Small
·
2025
·
IF 12.1
Huihui Chen,Xiao Hu,Bingying Hou,Liying Qin,Eve-Graciella M.E.K. Kuete,Levinus Hendrik Koole
Bacterial keratitis (BK) is a critical and sight-threatening corneal infection that significantly impairs the quality of life. Due to the widespread antibiotic-resistant microbes and the slow development in antibiotics, there is an increasingly growing demand to create new antimicrobial agents for the treatment of BK. Herein, copper-intercalated molybdenum disulfide (Cu-MoS 2 ) nanosheets are constructed by intercalating Cu into the interlayer structure of MoS 2 via intercalation chemistry, which not only introduces the Fenton reaction but also modulates the electronic structure of MoS 2 . Cu-MoS 2 can convert H 2 O 2 into more toxic reactive oxygen species (ROS), thereby exhibiting excellent bactericidal performance against Staphylococcus aureus (S. aureus) , methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli) at room temperature in the dark. Animal experiments indicated that Cu-MoS 2 can effectively treat BK caused by MRSA. This work demonstrates that intercalation chemistry as a novel and effective strategy to tune MoS 2 as the antibacterial agent with no reliance on light that has great potential therapeutic effects on clinical drug-resistant BK.
研究领域:
医学
·
材料科学
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DOI
PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2020
·
IF 2.365
Guigang Li,Lingjuan Xu,Menglin Jiang,Xianggen Wu
The aim was to reveal the characteristic profiles of the marketed levofloxacin eye drops (5 mg/ml) and levofloxacin eye gel (3 mg/g) from the pharmacokinetics and pharmacodynamics views of rabbits’ eyes. A mild and a heavy bacterial keratitis models in rabbits were established. Different regimens of levofloxacin eye drops and eye gel, including phosphate buffer solution (the PBS group), the 4-Sol + 1-Gel group (rabbits were treated with 4 doses of levofloxacin eye drops and 1 dose levofloxacin eye gel per day), the 3-Sol + 1-Gel group (3 doses drops and 1 dose gel), the 4-Sol group (4 doses drops), the 4-Gel group (4 doses gel), the 3-Sol group (3 doses drops), and the 3-Gel group (3 doses gel), were applied to evaluate their efficacies. The ocular pharmacokinetics of levofloxacin eye drops and gel were also investigated. The results of mild infection groups showed that all treatment regimens significantly relieved the infection symptoms, and the treatment effect followed this order: 4-Gel > 4-Sol + 1-Gel > 3-Sol + 1-Gel > 4-Sol > 3-Gel > 3-Sol. In the heavy infection groups, all the treatment regimens significantly relieved the infection symptoms, and the treatment effect also followed the order with the mild infection results. All treatment regimens lowered the number of corneal colony forming units (CFU). Levofloxacin eye gel significantly increased intraocular penetration in rabbits’ eyes. It can be concluded that the levofloxacin eye gel was more effective in treating bacterial keratitis than the levofloxacin eye drops in rabbit keratitis model with a proper treatment regimen such as 4-Gel.
研究领域:
药理学
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眼科医学
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Lifang Chen,Yao Wang,Xiuqing Huang,Lifang Han,Zhengwei Huang,Ling Guo,Kai Chen,Guoxin Tan
The occurrence of bacterial keratitis (BK) presents a significant threat to ocular health, often leading to visual impairment. Currently, conventional antibiotic therapies tend to promote bacterial resistance and lack biocompatibility. Therefore, it is of great significance to develop an alternative product with safe and efficient antimicrobial properties. In this study, we developed a novel smart pH-responsive nano-antibacterial system (PM/Ag-Ce6@ZIF-8) based on a metal-organic framework (MOF), enabling specific bacterial targeting and photodynamic therapy. By utilizing bacteria-specific maltodextrin transport pathway, the intelligent nano-antibacterial modified with maltotriose can accurately discriminate between bacterial infection and normal tissue, specifically target the site of infection, and efficiently accumulate at the infection site to enhance safety and efficacy. Furthermore, the incorporation of silver nanoparticles enhances the effectiveness of MOF photodynamic therapy by effectively eradicating bacteria. The nano-antibacterial system exhibits potent inhibition of biofilm formation as well as antibacterial activity while demonstrating excellent in vitro and in vivo biocompatibility. In an animal model of bacterial keratitis, PM/Ag-Ce6@ZIF-8 exhibits superior antibacterial activity compared to Levofloxacin (LVFX) eye drops, significantly improving therapeutic outcomes for bacterial keratitis in mice. Hence, this intelligent nano-antibacterial platform holds promising potential for clinical applications in treating keratitis.
研究领域:
医学
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生物材料学
·
纳米技术
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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
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感染性疾病
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2020
·
IF 7.727
Haijie Han,Yifan Gao,Mengyin Chai,Xiaobo Zhang,Shaorui Liu,Yue Huang,Qiao Jin,Andrzej Grzybowski,Jian Ji,Ke Yao
Infectious keratitis caused by bacterial biofilms is one of the main causes of corneal blindness, presenting a serious threat to public health. In this study, matrix metalloproteinase (MMP)-sensitive supramolecular nanoparticles (denoted as MMP-S NPs) were constructed for enhancing photodynamic antibacterial effect against biofilm-associated bacterial keratitis . MMP-S NPs were prepared by host-guest self-assembly of chlorin e6 (Ce6) conjugated β-cyclodextrin (β-CD) prodrug (β-CD-Ce6) and MMP-9-sensitive peptides (YGRKKKRRQRRR-GPLGVRG-EEEEEE) terminated with adamantane (Ad) (Ad-MMP-S PEPs). MMP-S NPs with EEEEEE peptide shell had a negatively charged surface, preventing adhesion to the normal ocular surface or healthy corneal cells, thus enhancing tear retention time. After arriving at the infected lesions, the protective EEEEEE peptide shell of MMP-S NPs was removed, triggered by overexpressed MMP-9 in the keratitis microenvironment. The subsequently exposed cationic peptides helped the nanoparticles penetrate and accumulate in biofilms as well as bind to Gram-negative bacteria Pseudomonas aeruginosa ( P. aeruginosa) , which eventually improved the photodynamic antibacterial effect. Furthermore, the P. aeruginosa keratitis model verified the high effectiveness of a topical eye drop formulation of MMP-S NPs in killing bacteria by destroying the bacterial membrane as a result of in situ photodynamic activation of reactive oxygen species (ROS) formation under light irradiation. Moreover, the inflammatory response in the cornea was inhibited to a great extent. As a result, further damage to the corneal tissue was completely suppressed. This research provides a viable antibacterial alternative to fight against bacterial keratitis through effective elimination of infectious bacteria and eradication of bacterial biofilms in the cornea.
研究领域:
医学
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药理学
·
感染病学
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DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Jing Xiang,Ruifen Zou,Pin Wang,Xinfangzi Wang,Xuefei He,Fang Liu,Chen Xu,Aiguo Wu
As bacterial keratitis progresses rapidly, prompt intervention is necessary. Current diagnostic processes are time-consuming and invasive, leading to improper antibiotics for treatment. Therefore, innovative strategies for diagnosing and treating bacterial keratitis are urgently needed. In this study, Cu 2-x Se@BSA@NTRP nanoparticles were developed by loading nitroreductase-responsive probes (NTRPs) onto Cu 2-x Se@BSA. These nanoparticles exhibited integrated fluorescence imaging and antibacterial capabilities. In vitro and in vivo experiments showed that the nanoparticles produced responsive fluorescence signals in bacteria within 30 min due to an interaction between the released NTRP and bacterial endogenous nitroreductase (NTR). When combined with low-temperature photothermal therapy (PTT), the nanoparticles effectively eliminated E. coli and S. aureus , achieved antibacterial efficacy above 95% and facilitated the re-epithelialization process at the corneal wound site in vivo . Overall, the Cu 2-x Se@BSA@NTRP nanoparticles demonstrated potential for rapid, noninvasive in situ diagnosis, treatment, and visualization assessment of therapy effectiveness in bacterial keratitis.
研究领域:
医学
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生物材料学
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纳米医学
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DOI
PubMed
高影响因子
Smart Medicine
·
2024
·
IF 0
Xiwen Geng,Nan Zhang,Zhanrong Li,Mengyang Zhao,Hongbo Zhang,Jingguo Li
The development of non-antibiotic pharmaceuticals with biocompatible and efficient antibacterial properties is of great significance for the treatment of bacterial keratitis. In this study, we have developed antibacterial iron-doped nanozymes (Fe 3+ -doped nanozymes, FNEs) with distinguished capacity to fight against bacterial infections. The iron-doped nanozymes are composed of Fe 3+ doped zeolitic imidazolate framework-8 (Fe/ZIF-8) and polyethylene imide (PEI), which were functionally coated on the surface of Fe/ZIF-8 and imparted the FNEs with improved water dispersibility and biocompatibility. FNEs possess a significant spontaneous peroxidase-mimic activity without the need for external stimulation, thus elevating cellular reactive oxygen species level by catalyzing local H 2 O 2 at the infection site and resulting in bacteria damaged to death. FNEs eliminated 100% of Staphylococcus aureus within 6 h, and significantly relieved inflammation and bacterial infection levels in mice bacterial keratitis, exhibiting higher bioavailability and a superior therapeutic effect compared to conventional antibiotic eye drops. In addition, the FNEs would not generate drug resistance, suggesting that FNEs have great potential in overcoming infectious diseases caused by antimicrobial resistant bacteria.
研究领域:
生物学
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医学
·
药理学
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材料科学
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DOI
ACS Nano
·
2025
·
IF 16
Xiaojie Wu,Xin Wang,Jing Kang,Alideertu Dong,Ying-Wei Yang
Staphylococcus aureus (S. aureus) is a prevalent and highly virulent pathogen responsible for microbial keratitis, which can lead to stromal damage, corneal perforation, and even blindness. In the postantibiotic era, the escalating prevalence of antibiotic-resistant S. aureus has rendered conventional antibiotic treatments increasingly ineffective, particularly due to autoinducing peptide-mediated signaling. Meanwhile, antibiotics disrupt the balance of the microbiota, which can further trigger ocular complications. To address these challenges, we designed and prepared a camouflaged bacterial system, supramolecular-coated S. aureus (SMCS), which can identify and aggregate with the matching pathogenic S. aureus through autoinducing peptide-mediated signaling. Upon the addition of amantadine, competitive host–guest interactions trigger the release of the antibacterial agent, enabling efficient and selective sterilization against pathogenic S. aureus with a fourfold higher efficacy than that against beneficial bacteria. In a rat model of bacterial keratitis, the proportion of Staphylococcus is 13.71% in the cornea after SMCS treatment, which is comparable to that in the healthy cornea (7.40%). SMCS+amantadine treatment can effectively eradicate bacteria, increase the diversity and abundance of corneal microorganisms, and preserve the balance of the corneal microbiota, providing promising clinical prospects in bacterial infection treatments and bacterial-mediated bioapplications.
研究领域:
微生物学
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眼科学
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感染性疾病
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纳米医学
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分子生物学
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转化医学
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抗菌治疗
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DOI
PubMed
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
·
2021
·Vol. 139
·期 12
·51815
·
IF 3.125
Onome Ejeromedoghene,Yi Ping Hu,Olayinka Oderinde,Fang Yao,Caroline Akinremi,Richard Akinyeye,Sheriff Adewuyi,Guodong Fu
There have been numerous challenges in the incorporation of photochromic materials into hydrogel system due to the agglomeration of nanoparticles and non-transparency of the hydrogel material. In this study, WO 3 nanocomposites were prepared and incorporated into poly(hydroxyethyl acrylate) (pHEA) and polyacrylamide (pAAm) to fabricate poly(HEA-AAm)/WO 3 hydrogels with improved coloration efficiency and reversibility. The as-prepared p(HEA-AAm)/WO 3 hydrogel displayed remarkable mechanical properties to sustain compressive and tensile stress up to 15.9 and 58.7 MPa with deformation ratios of 16.2 and 30.8, respectively. The hydrogels exhibited good transmittance (%T) and reflectance (%R) of ~47% and 64% at 829 and 408 nm respectively. The hydrogels also revealed visible spectroscopic absorbance at >781 nm after exposure to UV-lamp and natural sunlight for 5 s and 0.5 h, giving rise to a blue coloration, however, the fading process of the hydrogels was achieved in 20 min and 2.0 h respectively in an open air. More so, the hydrogel solutions displayed a high antibacterial efficacy against bacteria pathogens associated with bacterial keratitis in contact lens care solutions. The observed excellent photochromic and antibacterial properties of the hydrogel show promising potentials for use in the construction of antibacterial contact lenses, optical and intelligent devices.
研究领域:
材料科学
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生物材料
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光学
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生物医学工程
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DOI
高影响因子
RSC Advances
·
2021
·Vol. 11
·期 42
·26160-26167
·
IF 3.361
Rui Wang,Duoduo Lu,Hui Wang,Haoyu Zou,Ting Bai,Chulei Feng,Quankui Lin
Contact lenses (CLs) are an important medical device for ophthalmic disease treatment. They can be used not only to correct refractive errors, such as myopia, but also can serve as a drug carrier for ocular surface disease treatment. In this study, a therapeutic CL was designed for bacterial keratitis treatment by constructing an antibacterial surface coating via a layer-by-layer (LbL) electrostatic self-assembly method. Vancomycin-incorporated chitosan nanoparticles were firstly prepared by ionic condensation of sodium tripolyphosphate (abbreviated as CTVNP). The positively charged CTVNP were then used for LbL deposition with negatively charged heparin (HEP), obtaining a (HEP/CTVNP)n polyelectrolyte multilayer on the CL surface. It is shown that such antibiotic incorporated surface coating doesn't influence the light transmittance of the CL, so it should not affect the patients' visual acuity when wearing them. The in vitro bacteriostatic effect evaluation was performed via live and dead bacteria staining and scanning electron microscope (SEM), which demonstrated the effective antibacterial property of such a surface. The fabricated therapeutic CL was then used to treat bacterial keratitis on a rabbit model. The results showed that such CL could effectively control the development of the bacteria-infected cornea and had a significant therapeutic effect.
研究领域:
眼科学
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材料科学
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药学
·
生物医学工程
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
LiLi Zhao,Hongbo Li,Jiajia Yuan,Zhen Wang,Dan Xu,Zhenbin Liu,Lishan Yao,Junjian Ran,Quanyu Dai,Liangbin Hu
Bacterial keratitis is one of the most common causes of visual impairment and blindness worldwide, and suffers the risk of drug-resistant infections due to the abuse of antibiotics. Despite its ability to counteract antibiotic resistance by inducing ferroptosis, the application of Fe 2+ is limited by oxidative instability and a solution pH often incompatible with ophthalmic use. Thus, this study designed and synthesized an ascorbate–ferrous iron complex (SA-Fe(II)) using ferrous lactate and sodium ascorbate, followed by comprehensive structural characterization. Results confirmed the formation of coordination bonds between Fe 2+ and sodium ascorbate. The molecular ion peak and characteristic decarboxylated fragment, along with broad and diffuse diffraction peaks in X-ray diffraction patterns, verified the formation of an amorphous metal chelate structure stabilized by dynamic coordination bonds. The SA-Fe(II) complex exhibited potent antibacterial activity, achieving more than 99.99 % killing of Staphylococcus aureus ( S. aureus ) and methicillin-resistant Staphylococcus aureus (MRSA) at 100 μM within 3 h. When incorporated into a sodium hyaluronate eye-drop matrix (SA-Fe(II)-SH), the formulation exhibited excellent ocular biocompatibility, as evidenced by hemolysis rates less than 5 %, more than 95 % viability of human corneal epithelial cells (HCE-T) corneal epithelial cells over 3 days, and no observable tissue inflammation in vivo. Importantly, in a mice model of MRSA keratitis, SA-Fe(II)-SH significantly reduced bacterial load, suppressed the production of inflammatory cytokines (IL-1β, IL-6, TNF-α), promoted corneal repair, and prevented systemic dissemination. This non-antibiotic strategy integrates antibacterial, anti-inflammatory, and pro-healing functions, offering a safe and effective therapeutic approach for the treatment of drug-resistant bacterial keratitis.
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PubMed
高影响因子
Cell Reports Physical Science
·
2024
·
IF 7.9
Yuzhuo Fan,Fanfan Chen,Wanzhong Yuan,Yuchun Sun,Jiarui Li,Yan Li,Mingwei Zhao,Xu Zhang,Kai Wang
Contact lens (CL)-associated bacterial keratitis (BK), a prevalent and underestimated disorder caused by unhygienic CL wear, poses a risk to permanent loss of visual acuity. Clinically, low drug-delivery efficiency, frequent administration, hormone complications, and antibiotic resistance remain the major unsolved challenges. Here, we introduce a chlorogenic acid (CGA)-conjugated CL material based on gelatin methacrylate via cryogelation(cGelMA/CGA-CL) to strengthen the prevention and treatment of BK. The cGelMA/CGA-CL features a highly moist, macroporous, adjustable structure for sustained release of CGA and is favorably biocompatible to cells, providing antimicrobial protection against opportunistic pathogens and inhibiting excessive ocular inflammatory responses through the JAK2-STAT1/STAT2 signaling pathway. Furthermore, the cGelMA/CGA-CL effectively alleviates the symptoms of BK with immunoregulation of macrophage recruitment and anti-inflammatory factor release in a mouse model of BK. The cGelMA/CGA-CL offers a promising candidate for the prevention and treatment of BK, which may significantly reduce the risk of infection for CL wearers.
研究领域:
眼科学
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生物材料
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药学
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免疫学
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生物医学工程
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产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）