RESUMEN
Bacteria infections pose a serious threat to public health, and it is urgent to develop facile and accurate detection methods. To meet the important need, a potable and high-sensitive surface enhanced Raman scattering (SERS) biosensor based on aptamer recognition and catalytic hairpin assembly (CHA) signal amplification was proposed for point-of-care detection of Staphylococcus aureus (S. aureus). The SERS biosensor contains three parts: recognition probes, SERS sensing chip, and SERS tags. The feasibility of the strategy was verified by gel electrophoresis, and the one-step test route was optimized. The bacteria SERS biosensor has a good linear relationship ranging from 10 to 107 CFU mL-1 with high sensitivity low to 5 CFU mL-1, and shows excellent specificity, uniformity, and repeatability on S. aureus identification and enumeration, which can distinguish S. aureus from other bacteria. The SERS biosensor shows a good recovery rate (95.73 %-109.65 %) for testing S. aureus spiked in milk, and has good practicability for detecting S. aureus infected mouse wound, which provides a facile and reliable approach for detection of trace bacteria in the real samples.
Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Espectrometría Raman , Staphylococcus aureus , Staphylococcus aureus/aislamiento & purificación , Técnicas Biosensibles/métodos , Aptámeros de Nucleótidos/química , Espectrometría Raman/métodos , Animales , Leche/microbiología , Leche/química , Límite de Detección , Ratones , Nanopartículas del Metal/química , Catálisis , Oro/química , Infecciones Estafilocócicas/diagnóstico , Infecciones Estafilocócicas/microbiologíaRESUMEN
Catalytic therapy based on nanozymes is promising for the treatment of bacterial infections. However, its therapeutic efficacy is usually restricted by the limited amount of hydrogen peroxide and the weak acidic environment in infected tissues. To solve these issues, we prepared polyvinyl alcohol (PVA)-polyacrylic acid (PAA)-iron oxide (Fe3O4)/polyvinyl alcohol (PVA)-zinc peroxide (ZnO2) double-layer electrospun nanofibers (PPF/PZ NFs). In this design, PVA serves as the carrier for ZnO2 nanoparticles (NPs), Fe3O4 NPs, and PAA. The double-layer structure of nanofibers can spatially separate the PAA and ZnO2 to avoid their reaction with each other during preparation and storage, while in the wet wound bed, PVA can dissolve and PAA can provide H+ ions to promote the generation of hydrogen peroxide and subsequent conversion to hydroxyl radicals for bacteria killing. In vitro experimental results demonstrated that PPF/PZ NFs can reduce the methicillin-resistant Staphylococcus aureus by 3.1 log (99.92%). Moreover, PPF/PZ NFs can efficiently treat the bacterial infection in a mouse wound model and promote wound healing with negligible toxicity to animals, indicating their potential use as "plug-and-play" antibacterial wound dressings. This work provides a novel strategy for the construction of double-layer electrospun nanofibers as catalytic wound dressings with hydrogen peroxide/acid self-supplying properties for the efficient treatment of bacterial infections.
Asunto(s)
Antibacterianos , Peróxido de Hidrógeno , Staphylococcus aureus Resistente a Meticilina , Nanofibras , Infección de Heridas , Óxido de Zinc , Nanofibras/química , Animales , Ratones , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/farmacología , Catálisis , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Antibacterianos/química , Antibacterianos/farmacología , Infección de Heridas/tratamiento farmacológico , Óxido de Zinc/química , Óxido de Zinc/farmacología , Alcohol Polivinílico/química , Resinas Acrílicas/química , Resinas Acrílicas/farmacología , Cicatrización de Heridas/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/tratamiento farmacológico , Tamaño de la PartículaRESUMEN
Implant infections are severe complications in clinical treatment, which often accompany the formation of bacterial biofilms with high antibiotic resistance. Sonodynamic therapy (SDT) is an antibiotic-free method that can generate reactive oxygen species (ROS) to kill bacteria under ultrasound (US) treatment. However, the extracellular polymeric substances (EPS) barrier of bacterial biofilms and the hypoxic microenvironment significantly limit the antibiofilm activity of SDT. In this study, lipid-shelled perfluoropentane (PFP) nanodroplets loaded with gallium protoporphyrin IX (GaPPIX) and oxygen (O2) (LPGO NDs) were developed for the treatment of implant infections. Under US stimulation, LPGO NDs undergo the cavitation effect and disrupt the biofilm structure like bombs due to liquid-gas phase transition. Meanwhile, the LPGO NDs release O2 and GaPPIX upon US stimulation. The released O2 can alleviate the hypoxic microenvironment in the biofilm and enhance the ROS formation by GaPPIX for enhanced bacterial killing. In vivo experimental results demonstrate that the LPGO NDs can efficiently treat implant infections of methicillin-resistant Staphylococcus aureus (MRSA) in a mouse model by disrupting the biofilm structure, alleviating hypoxia, and enhancing bacterial killing by SDT. Therefore, this work provides a new multifunctional sonosensitizer to overcome the limitations of SDT for treating implant infections.
Asunto(s)
Biopelículas , Fluorocarburos , Galio , Staphylococcus aureus Resistente a Meticilina , Oxígeno , Protoporfirinas , Infecciones Estafilocócicas , Terapia por Ultrasonido , Animales , Fluorocarburos/química , Fluorocarburos/farmacología , Ratones , Galio/química , Galio/farmacología , Protoporfirinas/química , Protoporfirinas/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Biopelículas/efectos de los fármacos , Oxígeno/química , Infecciones Estafilocócicas/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Nanopartículas/química , Antibacterianos/farmacología , Antibacterianos/química , Ratones Endogámicos BALB C , Femenino , PentanosRESUMEN
The Pseudomonas aeruginosa biofilm in recalcitrant chronic lung infections not only develops high antimicrobial tolerance but also induces an aberrant host inflammatory response. The metabolic condition plays a vital role in both the antimicrobial susceptibility of bacteria and the inflammatory response of immune cells, thereby offering a potential therapeutic target. Herein, we described a metabolic modulation strategy by using ultrasound-responsive liposomal nanoparticles containing a sonosensitizer and a hypoxia-activated prodrug against biofilm-associated chronic lung infections. Under ultrasound stimulation, the sonosensitizer generates antibacterial reactive oxygen species by oxygen consumption. Subsequently, the oxygen consumption-mediated hypoxia not only induces the anaerobic metabolism of bacteria for antibiotic activation but also triggers the glycolysis pathway of immune cells for inflammatory activation. Such metabolic modulation strategy demonstrated efficient therapeutic efficacy for P. aeruginosa biofilm-induced chronic lung infections in mice models and provides a promising way for combating biofilm-associated chronic infections.
Asunto(s)
Antibacterianos , Biopelículas , Infecciones por Pseudomonas , Pseudomonas aeruginosa , Animales , Antibacterianos/farmacología , Antibacterianos/química , Pseudomonas aeruginosa/efectos de los fármacos , Ratones , Biopelículas/efectos de los fármacos , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/inmunología , Nanopartículas/química , Liposomas/química , Enfermedad Crónica , Especies Reactivas de Oxígeno/metabolismo , Profármacos/farmacología , Profármacos/químicaRESUMEN
Foodborne pathogens are harmful to human health because they can contaminate food and induce diseases. To efficiently distinguish and determine foodborne bacteria, an ultrasensitive point-of-care electrochemical biosensor was designed for 16S rRNA detection by coupling a signal amplification strategy with MoS2-based nanoprobes. Gold nanoparticles and thionine co-functionalized molybdenum disulfide (MoS2) nanocomposites (MoS2-Thi-AuNPs) were used to construct nanoprobes, which can efficiently monitor the detection process and amplify the detection signal. In the presence of Escherichia coli (E. coli) 16S rRNA, a classical sandwiched DNA structure was formed on the surface of a hierarchical flower-like gold nanostructure-decorated screen-printed carbon electrode (HFGN-SPCE), generating an obvious electrochemical signal from Thi. Under optimal conditions, this designed electrochemical biosensor showed a wide dynamic range (0-1.0 × 106 fM), low detection limit (2.8 fM), high selectivity and accepted stability for E. coli 16S rRNA detection in ideal buffers. Moreover, this biosensor can efficiently determine 16S rRNA in milk samples and 10 CFU mL-1 bacterial lysate. All experimental results suggested that this biosensor has a promising application in the detection of foodborne pathogens.
Asunto(s)
Técnicas Biosensibles , Nanopartículas del Metal , Nanocompuestos , Humanos , Escherichia coli/genética , ARN Ribosómico 16S/genética , Oro/química , Nanopartículas del Metal/química , Molibdeno/química , Sistemas de Atención de Punto , Técnicas Electroquímicas/métodos , Técnicas Biosensibles/métodos , Nanocompuestos/química , Límite de DetecciónRESUMEN
Virus-related infectious diseases are serious threats to humans, which makes virus detection of great importance. Traditional virus-detection methods usually suffer from low sensitivity and specificity, are time-consuming, have a high cost, etc. Recently, DNA biosensors based on DNA nanotechnology have shown great potential in virus detection. DNA nanotechnology, specifically DNA tiles and DNA aptamers, has achieved atomic precision in nanostructure construction. Exploiting the programmable nature of DNA nanostructures, researchers have developed DNA nanobiosensors that outperform traditional virus-detection methods. This paper reviews the history of DNA tiles and DNA aptamers, and it briefly describes the Baltimore classification of virology. Moreover, the advance of virus detection by using DNA nanobiosensors is discussed in detail and compared with traditional virus-detection methods. Finally, challenges faced by DNA nanobiosensors in virus detection are summarized, and a perspective on the future development of DNA nanobiosensors in virus detection is also provided.
Asunto(s)
Aptámeros de Nucleótidos , Nanoestructuras , Humanos , Nanotecnología , ADNRESUMEN
The advent of drug-resistant pathogens results in the occurrence of stubborn bacterial infections that cannot be treated with traditional antibiotics. Antibacterial immunotherapy by reviving or activating the body's immune system to eliminate pathogenic bacteria has confirmed promising therapeutic strategies in controlling bacterial infections. Subsequent studies found that antimicrobial immunotherapy has its own benefits and limitations, such as avoiding recurrence of infection and autoimmunity-induced side effects. Current studies indicate that the various antibacterial therapeutic strategies inducing immune regulation can achieve superior therapeutic efficacy compared with monotherapy alone. Therefore, summarizing the recent advances in nanomedicine with immunomodulatory functions for combating bacterial infections is necessary. Herein, we briefly introduce the crisis caused by drug-resistant bacteria and the opportunity for antibacterial immunotherapy. Then, immune-involved multimodal antibacterial therapy for the treatment of infectious diseases was systematically summarized. Finally, the prospects and challenges of immune-involved combinational therapy are discussed.
RESUMEN
Dental diseases associated with biofilm infections and tooth staining affect billions of people worldwide. In this study, we combine photothermal agents (MoS2@BSA nanosheets, MB NSs), a thermolysis free-radical initiator (AIPH), and carbomer gel to develop laser-responsive hydrogel (MBA-CB Gel) for biofilm inactivating and tooth whitening. Under a physiological temperature without laser irradiation, MB NSs can eliminate free radicals generated from the slow decomposition of AIPH due to their antioxidative activity, thereby avoiding potential side effects. A cytotoxicity study indicates that MB NSs can protect mammalian cells from the free radicals released from AIPH without laser irradiation. Upon exposure to laser irradiation, MB NSs promote the rapid decomposition of AIPH to release free radicals by photothermal effect, suggesting their on-demand release ability of free radicals. In vitro experimental results show that the bacteria inactivation efficiency is 99.91% (3.01 log units) for planktonic Streptococcus mutans (S. mutans) and 99.98% (3.83 log units) for planktonic methicillin-resistant Staphylococcus aureus (MRSA) by the mixed solution of MB NSs and AIPH (MBA solution) under 808 nm laser irradiation (1.0 W/cm2, 5 min). For S. mutans biofilms, an MBA solution can inactivate 99.97% (3.63 log units) of the bacteria under similar laser irradiation conditions. Moreover, MBA-CB Gel can whiten an indigo carmine-stained tooth under laser irradiation after 60 min of laser treatment, and the color difference (ΔE) in the teeth of the MBA-CB Gel treatment group was 10.9 times that of the control group. This study demonstrates the potential of MBA-CB Gel as a promising platform for biofilm inactivation and tooth whitening. It is worth noting that, since this study only used stained models of extracted teeth, the research results may not fully reflect the actual clinic situation. Future clinical research needs to further validate these findings.
RESUMEN
The application of medical implants has greatly improved the survival rate and life quality of patients. Nevertheless, in recent years, there are increasing cases of implant dysfunction or failure because of bacterial infections. Despite significant improvements in biomedicine, there are still serious challenges in the treatment of implant-related infections. With the formation of bacterial biofilms and the development of bacterial resistance, these limitations lead to a low efficacy of conventional antibiotics. To address these challenges, it is urgent to exploit innovative treatment strategies for implant-related infections. Based on these ideas, environment-responsive therapeutic platforms with high selectivity, low drug resistance, and minor dose-limiting toxicity have attracted widespread attention. By using exogenous/endogenous stimuli, the antibacterial activity of therapeutics can be activated on demand and exhibit remarkable therapeutic effects. Exogenous stimuli include photo, magnetism, microwave, and ultrasound. Endogenous stimuli mainly include the pathological characteristics of bacterial infections such as acidic pH, anomalous temperature, and abnormal enzymatic activities. In this review, the recent progress of environment-responsive therapeutic platforms with spatiotemporally controlled drug release/activation is systematically summarized. Afterward, the limitations and opportunities of these emerging platforms are highlighted. Finally, it is hoped that this review will offer novel ideas and techniques to combat implant-related infections.
Asunto(s)
Infecciones Bacterianas , Biopelículas , Humanos , Sistemas de Liberación de Medicamentos , Infecciones Bacterianas/tratamiento farmacológico , Bacterias , Prótesis e Implantes , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
Implant infections are difficult to cure by traditional antibiotic therapy due to bacterial biofilm-induced antibiotic tolerance and impaired immune responses. To efficiently treat implant infections, therapeutic agents need to kill bacteria and regulate the inflammatory response of immune cells during the biofilm elimination process. Herein, multifunctional smart hollow Cu2MoS4 nanospheres (H-CMS NSs) with pH-responsive enzyme-like activities were prepared for self-adaptively eliminating biofilms and regulating the inflammation of macrophages in implant infections. During biofilm infection, the tissue microenvironment around implants is acidic. H-CMS NSs with oxidase (OXD)/peroxidase (POD)-like activities can catalyze reactive oxidative species (ROS) generation for directly killing bacteria and polarizing macrophages to a proinflammatory phenotype. Moreover, the POD-like activity and antibacterial property of H-CMS NSs can be further enhanced under ultrasound (US) irradiation. After the elimination of biofilms, the tissue microenvironment around implants shifts from acidic to neutral. H-CMS NSs show catalase (CAT)-like activity and eliminate excessive ROS, which polarizes macrophages to anti-inflammatory phenotype and promotes healing of infected tissue. This work provides a smart nanozyme with self-adaptive regulation of the antibiofilm activity and immune response by regulating ROS generation/elimination according to the different pathological microenvironments in implant infections during the different therapeutic stages.
Asunto(s)
Nanosferas , Humanos , Especies Reactivas de Oxígeno/farmacología , Biopelículas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Complicaciones Posoperatorias , BacteriasRESUMEN
Traditional dendritic cell (DC)-mediated immunotherapy is usually suppressed by weak immunogenicity in tumors and generally leads to unsatisfactory outcomes. Synergistic exogenous/endogenous immunogenic activation can provide an alternative strategy for evoking a robust immune response by promoting DC activation. Herein, Ti3 C2 MXene-based nanoplatforms (termed MXP) are prepared with high-efficiency near-infrared photothermal conversion and immunocompetent loading capacity to form endogenous/exogenous nanovaccines. Specifically, the immunogenic cell death of tumor cells induced by the photothermal effects of the MXP can generate endogenous danger signals and antigens release to boost vaccination for DC maturation and antigen cross-presentation. In addition, MXP can deliver model antigen ovalbumin (OVA) and agonists (CpG-ODN) as an exogenous nanovaccine (MXP@OC), which further enhances DC activation. Importantly, the synergistic strategy of photothermal therapy and DC-mediated immunotherapy by MXP significantly eradicates tumors and enhances adaptive immunity. Hence, the present work provides a two-pronged strategy for improving immunogenicity and killing tumor cells to achieve a favorable outcome in tumor patients.
Asunto(s)
Vacunas contra el Cáncer , Nanopartículas , Neoplasias , Humanos , Neoplasias/terapia , Presentación de Antígeno , Antígenos/farmacología , Inmunoterapia , Células Dendríticas , Vacunas contra el Cáncer/farmacologíaRESUMEN
Efficient treatment of chronic lung infections caused by Pseudomonas aeruginosa biofilms is a great challenge because of drug tolerance and immune evasion issues. Here, we develop ultrasound-responsive catalytic microbubbles with biofilm elimination and immune activation properties to combat chronic lung infection induced by P. aeruginosa biofilms. In these microbubbles, piperacillin and Fe3O4 nanoparticles form a drug-loaded shell surrounding the air core. Under ultrasound stimulation, the microbubbles can physically disrupt the structure of biofilms and enhance the penetration of both Fe3O4 nanoparticles and piperacillin into the biofilm. Then, Fe3O4 nanoparticles chemically degrade the biofilm matrix and kill the bacteria with the assistance of piperacillin. Fe3O4 nanoparticles can activate the immune response for biofilm elimination by polarizing macrophages into a pro-inflammatory phenotype. These ultrasound-responsive catalytic microbubbles efficiently treat chronic lung infections in a mouse model by combining physical/chemical/antibiotic biofilm elimination and immune activation, thus providing a promising strategy for combating bacterial biofilm infections.
Asunto(s)
Infecciones Bacterianas , Microburbujas , Animales , Ratones , Biopelículas , Antibacterianos/farmacología , Piperacilina/metabolismo , Pulmón , Pseudomonas aeruginosaRESUMEN
Effective treatment of bacterial biofilm-related infections is a great challenge for the medical community. During the formation of biofilms, bacteria excrete extracellular polymeric substances (EPS), including polysaccharides, proteins, nucleic acids, etc., to encapsulate themselves and form a "fort-like" structure, which greatly reduces the efficiency of therapeutic agents. Herein, we prepared a nanoagent (MnO2-amylase-PEG-ICG nanosheets, MAPI NSs) with biofilm degradation capability for efficient photothermal therapy and fluorescence imaging of methicillin-resistant Staphylococcus aureus (MRSA) biofilm infections. MAPI NSs were constructed by sequentially modifying α-amylase, polyethylene glycol (PEG), and indocyanine green (ICG) on manganese dioxide nanosheets (MnO2 NSs). Experimental results exhibited that MAPI NSs could accumulate in infected tissues after intravenous injection, degrade in the acidic biofilm microenvironment, and release the loaded ICG for near-infrared (NIR) fluorescence imaging of the infected tissues. Importantly, MAPI NSs could efficiently eliminate MRSA biofilm infections in mice by α-amylase enhanced photothermal therapy. In addition, MAPI NSs exhibited neglectable toxicity towards mice. Given the superior properties of MAPI NSs, the enzyme-degradation enhanced therapeutic strategy presented in this work offers a promising solution for effectively combating biofilm infectious diseases.
Asunto(s)
Infecciones Bacterianas , Staphylococcus aureus Resistente a Meticilina , Ratones , Animales , Terapia Fototérmica , Compuestos de Manganeso , Amilasas , Óxidos , Polietilenglicoles/química , Verde de Indocianina/química , Biopelículas , alfa-Amilasas , Imagen Óptica , Antibacterianos/farmacología , Antibacterianos/químicaRESUMEN
Two-dimensional (2D) transition metal dichalcogenide nanosheets (TMDC NSs) have attracted growing interest due to their unique structure and properties. Although various methods have been developed to prepare TMDC NSs, there is still a great need for a novel strategy combining simplicity, generality, and high efficiency. In this study, we developed a novel polymer-assisted ball milling method for the efficient preparation of TMDC NSs with small sizes. The use of polymers can enhance the interaction of milling balls and TMDC materials, facilitate the exfoliation process, and prevent the exfoliated nanosheets from aggregating. The WSe2 NSs prepared by carboxymethyl cellulose sodium (CMC)-assisted ball milling have small lateral sizes (8~40 nm) with a high yield (~60%). The influence of the experimental conditions (polymer, milling time, and rotation speed) on the size and yield of the nanosheets was studied. Moreover, the present approach is also effective in producing other TMDC NSs, such as MoS2, WS2, and MoSe2. This study demonstrates that polymer-assisted ball milling is a simple, general, and effective method for the preparation of small-sized TMDC NSs.
RESUMEN
Gold nanocubes (AuNCs) with tunable localized surface plasmon resonance properties are good candidates for plasmonic gap nanostructures (PGNs) with hot spots (areas with intense electric field localization). Nevertheless, it remains challenging to create shape-controllable nanogaps between AuNCs. Herein, we report a DNA origami directed pattern recognition strategy to assemble AuNCs into PGNs. By tuning the position and number of capture strands on the DNA origami template, different geometrical configurations of PGNs with nanometer-precise and shape-controllable gaps are created. The localized field enhancement in these gaps can generate hot spots that are in accordance with finite difference time domain simulations. Benefiting from the single Raman probe molecule precisely anchored at these nanogaps, the dramatic enhanced electromagnetic fields localized in hot spots arouse stronger single-molecule SERS (SM-SERS) signals. This method can be utilized in the design of ultrahigh-sensitivity photonic devices with tailored optical properties and SERS-based applications.
Asunto(s)
Nanopartículas del Metal , Nanoestructuras , ADN/química , Oro/química , Nanopartículas del Metal/química , Nanoestructuras/química , Espectrometría RamanRESUMEN
Diabetic wound infection is a common disease that has significantly reduced people's quality of life. Although tremendous achievements have been made in clinical treatment, the crucial challenge in diabetic infected wound management stems from the detrimental diabetic wound environment and the emergence of bacterial resistance after long-term medication, which result in a reduced efficacy, an increased dosage of medication, and severe side effects. To tackle these issues, it is of great significance to develop an innovative treatment strategy for diabetic wound infection therapy. Currently, the exploitation of nanobiomaterial-based therapeutic systems for diabetic infected wounds is booming, and therapeutic systems with a stimuli-responsive performance have received extensive attention. These therapeutic systems are able to accelerate diabetic infected wound healing due to the on-demand release of therapeutic agents in diabetic infected wounds in response to stimulating factors. Based on the characteristics of diabetic infected wounds, many endogenous stimuli-responsive (e.g., glucose, enzyme, hypoxia, and acidity) therapeutic systems have been employed for the targeted treatment of infected wounds in diabetic patients. Additionally, exogenous stimulants, including light, magnetism, and temperature, are also capable of achieving on-demand drug release and activation. In this review, the characteristics of diabetic infected wounds are presented, and then exogenous/endogenous stimuli therapeutic systems for the treatment of diabetic infected wounds are summarized. Finally, the current challenges and future outlook of stimuli-responsive therapeutic systems are also discussed.
Asunto(s)
Diabetes Mellitus , Pie Diabético , Infección de Heridas , Pie Diabético/tratamiento farmacológico , Glucosa/uso terapéutico , Humanos , Calidad de Vida , Cicatrización de Heridas , Infección de Heridas/tratamiento farmacológicoRESUMEN
Traditional antibiotic treatment has limited efficacy for the drug-tolerant bacteria present in biofilms because of their unique metabolic conditions in the biofilm infection microenvironment. Modulating the biofilm infection microenvironment may influence the metabolic state of the bacteria and provide alternative therapeutic routes. In this study, photodynamic therapy is used not only to eradicate methicillin-resistant Staphylococcus aureus biofilms in the normoxic condition, but also to potentiate the hypoxic microenvironment, which induces the anaerobic metabolism of methicillin-resistant Staphylococcus aureus and activates the antibacterial activity of metronidazole. Moreover, the photodynamic therapy-activated chemotherapy can polarize the macrophages to a M2-like phenotype and promote the repair of the biofilm infected wounds in mice. This biofilm infection microenvironment modulation strategy, whereby the hypoxic microenvironment is potentiated to synergize photodynamic therapy with chemotherapy, provides an alternative pathway for efficient treatment of biofilm-associated infections.
Asunto(s)
Infecciones Bacterianas , Staphylococcus aureus Resistente a Meticilina , Fotoquimioterapia , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Biopelículas , RatonesRESUMEN
The extensive usage of antibiotics causes the rapid evolution of drug-resistant bacteria, which seriously threaten human health. Thus, efficient strategies for treating drug-resistant bacterial infections are urgently needed. Herein, MoS2-Cu2WS4 nanosheets (MS-CWS NSs) are prepared as a near-infrared (NIR) light responsive nanozyme to effectively combat methicillin-resistant Staphylococcus aureus (MRSA) infections by catalytic/photothermal effects. By integrating oxidase (OXD)- and peroxidase (POD)-mimic catalytic activity, MS-CWS NSs have the ability to inactivate MRSA without the addition of H2O2. Moreover, the reactive oxygen species (ROS) produced from MS-CWS NSs are further enhanced by NIR light irradiation, which remarkably causes the death of MRSA. MS-CWS NSs show 4.4 log (99.996%) bacterial inactivation efficiency of MRSA in vitro under NIR light irradiation (0.8 W cm-2, 5 min). In an MRSA infected wound mouse model, MS-CWS NSs inactivate the MRSA by more than 5.2 log (>99.999%) and effectively promote wound healing. This work provides an NIR-responsive 2D nanozyme for efficient treatment of MRSA infections.
Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Animales , Antibacterianos/farmacología , Humanos , Peróxido de Hidrógeno/farmacología , Ratones , Molibdeno/farmacología , Terapia FototérmicaRESUMEN
Nanovaccine-based immunotherapy (NBI) has the ability to initiate dendritic cell (DC)-mediated tumor-specific immune responses and maintain long-term antitumor immune memory. To date, the mechanism by which the mechanical properties of nanoparticles alter the functions of DCs in NBI remains largely unclear. Here, a soft mesoporous organosilica-based nanovaccine (SMONV) is prepared and the elasticity-dependent effect of the nanovaccine on the underlying DC-mediated immune responses is studied. It is found that the elasticity results in greater internalization of SMONV by DCs, followed by the induction of substantial cytosolic delivery of antigens via endosomal escape, leading to effective DC maturation and antigen cross-presentation. Impressively, elasticity enables SMONV to enhance lymphatic drainage of antigens in vivo, thus stimulating robust humoral and cellular immunity. The results from therapeutic tumor vaccination further reveal that subcutaneously administered SMONV effectively suppresses tumor growth in tumor-bearing mice by evoking antigen-specific CD8+ T-cell immune responses, mitigating regulatory T-cell-mediated immunosuppression, and increasing central memory and effector memory T-cell populations. Furthermore, combinatorial immunization with SMONV and anti-PD-L1 blocking antibodies results in an amplified therapeutic effect on tumor-bearing mice. These findings reveal the elastic effect of the nanovaccine on DC-mediated immune responses, and the prepared SMONV represents a facile and powerful strategy for antitumor immunotherapy.
Asunto(s)
Vacunas contra el Cáncer , Nanopartículas , Neoplasias , Animales , Antígenos , Linfocitos T CD8-positivos , Células Dendríticas , Inmunoterapia/métodos , Ratones , Ratones Endogámicos C57BL , Neoplasias/terapiaRESUMEN
Although quantum dots (QDs) have shown great potential for various biomedical applications, their potential toxicity still needs to be comprehensively investigated. Previous studies showed that intravenous exposure of CdTe QDs at low concentration did not lead to obvious in vivo toxicity in the long term. However, the influence of CdTe QDs on the gut microbiota and the intestine is still unknown. Here, we explored whether single intravenous injection of CdTe QDs at low concentration can affect the gut microbiota and intestine of mice in short term. The results showed that CdTe QDs caused an imbalance of gut microbiota, especially the rapid increase in Lactobacillus on day 1 post-treatment. Meanwhile, the intestine exhibited the promotion of oxidative stress, inflammatory response, and hemorrhaging on days 5 and 15. These results demonstrate that the gut microbiota and the intestine are very sensitive to the toxicity of low-concentration CdTe QDs. This study provides further insight and method for the biosafety evaluation of nanomaterials.