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JOURNAL OF NANOBIOTECHNOLOGY · 2024 ·Vol. 22 ·期 1 ·1-16 · IF 10.6

H2O2 self-supplying and GSH-depleting nanosystem for amplified NIR mediated-chemodynamic therapy of MRSA biofilm-associated infections

Zhao Yulan,Wu Yang,Xu Quan,Liu Yi,Song Zhiyong,Han Heyou

Reactive oxygen species (ROS) has emerged as potent therapeutic agents for biofilm-associated bacterial infections. Chemodynamic therapy (CDT), involving the generation of high-energy ROS, displays great potential in the therapy of bacterial infections. However, challenges such as insufficient hydrogen peroxide (H 2 O 2 ) and over-expressed glutathione (GSH) levels within the microenvironment of bacterial biofilms severely limit the antibacterial efficacy of CDT. Herein, we have developed a multifunctional nanoplatform (CuS@CaO 2 @Dex) by integrating copper sulfide (CuS) and calcium peroxide (CaO 2 ) into dextran (Dex)-coated nanoparticles. This innovative platform enhanced ROS generation for highly efficient biofilm elimination by simultaneously supplying H 2 O 2 and depleting GSH. The Dex-coating facilitated the penetrability of CuS@CaO 2 @Dex into biofilms, while CaO 2 generated a substantial amount of H 2 O 2 in the acidic biofilm microenvironment. CuS, through a Fenton-like reaction, catalyzed the conversion of self-supplied H 2 O 2 into hydroxyl radicals (•OH) and consumed the overexpressed GSH. Additionally, the incorporation of near-infrared II (NIR II) laser irradiation enhanced the photothermal properties of CuS, improving the catalytic efficiency of the Fenton-like reaction for enhanced antibacterial effects. In vivo experiments have demonstrated that CuS@CaO 2 @Dex exhibited remarkable antibacterial and antibiofilm efficacy, exceptional wound healing capabilities, and notable biosafety. In summary, the Dex-coated nanoplatform proposed in this study, with its self-sterilization capability through ROS, holds significant potential for future biomedical applications.

研究领域: 纳米技术 · 生物医学工程 · 药学 · 传染病学
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Nano Today · 2024 · IF 13.2

Microwave catalytic and thermal effects of Ti3C2Tx/ZnO–PPy enhanced by interfacial polarization for rapid treatment of MRSA-induced osteomyelitis

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.

CAS / MDL: 7789-24-4 109-97-7
研究领域: 微生物学 · 材料科学 · 医学
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Current Drug Delivery · 2024 · IF 2.8

Myristic Acid Solid Lipid Nanoparticles Enhance the Oral Bioavailability and Therapeutic Efficacy of Rifaximin against MRSA Pneumonia

Zhang Yumin,zhang Aoxue,Chen Dongmei,Xie Shuyu

Background: Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia is one of the leading causes of death and an immense financial burden on healthcare systems. Rifaximin (RFX) has good antibacterial activity against MRSA, but its clinical application is limited due to its poor oral absorption. Solid lipid nanoparticles have good biocompatibility, high drug loading, sustained release performance, and the inertia of lipids in gastric acid, which facilitates oral drug delivery. Objective: In order to improve the oral bioavailability of rifaximin and expand the clinical application of RFX for MRSA pneumonia, this study developed RFX-loaded myristic acid solid lipid nanoparticles (RFX-SLNs). Methods: This study first prepared RFX-SLNs through hot melt emulsification and ultrasonic methods and selected the optimal formula of RFX-SLNs through single-factor screening. Afterward, the particle size, zeta potential, and polydispersity index (PDI) of the RFX-SLNs were measured, the morphology of RFX-SLNs was observed by transmission electron microscopy, and the encapsulation efficiency (EE) and drug loading capacity (LC) of RFX-SLNs were detected by high-performance liquid chromatography. Then, the sustained release ability and oral bioavailability of RFX-SLNs were studied through in vitro release and pharmacokinetics. Finally, the therapeutic effect of RFX-SLNs on MRSA pneumonia infection was studied by using a mouse MRSA pneumonia infection model. Results: The optimal formulation of RFX-SLNs was 1% RFX with water (3% PVA) and oil (myristic acid) ratio of 1:19. RFX-SLNs were spherical in shape with a smooth surface and uniform size. The EE and LC of three different batches of RFX-SLNs were 89.35±2.47%, 90.45±3.69%, 88.72±1.18%, and 9.50 ± 0.01%, 10.09±0.01%, and 9.68±0.00%, respectively. In vitro release and pharmacokinetic studies showed that the myristic acid solid lipid nanoparticles showed excellent sustained release as expected and increased the oral bioavailability of RFX by 2.18 times. This indicates that RFX-SLNs can be used for the oral treatment of bacterial infections. Compared to RFX, RFX-SLNs showed good therapeutic effects in a mouse MRSA pneumonia infection model. Conclusion: This study indicates that the myristic acid solid lipid nanoparticles might be an effective way to enhance the oral absorption and therapy effects of RFX and other insoluble drugs. This not only opens up avenues for the clinical application of RFX but also provides a way for the development of new dosage forms of water-soluble drugs and the expansion of their clinical application scope.

研究领域: 药剂学 · 感染病学 · 纳米医学
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ACS Applied Materials & Interfaces · 2023 · IF 9.5

Thermosensitive Nanotherapeutics for Localized Photothermal Ablation of MRSA-Infected Osteomyelitis Combined with Chemotherapy

Zhe Zhao,Yufei Zhang,Yijie Cheng,Jie Li,Wenbo Wang,Siyuan Huang,Xinlong Ma,Xinge Zhang

Chronic osteomyelitis is an inflammatory skeletal disease caused by a bacterial infection that affects the periosteum, bone, and bone marrow. Methicillin-resistant Staphylococcus aureus (MRSA) is the most common causative agent. The bacterial biofilm formed on the necrotic bone is a considerable challenge to treating MRSA-infected osteomyelitis. Here, we developed an all-in-one cationic thermosensitive nanotherapeutic (TLCA) for treating MRSA-infected osteomyelitis. The prepared TLCA particles were positively charged and <230 nm in size, which allowed them to diffuse effectively into the biofilm. The positive charges of the nanotherapeutic accurately targeted the biofilm, and it subsequently regulated the drug release under near-infrared (NIR) light irradiation, thereby efficiently exerting the synergistic effect of NIR light-driven photothermal sterilization and chemotherapy. More than 80% of the antibiotics were abruptly released at 50 °C, which dispersed the biofilm by up to 90%. When applied to MRSA-infected osteomyelitis, with a localized temperature of 50 °C induced by 808 nm laser irradiation, it not only eliminated the bacteria and controlled infection but also inhibited the bone tissue inflammatory response, significantly reducing TNF-α, IL-1β, and IL-6 levels. In conclusion, we constructed an all-in-one antimicrobial treatment modality that provides a new and effective strategy for the topical treatment of chronic osteomyelitis.

CAS / MDL: 86393-32-0
研究领域: 纳米技术 · 药剂学 · 传染病学 · 生物医学工程
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Materials Today Bio · 2023 · IF 8.2

Microenvironment-responsive Cu-phenolic networks coated nanofibrous dressing with timely macrophage phenotype transition for chronic MRSA infected wound healing

Tianhua Xiao,Jiamin Liu,Yuanxin Li,Yu Cai,Xudan Xing,Ming Shao,Chi Zhang,Dongming Duan,Song Liu,Guoxin Tan,Le Wang,Zenghui Wu,Zunlei Gong,Lei Zhou

Methicillin-resistant Staphylococcus aureus (MRSA) infection is a pressing clinical issue that impedes wound healing. Pro-inflammatory M1 macrophages is required to clear bacteria and recruit various cell types during the initial phase of wound healing, but timing of this process is crucial. Herein, a microenvironment-responsive nanofibrous dressing capable of timely macrophage phenotype transition in vivo is constructed by coating copper ions (Cu 2+ )-polydopamine (PDA) networks on poly (ε-caprolactone) fiber (PCL-fiber) membrane. During the initial post-implantation period, the nanofibrous dressing show pH-sensitive Cu 2+ release in the acidic infection microenvironment. The release Cu 2+ have a direct killing effect on MRSA, and promote the proinflammatory M1 phenotype of macrophages to enhance the antibacterial macrophage response. Later, PDA to become a reactive oxygen species (ROS) scavenger when in microenvironments with elevated ROS levels, which conferred the dressing with an immunomodulatory activity that convert M1 macrophages into M2 macrophages. In vivo examination in an MRSA infected full-thickness skin wounds of rat model demonstrates that this dressing significantly facilitated infection eradication and wound healing through modulating local inflammatory phenotype. Overall, this study offers a simple and effective approach for timely manipulation of inflammation progression to promote infected wound healing.

研究领域: 生物医学工程 · 免疫学 · 材料科学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2022 · IF 6.51

Antibacterial activity of lysozyme-loaded cream against MRSA and promotion of scalded wound healing

Liang-Liang Chen,Wen-Pu Shi,Tuo-Di Zhang,Ya-Qing Zhou,Feng-Zhu Zhao,Wan-Yi Ge,Xiao-Qian Jin,Wen-Juan Lin,Wei-Hong Guo,Da-Chuan Yin

Staphylococcus aureus ( S. aureus ) infection, especially its drug-resistant bacterial infection, is a great challenge often faced by clinicians and patients, and it is also one of the most important threats to public health. Finding a safe and effective antibacterial agent is of great significance for the prevention and treatment of S. aureus infection. Lysozyme is known to have antibacterial effects against Gram-positive bacteria including S. aureus . Here, high-quality lysozyme with a purity of more than 99% and an activity of more than 60, 000 U/mg was prepared from egg white, which showed excellent antibacterial activity against three strains of S. aureus , especially against MRSA . Furthermore, an antibacterial cream loaded with lysozyme was prepared and tested in scald wound healing. The lysozyme-loaded cream exhibited the effect of preventing wound infection and promoting wound healing on scalds, and no toxicity was found in animal organs. Overall, lysozyme showed great application potential in the prevention and treatment of infections caused by S. aureus and scalded wound healing. The most remarkable discovery in this work is the unexpectedly powerful inhibitory effect of lysozyme on the drug-resistant bacterial, especially MRSA , which is usually very difficult to deal with using normal antibacterial drugs.

CAS / MDL: 8009-03-8 112-92-5
研究领域: 药学 · 微生物学 · 伤口愈合 · 传染病学
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Bioactive Materials · 2025 · IF 20.3

NIR-II-Activated iridium single-atom nanozymes for synergistic antibacterial therapy and tissue regeneration in MRSA-infected wounds and acute lung injury

Danyan Wang,Hui Jin,Yetao Shen,Dandan Wang,Jingjing He,Jinmiao Qu,Xiaojun He,Zhengli Jiang

Methicillin-resistant Staphylococcus aureus (MRSA) remains a major pathogen in ventilator-associated pneumonia and wound infections. To address the limitations of traditional antibiotics, we developed a novel iridium-based single-atom catalyst (Ir/CN SAC) anchored on a nitrogen-doped carbon matrix. Engineered for ultra-low metal loading and maximal active site exposure, this catalyst integrates robust photothermal and catalytic functionalities. Under second near-infrared (NIR-II, 1270 nm) irradiation, the Ir/CN SAC efficiently converts light to heat and catalytically generates reactive oxygen species (ROS), achieving a potent photothermal-catalytic synergistic effect. This dual-action mechanism enabled rapid bacterial eradication in vitro and significantly accelerated wound healing and lung tissue repair in MRSA-infected in vivo models. Transcriptomic analyses revealed downregulation of pro-inflammatory pathways, shedding light on the immunomodulatory roles of the treatment. Notably, the Ir/CN SAC exhibited negligible toxicity and enhanced peroxidase-mimicking activity via thermal activation. Collectively, the Ir/CN SAC presents a promising strategy for treating MRSA infections in wounds and the lungs via a synergistic treatment model.

CAS / MDL: 54827-17-7
研究领域: 生物医学工程 · 纳米医学 · 感染病学
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CHEMICAL ENGINEERING JOURNAL · 2024 · IF 13.3

In situ formed antibacterial hydrogel with collagenase-responsive activity for prevention of MRSA-induced osteomyelitis

Kejia Li,Xiaoyan Ju,Xiangli Li,Guojun Lu,Jinzhao Ou,Dandan Xu,Chenxiao Wan,Meng Zhu,Chuanchao Du,Ye Tian,Zhongwei Niu

Osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) is a challenging and life-threatening disease due to its long duration and deep site of occurrence. Herein, we design an in situ formed antibacterial hydrogel with collagenase-respontive activity for the prevention of MRSA-induced osteomyelitis. This hydrogel is constructed by chemical bonding between a 4-arm polyethylene glycol maleimide (4-Arm-PEG-Mal), an N-terminal maleimidated antimicrobial peptide (Mal-AMP) and a collagenase-cleavable peptide with two thiol groups (HS-VPM-SH). Collagenase-induced hydrogel cleavage confers on-demand delivery of the antimicrobial peptide, thereby enhancing the combating activity against MRSA in an infected environment. The designed hydrogel, namely AMP/VPM/PEG hydrogel, can be formed rapidly in situ under physiological conditions due to the rapid bonding between the maleimide and thiol groups. In the in vivo rat osteomyelitis model, the AMP/VPM/PEG hydrogel can be administered by simply injecting the 4-Arm-PEG-Mal and peptide solutions with a 26G needle, which is a minimally invasive method. In vivo evaluation further demonstrates that AMP/VPM/PEG hydrogel can successfully prevent MRSA-induced osteomyelitis. This work provides a minimally invasive approach for intramedullary delivery of antimicrobial peptides on-demand and may provide a viable strategy for the osteomyelitis prevention in clinic.

研究领域: 生物医学工程 · 药学 · 传染病学 · 材料科学
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ACS Applied Materials & Interfaces · 2025 · IF 8.2

Spindle-Shaped Multifunctional Nanozymes with NIR-Enhanced Catalytic Activity for Treating Methicillin-Resistant Staphylococcus aureus (MRSA)-Infected Wounds through Bacterial Cuproptosis-like Death

Chongqing Yu,Qiqi Lu,Yichun Wang,Zujiang Liu,Sathishkumar Gnanasekar,Ugo D’Amora,En-Tang Kang,Liqun Xu,Jie Xu,Xi Rao

Methicillin-resistant Staphylococcus aureus (MRSA) wound infections remain a significant global challenge and demand new-generation biomaterials to eliminate bacterial infections and promote rapid wound healing. Although the nanozyme is a promising approach, the restricted unimodal bactericidal functionality hinders its efficacy in treating complex wound infections. In this study, copper-tannic acid (Cu-TA) nanozymes (NMs) with multifunctional properties were developed for the treatment of bacterial infections and biofilms via cuproptosis-like cell death. The as-prepared Cu-TA demonstrated peroxidase-like (POD-like) activity, generating substantial amounts of hydroxyl radicals (•OH). In vitro studies revealed that Cu-TA efficiently disrupted bacterial biofilms, while in vivo experiments demonstrated its ability to promote anti-inflammatory responses, angiogenesis, collagen synthesis, and cellular proliferation. Transcriptome sequencing revealed that bacterial reactive oxygen species (ROS) caused damage to the cell membrane and disrupted metabolic processes. Furthermore, copper overload triggered lipid peroxidation (LPO) buildup and interfered with the tricarboxylic acid (TCA) cycle, culminating in cuproptosis-like bacterial death. Overall, this study successfully developed a spindle-shaped, multifunctional nanozyme for combating bacterial infections through cuproptosis-like cell death while promoting infected wound healing. The results validate the clinical potential of Cu-TA NMs for treating MRSA-infected wounds.

CAS / MDL: 1401-55-4 9002-18-0
研究领域: 生物材料学 · 纳米医学 · 感染与免疫 · 分子生物学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Mussel-inspired near-infrared light-responsive gelatin-based hydrogels for enhancing MRSA-infected wound healing

Jian Yang,Haojie Yu,Li Wang,Xiaowei Liu,Yudi Huang,Yichuan Hong,Shuning Ren

Infected wound management is a great challenge to healthcare, especially in emergencies such as accidents or battlefields. Hydrogels as wound dressings can replace or supplement traditional wound treatment strategies, such as bandages or sutures. It is significant to develop novel hydrogel-based wound dressings with simple operation, inexpensive, easy debridement, effective antibacterial, biocompatibility, etc. Here, we designed a novel gelatin-based hydrogel wound dressing Gel-TA-Fe 3+ . The hydrogels used tannic-modified gelatin as the main body and Fe 3+ as the crosslinking agent to achieve a controllable rapid sol-gel transition. The hydrogels exhibited tough mechanical properties, excellent antibacterial ability, biocompatibility and an acceptable temperature response to near-infrared light (NIR). Moreover, the hydrogels could promote the healing process of MRSA -infected skin wound in rats. This multifunctional hydrogel was thought to have potential for emergency treatment of bacterial infected wound.

CAS / MDL: 10025-77-1 70-51-9
研究领域: 材料科学 · 生物医学工程 · 伤口愈合 · 抗菌治疗 · 生物材料
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CARBOHYDRATE POLYMERS · 2024 · IF 10.7

Quaternary ammonium chitosan-functionalized mesoporous silica nanoparticles: A promising targeted drug delivery system for the treatment of intracellular MRSA infection

Junfeng Liu,Liying Zhang,Haodi Ma,Haoyang Sun,Shu-ai Ge,Jieyi Liu,Shengdi Fan,Chunshan Quan

The limited membrane permeability and bacterial resistance pose significant challenges in the management of intracellular drug-resistant bacterial infections. To overcome this issue, we developed a bacterial-targeted drug delivery system based on quaternary ammonium chitosan-modified mesoporous silica nanoparticles (MSN-NH 2 -CFP@HACC) for the treatment of intracellular Methicillin-resistant Staphylococcus aureus (MRSA) infections. This system utilizes amino-functionalized mesoporous silica nanoparticles to efficiently load cefoperazone (CFP), and the nanoparticles' surface is coated with 2-hydroxypropyltrimethyl ammonium chloride chitosan (HACC) to target bacteria and enhance macrophage uptake. The findings indicate that MSN-NH 2 -CFP@HACC nanoparticles are efficiently internalized by macrophages, demonstrate accelerated drug release in acidic environments, and exhibit enhanced antibacterial properties, effectively suppressing the proliferation and intracellular escape of MRSA. Moreover, HACC enhances the bacterial capture ability of the nanoparticles and reduces resistance by disrupting bacterial membrane structures and inhibiting bacterial β-lactamase activity. In a murine model of MRSA bacteremia, MSN-NH 2 -CFP@HACC exhibited remarkable antibacterial efficacy and significantly attenuated severe inflammatory responses. In conclusion, MSN-NH 2 -CFP@HACC represent a promising antibiotic delivery system with exceptional antibacterial efficacy and favorable biocompatibility, thus presenting a novel strategy for addressing intracellular drug-resistant bacterial infections and demonstrating significant potential for clinical application.

研究领域: 药理学 · 纳米医学 · 微生物学
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INTERNATIONAL JOURNAL OF PHARMACEUTICS · 2024 · IF 5.3

Enhancing transdermal delivery of chrysomycin A for the treatment of cutaneous melanoma and MRSA infections using Skin-Penetrating Peptide-Functionalized deformable liposomes

Yue Cai,Xinrui Zhang,Wentao Hu,Fuhang Song,Hong Wang,Huawei Zhang,Xuanrong Sun

Transdermal drug delivery represents a promising avenue for the treatment of dermatologic diseases, such as cutaneous melanoma and skin infections. This study involves the development of a novel therapeutic strategy that employs a skin-penetrating peptide SPACE-modified flexible liposomal chrysomycin A (CA@SPACE-LP) with a particle size of 111.5 nm. In vitro transdermal experiments demonstrated that CA@SPACE-LP was effective in enhancing the ability of the drug to penetrate the stratum corneum and enter deep into the skin tissue, increasing the intradermal drug concentration up to threefold compared to free CA. Furthermore, CA@SPACE-LP was observed to maintain the biological activity of CA against planktonic Methicillin-resistant Staphylococcus aureus (MRSA) and melanoma cells. In vivo studies demonstrated that the topical administration of CA@SPACE-LP was efficacious in controlling the progression of cutaneous melanoma, with a tumor suppression rate of approximately 60 %, which was more pronounced than that observed with intravenous Taxol. Furthermore, CA@SPACE-LP demonstrated efficacy in the management of intradermal MRSA infections, with a significantly reduced area of ulceration in the treated mice (0.25 cm 2 ) compared to the positive control drug (Mupirocin Ointment). These results suggest that the topical delivery system developed in this study has the potential to be used for the simultaneous treatment of skin cancer and invasive MRSA infection.

研究领域: 药剂学 · 皮肤病学 · 肿瘤学 · 微生物学
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