✓ 已验证
DOI
高影响因子
Biomaterials Research
·
2023
·Vol. 27
·期 1
·1-16
·
IF 11.3
Li Chengnan,Gan Yingying,Li Zongshao,Fu Mengjing,Li Yuzhen,Peng Xinran,Yang Yongqiang,Tian Guo-bao,Yang Yi Yan,Yuan Peiyan,Ding Xin
Background
P. aeruginosa , a highly virulent Gram-negative bacterium, can cause severe nosocomial infections, and it has developed resistance against most antibiotics. New therapeutic strategies are urgently needed to treat such bacterial infection and reduce its toxicity caused by endotoxin (lipopolysaccharide, LPS). Neutrophils have been proven to be able to target inflammation site and neutrophil membrane receptors such as Toll-like receptor-4 (TLR4) and CD14, and exhibit specific affinity to LPS. However, antibacterial delivery system based on the unique properties of neutrophils has not been reported. Methods A neutrophil-inspired antibacterial delivery system for targeted photothermal treatment, stimuli-responsive antibiotic release and endotoxin neutralization is reported in this study. Specifically, the photothermal reagent indocyanine green (ICG) and antibiotic rifampicin (RIF) are co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP-ICG/RIF), followed by coating with neutrophil membrane to obtain antibacterial delivery system (NM-NP-ICG/RIF). The inflammation targeting properties, synergistic antibacterial activity of photothermal therapy and antibiotic treatment, and endotoxin neutralization have been studied in vitro. A P. aeruginosa -induced murine skin abscess infection model has been used to evaluate the therapeutic efficacy of the NM-NP-ICG/RIF. Results Once irradiated by near-infrared lasers, the heat generated by NP-ICG/RIF triggers the release of RIF and ICG, resulting in a synergistic chemo-photothermal antibacterial effect against P. aeruginosa (~ 99.99% killing efficiency in 5 min). After coating with neutrophil-like cell membrane vesicles (NMVs), the nanoparticles (NM-NP-ICG/RIF) specifically bind to inflammatory vascular endothelial cells in infectious site, endowing the nanoparticles with an infection microenvironment targeting function to enhance retention time. Importantly, it is discovered for the first time that NMVs-coated nanoparticles are able to neutralize endotoxins. The P. aeruginosa murine skin abscess infection model further demonstrates the in vivo therapeutic efficacy of NM-NP-ICG/RIF. Conclusion The neutrophil-inspired antibacterial delivery system (NM-NP-ICG/RIF) is capable of targeting infection microenvironment, neutralizing endotoxin, and eradicating bacteria through a synergistic effect of photothermal therapy and antibiotic treatment. This drug delivery system made from FDA-approved compounds provides a promising approach to fighting against hard-to-treat bacterial infections.
研究领域:
药学
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纳米技术
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传染病
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2023
·
IF 18.9
Meng Cheng,Caihua Ye,Chunxiao Tian,Dongju Zhao,Haonan Li,Zuhao Sun,Yuyang Miao,Qiang Zhang,Junping Wang,Yan Dou
Immune recognition of excessive neurotoxins by microglia is a trigger for the onset of neuroinflammation in the brain, leading to neurodegeneration in Alzheimer's disease (AD). Blocking active recognition of microglia while removing neurotoxins holds promise for fundamentally alleviating neurotoxin-induced immune responses, but is very challenging. Herein, an engineered macrophage-biomimetic versatile nanoantidote ( [email protected] ) is developed for inflammation-targeted therapy against AD by neurotoxin neutralization and immune recognition suppression. Coating macrophage membranes can not only endow [email protected] with anti-phagocytic and inflammation-tropism capabilities to target inflammatory lesions in AD brain, but also efficiently reduce neurotoxin levels to prevent them from activating microglia. The loaded oxytocin (OT) can be slowly released to downregulate the expression of immune recognition site Toll-like receptor 4 (TLR4) on microglia, inhibiting TLR4-mediated pro-inflammatory signalling cascade. Benefiting from this two-pronged immunosuppressive strategy, [email protected] exhibits outstanding therapeutic effects on ameliorating cognitive deficits, inhibiting neuronal apoptosis, and enhancing synaptic plasticity in AD mice, accompanied by the delayed hippocampal atrophy and brain microstructural disruption by in vivo 9.4T MR imaging. This work provides new insights into potential AD therapeutics targeting microglia-mediated neuroinflammation at the source.
研究领域:
神经科学
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药理学
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纳米技术
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免疫学
·
神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）