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1.
Small ; : e2404850, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-39073298

RESUMO

Several natural Chinese herbal medicines have demonstrated considerable potential in facilitating wound healing, while the primary concern remains centered around optimizing formulation and structure to maximize their efficacy. To address this, a natural microneedles drug delivery system is proposed that harnesses gelatinized starch and key Chinese herbal ingredients-aloe vera and berberine. After gelatinized and aged in a well-designed mold, the starch-based microneedles are fabricated with suitable mechanical strength to load components. The resulting Chinese herbal hydrogel microneedles, enriched with integrated berberine and aloe, exhibit antibacterial, anti-inflammatory, and fibroblast growth-promoting properties, thereby facilitating wound healing in the whole process. In vivo experimental results underscore the notable achievements of the microneedles in early-stage antibacterial effects and subsequent tissue reconstruction, contributing significantly to the overall wound healing process. These results emphasize the advantageous combination of traditional Chinese medicine with microneedles, presenting a novel strategy for wound repair and opening new avenues for the application of traditional Chinese medicine.

2.
Small ; 20(36): e2400927, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38726949

RESUMO

Due to the presence of spatial barriers, persistent bacteria, and excessive inflammation in bacteria biofilm-infected wounds, current nanoplatforms cannot effectively address these issues simultaneously during the therapeutic process. Herein, a novel biomimetic photothermal nanoplatform integrating silver and polydopamine nanoparticles (Ag/PDAs) that can damage biofilms, kill bacterial persisters, and reduce inflammation for wound treatment is presented. These findings reveal that Ag/PDAs exhibit a broad-spectrum antimicrobial activity through direct damage to the bacterial membrane structure. Additionally, Ag/PDAs demonstrate a potent photothermal conversion efficiency. When combined with near-infrared (NIR) irradiation, Ag/PDAs effectively disrupt the spatial structure of biofilms and synergistically eradicate the resident bacteria. Furthermore, Ag/PDAs show remarkable anti-inflammatory properties in counteracting bacterium-induced macrophage polarization. The in vivo results confirm that the topical application of Ag/PDAs significantly suppress Staphylococcus aureus biofilm-infected wounds in murine models, concurrently facilitating wound healing. This research provides a promising avenue for the eradication of bacterial biofilms and the treatment of biofilm-infected wounds.


Assuntos
Biofilmes , Indóis , Inflamação , Polímeros , Prata , Staphylococcus aureus , Indóis/química , Indóis/farmacologia , Biofilmes/efeitos dos fármacos , Polímeros/química , Polímeros/farmacologia , Prata/química , Prata/farmacologia , Animais , Staphylococcus aureus/efeitos dos fármacos , Inflamação/tratamento farmacológico , Inflamação/patologia , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Cicatrização/efeitos dos fármacos , Nanopartículas/química
3.
Small ; 19(36): e2302347, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37127862

RESUMO

Reactive oxygen species (ROS)-mediated biological catalysis involves serial programmed enzymatic reactions and plays an important part against infectious diseases; while the spatiotemporal control of catalytic treatment to break the limitations of the disease microenvironment is challenging. Here, a novel spatiotemporal catalytic microneedles patch (CMSP-MNs) integrated with dual-effective Cu2 MoS4 (CMS) and polydopamine (PDA) nanoparticles (NPs) for breaking microenvironment restrictions to treat wound infections is designed. Since CMS NPs are loaded in the needles, CMSP-MNs can catalytically generate diverse ROS to cause effective bacterial inactivation during bacterial infection process. Besides, PDA NPs are encapsulated in the backing layer, which facilitate ROS elimination and oxygen production for solving hypoxic problems in wound microenvironment and alleviating the expression of inflammatory factors during the inflammation process. Based on these features, it is demonstrated through cell and animal experiments that these nanozymes-integrated MNs patches can realize selective regulation of ROS level with bacterial inactivation and inflammatory treatment, resulting in minimized side effects of over-production ROS and effective anti-infected treatment. It is believed that the presented MNs can provide a new therapeutic strategy with spatiotemporal adjustable catalytic properties in biomedical areas.


Assuntos
Infecções Bacterianas , Nanopartículas , Animais , Agulhas , Espécies Reativas de Oxigênio/metabolismo , Bactérias/metabolismo , Catálise
4.
Small ; 18(26): e2201280, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35616035

RESUMO

Tissue bacterial infections are a major pathological factor in many diseases. Effects on this aspect are in focus for the development of coordinated therapeutic strategies for bacterial killing and anti-inflammation. Here, inspired by the biodetoxification capacity of immune cells, multifunctional biomimetic nanovesicles (MϕM-LPs) that are co-assembled by macrophage membranes and artificial lipids to deliver antibiotics for treating bacterial infections, are presented. The macrophage membrane endows the MϕM-LPs with the capacity of lipopolysaccharide and inflammatory cytokine neutralization, while the artificial lipid membrane can be further engineered to increase the fluidity and anchor to bacteria. In addition, the MϕM-LPs can deliver sufficient ciprofloxacin with controllable release to accomplish an excellent antibacterial activity and biodetoxification capacity in vitro. Based on these advantages, it is demonstrated in a mouse model of Staphylococcus aureus (S. aureus) focal infection, that a single injection of the biomimetic nanovesicles can effectively anchor to and eliminate S. aureus in the infected tissue and reduce inflammatory cytokine levels. Thus, the tissue regeneration and collagen deposition can be accelerated. These results indicate the potential values of integrating natural and artificial membrane materials as a multifunctional biomimetic drug delivery system to treat bacterial infections.


Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Animais , Antibacterianos/uso terapêutico , Biomimética , Citocinas , Lipopolissacarídeos/farmacologia , Macrófagos , Membranas Artificiais , Camundongos , Infecções Estafilocócicas/tratamento farmacológico
5.
Small ; 16(40): e2001099, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32893455

RESUMO

Nanozymes with unique enzyme-like catalytic properties and versatile functionalities are particularly attractive for the treatment of bacterial infections, especially for combating drug-resistant bacteria. However, inherently low catalytic activity significantly limits their antibacterial performance. Herein, a new near-infrared II (NIR-II) light responsive nanozyme (Cu2 MoS4 nanoplates, CMS NPs) is developed for efficient eradication of multidrug-resistant (MDR) bacteria. CMS NPs with intrinsic dual enzyme-like property can generate reactive oxygen species (ROS) by catalysis. Importantly, CMS NPs show NIR-II light enhanced oxidase- and peroxidase-like catalytic activities to improve ROS generation for highly efficient killing of bacteria. In vitro results demonstrate that CMS NPs (40 µg mL-1 ) achieve rapid killing of 8 log MDR Escherichia coli and 6 log MDR Staphylococcus aureus (S. aureus) under NIR-II light irradiation (1064 nm, 1 W cm-2 ) in 10 min. Moreover, CMS NPs exhibit excellent therapeutic efficacy of MDR S. aureus infection in vivo as well as negligible toxicity to cells and animals, indicating their potential use as antibacterial agents. This work provides a novel antibacterial strategy by combining the catalytic generation of ROS and NIR-II photothermal effect of nanozymes for efficient treatment of MDR bacteria-related infections.


Assuntos
Farmacorresistência Bacteriana Múltipla , Staphylococcus aureus , Animais , Antibacterianos/farmacologia , Bactérias , Escherichia coli
6.
Small ; 13(5)2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27982538

RESUMO

During recent decades, a giant leap in the development of nanotechnology has been witnessed. Numerous nanomaterials with different dimensions and unprecedented features have been developed and provided unimaginably wide scope to solve the challenging problems in biomedicine, such as cancer diagnosis and therapy. Recently, two-dimensional (2D) transition metal dichalcogenide (TMDC) nanosheets (NSs), including MoS2 , WS2 , and etc., have emerged as novel inorganic graphene analogues and attracted tremendous attention due to their unique structures and distinctive properties, and opened up great opportunities for biomedical applications, including ultrasensitive biosensing, biological imaging, drug delivery, cancer therapy, and antibacterial treatment. A comprehensive overview of different synthetic methods of ultrathin 2D TMDC NSs and their state-of-the-art biomedical applications, especially those that have appeared in the past few years, is presented. At the end of this review, the future opportunities and challenges for 2D TMDC NSs in biomedicine are also discussed.


Assuntos
Técnicas Biossensoriais/métodos , Coloides/química , Nanoestruturas/química , Eletroquímica/métodos , Microscopia de Força Atômica/métodos , Nanotecnologia/métodos
7.
Adv Sci (Weinh) ; 11(23): e2309622, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38582511

RESUMO

Bacterial skin infections are highly prevalent and pose a significant public health threat. Current strategies are primarily focused on the inhibition of bacterial activation while disregarding the excessive inflammation induced by dead bacteria remaining in the body and the effect of the acidic microenvironment during therapy. In this study, a novel dual-functional MgB2 microparticles integrated microneedle (MgB2 MN) patch is presented to kill bacteria and eliminate dead bacteria for skin infection management. The MgB2 microparticles not only can produce a local alkaline microenvironment to promote the proliferation and migration of fibroblasts and keratinocytes, but also achieve >5 log bacterial inactivation. Besides, the MgB2 microparticles effectively mitigate dead bacteria-induced inflammation through interaction with lipopolysaccharide (LPS). With the incorporation of these MgB2 microparticles, the resultant MgB2 MN patches effectively kill bacteria and capture dead bacteria, thereby mitigating these bacteria-induced inflammation. Therefore, the MgB2 MN patches show good therapeutic efficacy in managing animal bacterial skin infections, including abscesses and wounds. These results indicate that reactive metal borides-integrated microneedle patches hold great promise for the treatment of clinical skin infections.


Assuntos
Antibacterianos , Agulhas , Animais , Antibacterianos/administração & dosagem , Camundongos , Dermatopatias Bacterianas/microbiologia , Dermatopatias Bacterianas/tratamento farmacológico , Modelos Animais de Doenças , Humanos , Adesivo Transdérmico , Microinjeções/métodos
8.
Int Immunopharmacol ; 138: 112473, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-38943977

RESUMO

As the resident immune cells in the central nervous system, microglia exhibit a 'sensitized' or 'primed' phenotype with dystrophic morphology and dysregulated functions in aged brains. Although studies have demonstrated the inflammatory profile of aged microglia in several neurological diseases, this issue is largely uncertain in stroke. Consequently, this study investigated the effects of primed and repopulated microglia on post-ischemic brain injury in aged mice. We replaced primed microglia with newly repopulated microglia through pharmacological administration and withdrawal of the colony-stimulating factor 1 receptor (CSF1R) inhibitor, PLX3397. Further, we performed a series of behavioral tests and flow cytometry in mouse models of middle cerebral artery occlusion (MCAO) to study the effects of microglial replacement on ischemic injury in the aged brain. With depletion and subsequent repopulation of microglia in MCAO mice, microglial replacement in aged mice improved neurological function and decreased brain infarction. This protective effect was accompanied by the reduction of peripheral immune cells infiltrating into brains. We showed that the repopulated microglia expressed elevated neuroprotective factors (including Cluster of Differentiation 206, transforming growth factor-ß, and interleukin-10) and diminished expression of inflammatory markers (including Cluster of Differentiation 86, interleukin-6, and tumor necrosis factor α). Moreover, microglial replacement protected the blood-brain barrier and relieved neuronal death in aged mice subjected to 60 min of MCAO. These results imply that the replacement of microglia in the aged brain may alleviate brain damage and neuroinflammation, and therefore, ischemic brain damage. Thus, targeting microglia could be a promising therapeutic strategy for ischemic stroke.


Assuntos
Envelhecimento , Infarto da Artéria Cerebral Média , Camundongos Endogâmicos C57BL , Microglia , Doenças Neuroinflamatórias , Fármacos Neuroprotetores , Animais , Microglia/efeitos dos fármacos , Microglia/imunologia , Masculino , Camundongos , Infarto da Artéria Cerebral Média/imunologia , Infarto da Artéria Cerebral Média/patologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/patologia , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Pirróis/farmacologia , Pirróis/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Encéfalo/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Modelos Animais de Doenças , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/antagonistas & inibidores , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos
9.
J Colloid Interface Sci ; 657: 611-618, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38071810

RESUMO

Nanozymes hold great prospects for bacteria-infected wound management, yet the spatial control of their catalytic activity in infected area and normal tissues remains mired by the heterogeneity of tissue microenvironment. Here, we develop a novel two-dimensional ternary chalcogenide nanodots (Cu2MoS4, CMS NDs) with renal clearable ability and controlled catalytic activity for bacteria-infected wound treatment. The two-dimensional CMS NDs (∼4 nm) are prepared by a simple microwave-assisted chemical synthetic route. Our results show that CMS NDs not only have peroxidase-like activity in a pH-dependent manner (pH < 5.5). Based on the generation of hydroxyl radical (OH) by adding H2O2, CMS NDs show > 2 log bacterial inactivation for both Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli (E. coli) under the acidic condition. Moreover, CMS NDs show good biocompatibility and can be excreted by the kidney in mice. In vivo results display that CMS NDs show good therapeutic effect against bacteria infected wound in the presence of H2O2, but no damage for normal tissues. Taken together, this work provides a renal clearable two-dimensional nanozyme with spatially controlled catalytic activity for the treatment of wounds and bacterial infections on the skin surface.


Assuntos
Infecções Bacterianas , Staphylococcus aureus Resistente à Meticilina , Camundongos , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Escherichia coli , Peróxido de Hidrogênio/química
10.
Nanoscale ; 16(24): 11669-11678, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38855849

RESUMO

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.


Assuntos
Biofilmes , Fluorocarbonos , Gálio , Staphylococcus aureus Resistente à Meticilina , Oxigênio , Protoporfirinas , Infecções Estafilocócicas , Terapia por Ultrassom , Animais , Fluorocarbonos/química , Fluorocarbonos/farmacologia , Camundongos , Gálio/química , Gálio/farmacologia , Protoporfirinas/química , Protoporfirinas/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Oxigênio/química , Infecções Estafilocócicas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos Endogâmicos BALB C , Feminino , Pentanos
11.
Smart Med ; 2(3): e20220025, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39188347

RESUMO

Wound infections continuously impose a huge economic and social burden on public healthcare. Despite the effective treatment of bacteria-infected wounds after using traditional antibiotics, the misuse of antibiotics usually causes the spread of bacterial resistance and decreases therapeutic outcomes. Therefore, the development of efficient antibacterial agents is urgently needed. Nanozymes, as a new generation of artificial enzymes, combine the intrinsic abilities of nanomaterials and natural enzymes. Recently, nanozymes has been widely developed to kill bacteria and treat wound infections by catalyzing the generation of various reactive oxygen species. Thus, this new concept of "antibacterial nanozymes" will promote the further advances of connecting nanozymes and bacterial elimination. To highlight these achievements, we summarize different types of antibacterial nanozymes for wound healing. It is believed that such a promising therapeutic strategy of developing antibacterial nanozymes will make a great contribution in the field of skin regeneration. We expect that antibacterial nanozymes will play the significant roles in both basic research and clinical applications.

12.
Macromol Biosci ; 23(5): e2300006, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36951403

RESUMO

How to avoid the microenvironment limitations in the therapeutic process of pressure ulcers is still challenging. The development of a functional gel can kill bacteria and scavenge reactive oxygen species (ROS), which is urgently required in the therapeutic process of pressure ulcers. Herein, an in situ sprayed gel is developed with silver nanoparticles (AgNPs) and polydopamine (PDA) NPs (APG) to obviate microenvironment restrictions in treating pressure ulcers. The gel is constructed by spraying sodium alginate solution and CaCl2 solution. AgNPs serve as an antibacterial agent in the formed gel, which can effectively cause bacterial inactivation and show more than 5 log (>99.999%) bacterial killing efficiency against methicillin-resistant S. aureus (MRSA), Staphylococcus aureus (S. aureus), and Escherichia coli (E. coli) in vitro. Meanwhile, PDA NPs serve as the antioxidative agent in the formed gel, which can facilitate the elimination of ROS to address the high ROS problem in wound microenvironment. Based on these features, it is demonstrated through cell and animal experiments that the AgNPs and PDA NPs incorporated gel can realize the effective treatment of MRSA-infected and hydrogen peroxide (H2 O2 )-sensitized pressure ulcers. It is believed that the designed system by a simple spray-coating approach can provide a new therapeutic strategy in biomedical areas.


Assuntos
Nanopartículas Metálicas , Staphylococcus aureus Resistente à Meticilina , Úlcera por Pressão , Animais , Staphylococcus aureus , Úlcera por Pressão/tratamento farmacológico , Espécies Reativas de Oxigênio , Escherichia coli , Nanopartículas Metálicas/uso terapêutico , Prata/farmacologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Testes de Sensibilidade Microbiana
13.
Adv Sci (Weinh) ; 10(21): e2300456, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37193644

RESUMO

The tumor-suppressing efficacy of either chemotherapeutics or gaseous drugs has been confirmed in treating the triple negative breast cancer (TNBC), while the efficacy of single treatment is usually dissatisfactory. Herein, a novel ultrasound responsive natural pollen delivery system is presented to simultaneously load chemotherapeutics and gaseous drugs for synergistic treatment of TNBC. The hollow structure of pollen grains carries oxygen-enriched perfluorocarbon (PFC), and the porous spinous process structure adsorbs the chemotherapeutic drug doxorubicin (DOX) (PO/D-PGs). Ultrasound can trigger the oxygen release from PFC and excite DOX, which is not only a chemotherapeutic but also a sonosensitizer, to realize chemo-sonodynamic therapy. The PO/D-PGs are demonstrated to effectively enhance oxygen concentration and increase the production of reactive oxygen species in the presence of low-intensity ultrasound, synergistically enhancing the tumor killing ability. Thus, the synergistic therapy based on ultrasound-facilitated PO/D-PGs significantly enhances the antitumor effect in the mouse TNBC model. It is believed that the proposed natural pollen cross-state microcarrier can be used as an effective strategy to enhance chemo-sonodynamic therapy for TNBC.


Assuntos
Nanopartículas , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Nanopartículas/química , Doxorrubicina/química , Terapia Combinada , Oxigênio
14.
Acta Biomater ; 157: 200-209, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36494009

RESUMO

Medical patches hold great prospects for diabetic wound administration, while their practical effects in diabetic wound management remain mired by the complexity of wound microenvironments. Here, inspired by the biological processes of glucose metabolism, we present a catalytic microneedle patch that encapsulates near-infrared-II responsive and dual-nanozyme active Au-Cu2MoS4 nanosheets (Au-CMS NSs) for treating diabetic wound infection. Since microneedle patches have great tissue penetration ability, the Au-CMS NSs can be delivered to deep tissues and fully interact with wound environments. Benefitting from the dual nanozyme activities (glucose oxidase and catalase) and near-infrared-II photothermal performances of Au-CMS NSs, the composited catalytic patch realizes in situ glucose consumption, oxygen generation, and bacterial elimination. Notably, their repeatability of near-infrared-II responsive antibacterial capability has been proved both in vitro and in diabetic mice against methicillin-resistant Staphylococcus aureus. The catalytic patch can find wide catalytic applications in wound care and infection prevention. STATEMENT OF SIGNIFICANCE: Effective treatment of diabetic wound infection remains still challenging in the clinic owing to the complex wound microenvironments. Herein, inspired by the biological processes of glucose metabolism in lives, we propose a novel strategy to treat wound infections by modulating the diabetic wound microenvironments. A near-infrared-II (NIR-II) responsive biocatalytic microneedle patch with both glucose oxidase- and catalase-like activities capable of killing bacteria, reducing glucose level, and supplying O2 is developed. The patch not only achieves efficient antibacterial outcomes in vitro, but also is a valuable wound patch for efficient treatment of MRSA-infected wounds in diabetic mice. We anticipate that this therapeutic strategy will provide the applications in chronic inflammation and infections.


Assuntos
Diabetes Mellitus Experimental , Staphylococcus aureus Resistente à Meticilina , Infecção dos Ferimentos , Animais , Camundongos , Catalase , Diabetes Mellitus Experimental/terapia , Glucose Oxidase , Fototerapia , Infecção dos Ferimentos/terapia , Oxigênio , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Glucose
15.
Adv Healthc Mater ; 12(17): e2203028, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36807733

RESUMO

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.


Assuntos
Vacinas Anticâncer , Nanopartículas , Neoplasias , Humanos , Neoplasias/terapia , Apresentação de Antígeno , Antígenos/farmacologia , Imunoterapia , Células Dendríticas , Vacinas Anticâncer/farmacologia
16.
Int J Nanomedicine ; 17: 2735-2750, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35769516

RESUMO

Background: Bacterial biofilm-related wound infections threaten human health due to the lack of efficient treatments. Therefore, developing a novel strategy for wound infection care is urgently needed. Methods: Cube-shaped Cu2WS4 nanocrystals (CWSNs) were successfully prepared via a microwave-assisted method. CWSNs, as photocatalysts, were first studied by using fluorescence spectroscopy for their ability to generate reactive oxygen species (ROS). The antibacterial and biofilm inhibition abilities of CWSNs were determined in vitro by using Staphylococcus aureus (S. aureus) as the model bacterium. Moreover, a CWSN gel was prepared and applied to treat S. aureus-infected wounds in mice. The toxicity of the CWSNs was evaluated through in vitro cell and in vivo animal experiments. Results: Studies on the properties of the CWSNs demonstrated that these nanomaterials can catalyze the generation of hydroxyl radicals (•OH) without the addition of H2O2 after visible-light irradiation, indicating their photocatalytic ability. Moreover, the in vitro experimental results showed that the CWSNs not only adhered to the surfaces of S. aureus to kill the bacteria, but also inhibited S. aureus biofilm formation. The in vivo study showed that the CWSN gel produced excellent antibacterial effects against S. aureus infected wounds in mice and effectively promoted wound healing. Furthermore, toxicity tests showed that the CWSNs have negligible toxicity in vitro and in vivo. Conclusion: This work provides a potential photocatalytic antibacterial nanoagent for efficient bacterial killing, inhibition of biofilms growth and wound infection treatment.


Assuntos
Nanopartículas , Infecções Estafilocócicas , Infecção dos Ferimentos , Animais , Antibacterianos/farmacologia , Biofilmes , Peróxido de Hidrogênio/farmacologia , Camundongos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus , Infecção dos Ferimentos/microbiologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-31552242

RESUMO

Bacterial biofilm-related diseases cause serious hazard to public health and bring great challenge to the traditional antibiotic treatment. Photothermal therapy (PTT) has been recognized as a promising alternative solution. However, the therapeutic efficacy of PTT is often compromised by the collateral damage to normal tissues due to the lack of bacteria-targeting capability. Here, a Staphylococcus aureus (S. aureus)-targeted PTT nanoagent is prepared based on antibody (anti-protein A IgG), polydopamine (PDA), and PEG-SH (thiolated poly (ethylene glycol)) functionalized MoS2 nanosheets (MoS2@PDA-PEG/IgG NSs, MPPI NSs). The PDA was used as bio-nano interface to facilitate the covalent conjugation of antibody and PEG-SH onto the surface of MoS2 NSs via facile catechol chemistry. Targeted PTT of MPPI NSs shows excellent inactivation efficiency of larger than 4 log (>99.99%) to S. aureus both in biofilms (in vitro) and in infected tissues (in vivo) without causing damage to normal mammalian cells. By contrast, non-targeted PTT of MoS2@PDA-PEG NSs (MPP NSs) only kills S. aureus by <90% in vitro and <50% in vivo. As a result, S. aureus focal infection in mice healed much faster after PTT of MPPI NSs than that of MPP NSs. The superiority of targeted PTT may originate from the efficient accumulation and close binding of PTT agents to bacterial cells. Therefore, MPPI NSs with bacteria-targeting capability are promising photothermal agents for effective treatment of S. aureus focal infection.

18.
ACS Nano ; 13(12): 13797-13808, 2019 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-31696705

RESUMO

Antibacterial agents with high antibacterial efficiency and bacteria-binding capability are highly desirable. Herein, we describe the successful preparation of Cu2WS4 nanocrystals (CWS NCs) with excellent antibacterial activity. CWS NCs with small size (∼20 nm) achieve more than 5 log (>99.999%) inactivation efficiency of both Staphylococcus aureus (Gram-positive) and Escherichia coli (Gram-negative) at low concentration (<2 µg mL-1) with or without ambient light, which is much better than most of the reported antibacterial nanomaterials (including Ag, TiO2, etc.) and even better than the widely used antibiotics (vancomycin and daptomycin). Antibacterial mechanism study showed that CWS NCs have both enzyme-like (oxidase and peroxidase) properties and selective bacteria-binding ability, which greatly facilitate the production of reactive oxygen species to kill bacteria. Animal experiments further indicated that CWS NCs can effectively treat wounds infected with methicillin-resistant Staphylococcus aureus (MRSA). This work demonstrates that CWS NCs have the potential as effective antibacterial nanozymes for the treatment of bacterial infection.


Assuntos
Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Viabilidade Microbiana , Nanopartículas/química , Sulfetos/toxicidade , Animais , Escherichia coli/ultraestrutura , Feminino , Células HeLa , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Nanopartículas/toxicidade , Nanopartículas/ultraestrutura , Ratos Sprague-Dawley
19.
ACS Appl Mater Interfaces ; 10(40): 34455-34463, 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-30211531

RESUMO

Cationic quaternary ammonium (QA) groups and reactive oxygen species as two main approaches for antibacterial study have been intensively studied. Herein, we report a multifunctional antimicrobial agent (porphyrin-POSS-OPVE, PPO), which combines bacterial membrane intercalation, high density of local QA groups, efficient energy transfer, significantly reduced aggregation, and high water solubility into one single molecule. The light-harvesting PPO contains multiple donor-absorbing arms (oligo( p-phenylenevinylene) electrolytes, OPVEs) on its globular periphery and a central porphyrin acceptor in the core by using three-dimensional nanocages (polyhedral oligomeric silsesquioxanes, POSSs) as bridges. The antiaggregation ability of POSS and the highly efficient energy transfer from multiple OPVE arms to porphyrin could greatly amplify singlet oxygen generation in PPO. Particularly, OPVEs with QA terminal chains were able to intercalate into Escherichia coli membranes, which facilitated 1O2 diffusion and bacterial cell membrane disintegration by QA groups. The increased local cationic QA charges in OPVE arms can also enhance the biocidal activity of PPO. Benefiting from these satisfactory features, PPO exhibits multiamplified antibacterial efficacy under a very low concentration level and white light dose (400-700 nm, 6 mW·cm-2, 5 min, 1.8 J·cm-2) to Escherichia coli (8 µM) and Staphylococcus aureus (500 nM). Therefore, PPO shows great potential for photodynamic antimicrobial chemotherapy at a much lower irradiation light dose and photosensitizer concentration level compared to previous reports.


Assuntos
Antibacterianos , Escherichia coli/metabolismo , Compostos de Organossilício , Porfirinas , Compostos de Amônio Quaternário , Espécies Reativas de Oxigênio/metabolismo , Antibacterianos/química , Antibacterianos/farmacologia , Membrana Celular/metabolismo , Compostos de Organossilício/química , Compostos de Organossilício/farmacologia , Porfirinas/química , Porfirinas/farmacologia , Compostos de Amônio Quaternário/química , Compostos de Amônio Quaternário/farmacologia
20.
Nanoscale ; 8(5): 2720-6, 2016 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-26758473

RESUMO

Photothermal therapy (PTT) is a promising cancer treatment with both high effectiveness and fewer side effects. However, an ideal PTT agent not only needs strong absorption of near-infrared (NIR) light and high photothermal conversion efficiency, but also needs good biocompatibility, stability, and small size, which makes the design and preparation of a novel PTT agent a great challenge. In this work, we developed an ultrasonication-assisted liquid exfoliation method for the direct preparation of ultrasmall (2-3 nm) MoSe2 nanodots (NDs) in aqueous solution and demonstrated their superior properties as a PTT agent. The as-prepared MoSe2 NDs have strong absorption of NIR light and high photothermal conversion efficiency of about 46.5%. In vitro cellular experiments demonstrate that MoSe2 NDs have negligible cytotoxicity and can efficiently kill HeLa cells (human cervical cell line) under NIR laser (785 nm) irradiation.


Assuntos
Molibdênio/química , Nanopartículas/química , Selênio/química , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Células HeLa , Humanos , Raios Infravermelhos , Microscopia Eletrônica de Transmissão , Molibdênio/farmacologia , Nanopartículas/uso terapêutico , Neoplasias/terapia , Espectroscopia Fotoeletrônica , Fototerapia , Polímeros/química , Selênio/farmacologia , Água/química , Difração de Raios X
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