MOLECULAR PHARMACEUTICS
·
2020
·
IF 4.321
Zhe Wang,Xingyun Liu,Ying Peng,Meng Su,Saibin Zhu,Jian Pan,Ben Shen,Yanwen Duan,Yong Huang
Platensimycin (PTM) is a promising natural product drug lead against Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), while the clinical development was hampered by problems related to its poor solubility and pharmacokinetic properties. In this study, we used liposomes and micelles as carriers of PTM to prepare PTM nanoformulations for the treatment of MRSA infection in mice. PTM-loaded nanoparticles could effectively reduce residual bacteria in the MRSA-infected macrophage cell model, comparing to free PTM. More importantly, in vivo studies showed that encapsulation of PTM by liposomes or micelles effectively improved the pharmacokinetic properties of PTM in Sprague–Dawley rats and the survival rate of MRSA-infected C57BL/6J mice. Our study has thus suggested that the clinically used nanocarriers, such as liposome and micelle, might also be useful to improve the efficacy of other natural product drug leads to accelerate their in vivo evaluation and preclinical development.
研究领域:
微生物学
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药理学
·
纳米医学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Zhe Wang,Xingyun Liu,Yanwen Duan,Yong Huang
Skin and soft tissue infections require effective and sustained topical administration. Platensimycin (PTM) is a natural drug lead that targets bacterial fatty acid synthases and has a great potential to treat infections caused by methicillin-resistant Staphylococcus aureus (MRSA). To facilitate the use of PTM against local MRSA infections, we prepared polyacrylamide hydrogels containing polyamidoamine (PAMAM)/PTM nanoparticles (NP-gel(PTM)) for the controlled release of PTM. NP-gel(PTM) can continuously inhibit the growth of MRSA and its biofilm formation in simulated drug flow models in vitro. In situ implantation of NP-gel(PTM) could treat MRSA-infected subcutaneous soft tissues without toxicity. For MRSA-infected skin wounds, NP-gel(PTM) not only showed strong anti-MRSA activity but also accelerated more wound healing than the widely used antibiotic mupirocin. Collectively, PTM is expected to be used in this safe and effective NP-gel delivery platform for the treatment of local infections, which might help to alleviate the current antibiotic resistance crisis.
研究领域:
药理学
·
生物材料
·
感染病学
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产品关联
DOI
PubMed
高影响因子
Infection and Drug Resistance
·
2023
·
IF 3.9
Huaqiao Tang,Nana Long,Lin Lin,Yao Liu,Jianlong Li,Fenghui Sun,Lijuan Guo,Fen Zhang,Min Dai
Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a very damaging and widespread pathogen, which is associated with many diseases and causes serious infections. MRSA infection can modulate the effects of drugs, which may occur through an influence on cytochrome P450 (CYP450), the drug-metabolizing enzyme in the liver. In this study, we evaluated the underlying mechanism of drug failure or poisoning in MRSA infection.Materials and methods: Mice were infected with three different doses of MRSA and the changes in CYP450 expression, cytokines, and oxidative stress markers were evaluated.Results: The administration of an attack dose of MRSA caused serious symptoms of infection and resulted in a 40% mortality rate in the mice. MRSA induced strong inflammation and oxidative stress in the mice, predominantly caused by significant increases in interleukin (IL)-1β, IL-4, IL-6, macrophage inflammatory protein, glutathione S-transferase (GST), and malondialdehyde, and decreases in oxygen radical absorbance capacity and glutathione levels in the liver. The expression of IL-2, tumor necrosis factor-α, and GST was briefly suppressed, but increased on days 3 and 7. The increased inflammation and oxidative stress further induced a significant decrease in the mRNA levels and activities of CYP450 1A2, 2D22, 2E1, and 3A1 in MRSA-infected mice within the first day of infection.Conclusion: These results show that MRSA infection leads to inflammation and oxidative stress, and reduces the expression levels and activities of drug metabolism enzymes, which decreased drug metabolism in patients infected with MRSA. Therefore, to avoid a drug overdose, the plasma concentration of patients with MRSA infection should be continuously monitored.
研究领域:
医学
·
药理学
·
免疫学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Kai Lv,Zhen Wang,Wenjun He,Zijing Feng,Hui Xing,Yuanfang Jiang,Yingtong Lu,Jingjie Shang,Bin Guo,Hao Xu,Guowei Li,Bo Ning,Dong Ma
Nitric oxide (NO) as a promising therapeutic molecule for infection treatments is impeded by challenges of precise delivery and accumulation in treating deep tissue infections, such as osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA). Herein, a bacterial-targeting liposome (MN@Mal-Lips) assembled by maltotriose (Mal)-modified cholesterol and lecithin was presented for synergistic NO/methicillin (MET) therapy of MRSA-infected osteomyelitis. MN@Mal-Lips were specifically internalized by MRSA via Mal transporters and thus targetedly accumulated at deep MRSA-infected site. Attributed to the capabilities of NO to induce biofilm dispersal and reverse bacterial resistance, the precisely delivered NO combined with MET facilitating efficient bacterial eradication by disrupting bacterial cell membrane and damaging bacterial DNA. Furthermore, MN@Mal-Lips relieved the local inflammation by potentiating the polarization of macrophages to M2-type while suppressing the M1-type. Meanwhile, MN@Mal-Lips promoted the proliferation, migration, and mineralization of osteoblast, as well as upregulated osteogenesis-related genes, thus repairing the bone tissue. Together, this bacterial-targeting NO-delivery liposome system offers an effective therapeutic strategy for clinical management of MRSA-induced osteomyelitis and may provide great possibilities in the development of NO therapy combating with deep tissue infections caused by drug-resistant bacteria.
研究领域:
药学
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微生物学
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医学
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产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Caihong Lin,Zunwei Ma,Yunpeng Gao,Mengqi Le,Zhifeng Shi,Dawei Qi,Jian-Chao Ma,Zhong-Kai Cui,Lin Wang,Yong-Guang Jia
Antibiotic-resistant bacterial infections have led to an increased demand for antibacterial agents that do not contribute to antimicrobial resistance. Antimicrobial peptides (AMPs) with the facially amphiphilic structures have demonstrated remarkable effectiveness, including the ability to suppress antibiotic resistance during bacterial treatment. Herein, inspired by the facially amphiphilic structure of AMPs, the facially amphiphilic skeletons of bile acids (BAs) are utilized as building blocks to create a main-chain cationic bile acid polymer (MCBAP) with macromolecular facial amphiphilicity via polycondensation and a subsequent quaternization. The optimal MCBAP displays an effective activity against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli, fast killing efficacy, superior bactericidal stability in vitro, and potent anti-infectious performance in vivo using the MRSA-infected wound model. MCBAP shows the low possibility to develop drug-resistant bacteria after repeated exposure, which may ascribe to the macromolecular facial amphiphilicity promoting bacterial membrane disruption and the generation of reactive oxygen species. The easy synthesis and low cost of MCBAP, the superior antimicrobial performance, and the therapeutic potential in treating MRSA infection altogether demonstrate that BAs are a promising group of building blocks to mimic the facially amphiphilic structure of AMPs in treating MRSA infection and alleviating antibiotic resistance.
研究领域:
生物化学
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微生物学
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药理学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Peiyuan Li,Huan Liao,Yingbin Lv,Siyan Liang,Jingwen Zhong,Wei Su
Wound infections are a primary cause of delayed wound healing, and film dressings have garnered significant attention in wound management. However, the development of biologically sourced and green-synthesized film dressings with rapid antimicrobial functionality remains an urgent technological breakthrough. In this study, we successfully developed gelatin sodium alginate/sea sheath molecularly modified berberine hydrochloride film (GS/CB). The incorporation of sea sheath powder significantly enhances the mechanical properties of the gelatin‑sodium alginate film.The calcium ions (Ca 2+ ) provided by the sea sheath create a cross-linking effect within the sodium alginate-gelatin network, resulting in tensile properties of the GS/CB films that are 2.6 times greater than those of the control films. This enhancement allows the films to meet the requirements for wound applications. In in vitro antimicrobial experiments, the films incorporated with sodium oleate-modified berberine hydrochloride showed good antimicrobial effects, with an inhibition rate of 97.79 % against Staphylococcus aureus ( S. aureus ) and 98.57 % against methicillin-resistant Staphylococcus aureus ( MRSA ). In in vivo wound healing experiments, the film effectively eliminated MRSA from the wound, achieving a bacterial clearance rate of 98.5 %. Compared to transparent film dressings, the GS/CB film demonstrated superior wound care efficacy and significantly accelerated wound healing. Furthermore, both in vivo and in vitro tests indicated that the film possesses excellent biocompatibility. Therefore, the GS/CB film holds great potential and application value as a new wound dressing for the treatment of infectious wounds.
研究领域:
生物材料学
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医学
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抗菌材料研究
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Guowei Li,Xiaohua Wei,Kai Lv,Dongna Xie,Mei Liu,Yi Xu,Dong Ma,Genlong Jiao
MRSA -induced arthritis is a prevalent and highly debilitating orthopedic condition. The inflammatory response induced by bacterial infection hinders tissue repair and exacerbates bone loss. Traditional antibiotic therapies are limited by low bioavailability, substantial side effects, and narrow efficacy, rendering them inadequate for comprehensive treatment of arthritis. Nitric oxide (NO) has demonstrated considerable potential in overcoming bacterial resistance, modulating immune responses, and facilitating tissue repair. Therefore, a stage-specific NO release strategy, tailored to the distinct phases of bacterial arthritis, is essential for effective treatment. In this study, mesoporous polydopamine nanoparticles were utilized as NO donors (mPDA/NONOate) and encapsulated within a supramolecular hydrogel formed via the host-guest interaction between α-cyclodextrin (α-CD) and Pluronic F127. The injectable nature of the resulting NO/PDA-Gel hydrogel ensured uniform distribution within irregular bone joint infection sites, minimizing NO donor loss and enhancing local bioavailability. Notably, upon near-infrared (NIR) irradiation, the hydrogel induces a rapid increase in local temperature, facilitating rapid NO release. At the same time, the synergistic photothermal effect effectively kills bacteria and rapidly controls the infection. Without light irradiation, NO is sustainably and stably released from the NO/PDA-Gel, modulating the bone immune microenvironment, alleviating inflammation, promoting chondrocyte proliferation and differentiation, and accelerating bone tissue repair, thus significantly shortening the healing time of MRSA -induced arthritis. In conclusion, the injectable self-assembled NO/PDA-Gel offers a precise, stage-matched therapeutic approach for MRSA -induced arthritis and holds promise for the treatment of deep-seated infections caused by other multidrug-resistant pathogens.
研究领域:
医学
·
生物材料学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Tian Huang,Jing Zhao,Haijun Li,Wei Zhou,Jintao Wang,Jianliang Shen,Jicai Chen,Xiangwen Liao
Infections caused by methicillin-resistant Staphylococcus aureus ( MRSA ) are a significant public health challenge, necessitating the development of innovative antibacterial strategies. Nanomaterials are recognized for their ability to serve as photothermal conversion agents, transforming light energy into heat for antibacterial applications. These materials act as biological enzymes capable of generating reactive oxygen species (ROS), leveraging their catalytic activity to combat infections. While they show considerable promise, enhancing their ROS-generating efficiency and overall catalytic performance remains a critical challenge. In this work, a high catalytic bimetallic nanoplatform was developed, building on “large electronegativity difference induction/etch-assisted/diffusion termination” mechanism to improve antibacterial efficacy. The synthesized nanoparticles were found to exhibit exceptional photothermal conversion efficiency and surface defects, enabling efficient bacterial eradication. Both in vitro and in vivo experiments demonstrated that H-Pt 3 Sn nanoparticles effectively eliminated MRSA while significantly inhibiting and disrupting biofilms formed by the pathogen. The nanoparticles also facilitated tissue repair by modulating macrophage-related molecular markers. In conclusion, this study presents a promising photothermal synergistic nanosystem with high catalytic functionality for advanced anti-infective applications.
研究领域:
生物医学工程
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材料科学
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抗菌研究
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产品关联
DOI
高影响因子
Biomaterials Advances
·
2025
·
IF 6
Zini Huang,Yihan Ma,Xinyi Yang,Xiaoping Yang,Yinjia Cheng,Aiqing Zhang
Persistent microbial infections and excessive reactive oxygen species (ROS) accumulation severely impede diabetic wound healing. Herein, we developed an ultrasound-switchable BiVO 4 /fullerene piezoelectric heterostructure via a one-pot solvothermal method, enabling on-demand transition between bactericidal action and ROS scavenging for treating infected diabetic wounds. Under 8-min ultrasound (US) irradiation, the heterojunction sonosensitizer leveraged piezoelectric polarization to generate substantial ROS in real-time through a narrowed energy band gap and enhanced charge carrier separation and migration efficiency, resulting in the disruption of bacterial membrane integrity and 99.9 % eradication of methicillin-resistant Staphylococcus aureus (MRSA). Upon US withdrawal, the sonosensitizer spontaneously transitioned to an antioxidative state through fullerene-mediated ROS scavenging, effectively neutralizing excess ROS and restoring cellular redox balance. In an MRSA-infected diabetic wound model, this ultrasound-responsive duality effectively suppressed bacterial proliferation, reduced inflammation, enhanced angiogenesis, and ultimately accelerated wound healing within 14 days. This ultrasound-switchable therapeutic strategy offers promising insights for managing drug-resistant infections and other ROS-mediated biomedical challenges.
研究领域:
生物医学工程
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材料科学
·
微生物学
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产品关联
DOI
PubMed
高影响因子
Nano Convergence
·
2024
·Vol. 11
·期 1
·1-22
·
IF 13.4
Chen Sunfang,Yao Jun,Huo Shicheng,Xu Chennan,Yang Ruting,Tao Danhua,Fang Bin,Ma Gaoxiang,Zhu Zaihua,Zhang Ye,Guo JingJing
Hydrogel-based delivery systems have now emerged as a pivotal platform for addressing chronic tissue defects, leveraging their innate capacity to suppress pathogenic infections and facilitate expedited tissue regeneration. In this work, an injectable hydrogel dressing, termed AgNPs-dermal matrix hydrogel (Ag@ADMH), has been designed to expedite the healing process of wounds afflicted with methicillin-resistant Staphylococcus aureus (MRSA), featuring sustained antibacterial efficacy. The synthesis of the hydrogel dressing entailed a self-assembly process of collagen fibers within an acellular dermal matrix to construct a three-dimensional scaffold, encapsulated with plant polyphenol-functionalized silver nanoparticles (AgNPs). The Ag@ADMH demonstrated exceptional biocompatibility, and enables a sustained release of AgNPs, ensuring prolonged antimicrobial activity. Moreover, the in vitro RT-qPCR analysis revealed that compared with ADMH, Ag@ADMH diminish the expression of iNOS while augmenting CD206 expression, thereby mitigating the inflammatory response and fostering wound healing. Especially, the Ag@ADMH facilitated a reduction in M1 macrophage polarization, as evidenced by a significant decrement in the M1 polarization trend and an enhanced M2/M1 ratio in dermal matrix hydrogels laden with AgNPs, corroborated by confocal microscopy and flow cytometry analyses of macrophage phenotypes. The in vivo assessments indicated that Ag@ADMH minimized fibrous capsule formation. In a full-thickness skin defect model of MRSA infection, the formulation significantly attenuated the inflammatory response by reducing MPO and CD68 expression levels, concurrently promoting collagen synthesis and CD34 expression, pivotal for vasculogenesis, thereby accelerating the resolution of MRSA-infected wounds. These attributes underscore the injectable extracellular matrix hydrogel as a formidable strategy for the remediation and regeneration of infected wounds. Graphical Abstract
研究领域:
生物材料学
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组织工程
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再生医学
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产品关联
DOI
PubMed
高影响因子
Applied Materials Today
·
2022
·
IF 8.663
Pengpeng Deng,Xiao Liang,Feixiang Chen,Yun Chen,Jinping Zhou
Wound healing is a complex dynamic process involving hemostasis, inflammation, proliferation and remodeling stages. It is urgent need to develop multifunctional hydrogels to treat multiple links of wound healing. In this work, we designed novel multifunctional dual-dynamic-bonds crosslinked hydrogels through the electrostatic interaction between phenylboric acid and the amino group of chitosan, and the dynamic borate ester bond between phenylboric acid and the catechol structure of PDA-modified CNTs. This dual dynamic cross-linking mechanism endowed hydrogels with very fast self-healing properties, which could quickly form a whole dressing after being injected into the wound site. The phenylboric acid and catechol structures endowed hydrogels with excellent adhesion properties, the adhesion strength to pig skin was up to 27.6 kPa, could be used for hemostasis in vivo . Moreover, hydrogels displayed the advantages of injectable, rapid shape adaptation, antioxidant, biocompatibility, blood compatibility, electrical conductivity and photothermal antibacterial properties. In the MRSA-infected wound model, hydrogels could effectively reduce the expression level of wound inflammatory factors, accelerate collagen deposition, epithelial tissue and vascular regeneration, and thus promote wound healing. This work provides a new idea for the design of multi-strategy therapy for wound healing and has broad clinical application prospects.
研究领域:
生物材料学
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医学
·
药剂学
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产品关联
DOI
高影响因子
Nano Today
·
2024
·
IF 13.2
Cong Wang,Chaofeng Wang,Shuilin Wu,Zhenduo Cui,Yufeng Zheng,Zhaoyang Li,Hui Jiang,Yu Zhang,Paul K. Chu,Shengli Zhu,Xiangmei Liu
Deep-seated osteomyelitis caused by bacterial infection, particularly methicillin-resistant Staphylococcus aureus (MRSA) infection, poses a significant challenge to treatment. In this study, we propose the utilization of a composite microwave (MW)-responsive polypyrrole-modified titanium carbide/zinc oxide (Ti 3 C 2 T x /ZnO–PPy) heterostructure as a potential therapeutic option for MRSA-infected osteomyelitis. In vitro and in vivo experiments show that Ti 3 C 2 T x /ZnO–PPy can effectively treat MRSA-induced osteomyelitis under MW irradiation, which is attributed to the enhanced in situ release of MW heat and reactive oxygen species (ROS). Density functional theory and MW network vector analysis further reveal that under MW irradiation, Ti 3 C 2 T x /ZnO–PPy generates free electrons that move freely within the heterogeneous interface formed by Ti 3 C 2 T x and ZnO, thereby enhancing the accumulation of charges. These charges combine with adsorbed oxygen at the interface to produce ROS. Furthermore, augmented dipole polarization induced by the functional groups on the surface of Ti 3 C 2 T x and the interfacial polarization between Ti 3 C 2 T x and ZnO contribute to good impedance matching and a favourable attenuation constant in the Ti 3 C 2 T x /ZnO–PPy composite, resulting in superior MW thermal properties. Moreover, the polypyrrole-modified composite shows excellent biocompatibility. This efficient antimicrobial system with MW irradiation is expected to offer a viable approach to the management of osteomyelitis.
研究领域:
微生物学
·
材料科学
·
医学
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产品关联
DOI
高影响因子
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