RESUMEN

Insulin resistance and pancreatic ß-cell dysfunction are the main pathogenesis of type 2 diabetes mellitus (T2DM). However, insulin therapy and diabetes medications do not effectively solve the two problems simultaneously. In this study, a biomimetic oral hydrogen nanogenerator that leverages the benefits of edible plant-derived exosomes and hydrogen therapy was constructed to overcome this dilemma by modulating gut microbiota and ameliorating oxidative stress and inflammatory responses. Hollow mesoporous silica (HMS) nanoparticles encapsulating ammonia borane (A) were used to overcome the inefficiency of H2 delivery in traditional hydrogen therapy, and exosomes originating from ginger (GE) were employed to enhance biocompatibility and regulate intestinal flora. Our study showed that HMS/A@GE not only considerably ameliorated insulin resistance and liver steatosis, but inhibited the dedifferentiation of islet ß-cell and enhanced pancreatic ß-cell proportion in T2DM model mice. In addition to its antioxidant and anti-inflammatory effects, HMS/A@GE augmented the abundance of Lactobacilli spp. and tryptophan metabolites, such as indole and indole acetic acid, which further activated the AhR/IL-22 pathway to improve intestinal-barrier function and metabolic impairments. This study offers a potentially viable strategy for addressing the current limitations of diabetes treatment by integrating gut-microbiota remodelling with antioxidant therapies.

Asunto(s)

Antioxidantes , Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Resistencia a la Insulina , Células Secretoras de Insulina , Nanopartículas , Células Secretoras de Insulina/efectos de los fármacos , Células Secretoras de Insulina/metabolismo , Animales , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Antioxidantes/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Nanopartículas/química , Ratones , Masculino , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Ratones Endogámicos C57BL , Zingiber officinale/química , Dióxido de Silicio/química , Exosomas/metabolismo , Biomimética/métodos , Estrés Oxidativo/efectos de los fármacos

RESUMEN

Minimally invasive transcatheter interventional therapy utilizing cardiac occluders represents the primary approach for addressing congenital heart defects and left atrial appendage (LAA) thrombosis. However, incomplete endothelialization and delayed tissue healing after occluder implantation collectively compromise clinical efficacy. In this study, we have customized a recombinant humanized collagen type I (rhCol I) and developed an rhCol I-based extracellular matrix (ECM)-mimetic coating. The innovative coating integrates metal-phenolic networks with anticoagulation and anti-inflammatory functions as a weak cross-linker, combining them with specifically engineered rhCol I that exhibits high cell adhesion activity and elicits a low inflammatory response. The amalgamation, driven by multiple forces, effectively serves to functionalize implantable materials, thereby responding positively to the microenvironment following occluder implantation. Experimental findings substantiate the coating's ability to sustain a prolonged anticoagulant effect, enhance the functionality of endothelial cells and cardiomyocyte, and modulate inflammatory responses by polarizing inflammatory cells into an anti-inflammatory phenotype. Notably, occluder implantation in a canine model confirms that the coating expedites reendothelialization process and promotes tissue healing. Collectively, this tailored ECM-mimetic coating presents a promising surface modification strategy for improving the clinical efficacy of cardiac occluders.

Asunto(s)

Materiales Biocompatibles Revestidos , Matriz Extracelular , Cicatrización de Heridas , Animales , Matriz Extracelular/metabolismo , Perros , Humanos , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Cicatrización de Heridas/efectos de los fármacos , Colágeno Tipo I/metabolismo , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Células Endoteliales de la Vena Umbilical Humana , Repitelización/efectos de los fármacos , Adhesión Celular/efectos de los fármacos

RESUMEN

Chemotherapy-induced cellular senescence leads to an increased proportion of cancer stem cells (CSCs) in breast cancer (BC), contributing to recurrence and metastasis, while effective means to clear them are currently lacking. Herein, we aim to develop new approaches for selectively killing senescent-escape CSCs. High CD276 (95.60%) expression in multidrug-resistant BC cells, facilitates immune evasion by low-immunogenic senescent escape CSCs. CALD1, upregulated in ADR-resistant BC, promoting senescent-escape of CSCs with an anti-apoptosis state and upregulating CD276, PD-L1 to promote chemoresistance and immune escape. We have developed a controlled-released thermosensitive hydrogel containing pH- responsive anti-CD276 scFV engineered biomimetic nanovesicles to overcome BC in primary, recurrent, metastatic and abscopal humanized mice models. Nanovesicles coated anti-CD276 scFV selectively fuses with cell membrane of senescent-escape CSCs, then sequentially delivers siCALD1 and ADR due to pH-responsive MnP shell. siCALD1 together with ADR effectively induce apoptosis of CSCs, decrease expression of CD276 and PD-L1, and upregulate MHC I combined with Mn2+ to overcome chemoresistance and promote CD8+T cells infiltration. This combined therapeutic approach reveals insights into immune surveillance evasion by senescent-escape CSCs, offering a promising strategy to immunotherapy effectiveness in cancer therapy.

Asunto(s)

Neoplasias de la Mama , Senescencia Celular , Resistencia a Antineoplásicos , Células Madre Neoplásicas , Humanos , Animales , Neoplasias de la Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Resistencia a Antineoplásicos/efectos de los fármacos , Femenino , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Senescencia Celular/efectos de los fármacos , Línea Celular Tumoral , Ratones , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Ingeniería Genética/métodos , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Nanopartículas/química , Anticuerpos de Cadena Única/química , Escape del Tumor/efectos de los fármacos , Antígeno B7-H1/metabolismo , Apoptosis/efectos de los fármacos , Biomimética/métodos , Antígenos B7

RESUMEN

Acute Myocardial Infarction (AMI) has seen rising cases, particularly in younger people, leading to public health concerns. Standard treatments, like coronary artery recanalization, often don't fully repair the heart's microvasculature, risking heart failure. Advances show that Mesenchymal Stromal Cells (MSCs) transplantation improves cardiac function after AMI, but the harsh microenvironment post-AMI impacts cell survival and therapeutic results. MSCs aid heart repair via their membrane proteins and paracrine extracellular vesicles that carry microRNA-125b, which regulates multiple targets, preventing cardiomyocyte death, limiting fibroblast growth, and combating myocardial remodeling after AMI. This study introduces ultrasound-responsive phase-change bionic nanoparticles, leveraging MSCs' natural properties. These particles contain MSC membrane and microRNA-125b, with added macrophage membrane for stability. Using Ultrasound Targeted Microbubble Destruction (UTMD), this method targets the delivery of MSC membrane proteins and microRNA-125b to AMI's inflamed areas. This aims to enhance cardiac function recovery and provide precise, targeted AMI therapy.

Asunto(s)

Células Madre Mesenquimatosas , MicroARNs , Infarto del Miocardio , Nanopartículas , Infarto del Miocardio/terapia , Animales , Nanopartículas/química , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , MicroARNs/metabolismo , MicroARNs/genética , Masculino , Recuperación de la Función , Trasplante de Células Madre Mesenquimatosas/métodos , Humanos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Ratones , Microburbujas , Ondas Ultrasónicas

RESUMEN

Introduction: Immunotherapy has led to a paradigm shift in reinvigorating treatment of cancer. Nevertheless, tumor associated macrophages (TAMs) experience functional polarization on account of the generation of suppressive metabolites, contributing to impaired antitumor immune responses. Methods: Hence, metabolic reprogramming of tumor microenvironment (TME) can synergistically improve the efficacy of anti-tumor immunotherapy. Herein, we engineered an iron-based nanoplatform termed ERFe3O4 NPs. This platform features hollow Fe3O4 nanoparticles loaded with the natural product emodin, the outer layer is coated with red blood cell membrane (mRBCs) inserted with DSPE-PEG2000-galactose. This effectively modulates lactate production, thereby reversing the tumor immune suppressive microenvironment (TIME). Results: The ERFe3O4 NPs actively targeted TAMs on account of their ability to bind to M2-like TAMs with high expression of galectin (Mgl). ERFe3O4 NPs achieved efficient ability to reverse TIME via the production of reducing lactate and prompting enrichment iron of high concentrations. Furthermore, ERFe3O4 NPs resulted in heightened expression of CD16/32 and enhanced TNF-α release, indicating promotion of M1 TAMs polarization. In vitro and in vivo experiments revealed that ERFe3O4 NPs induced significant apoptosis of tumor cells and antitumor immune response. Discussion: This study combines Traditional Chinese Medicine (TCM) with nanomaterials to synergistically reprogram TAMs and reverse TIME, opening up new ideas for improving anti-tumor immunotherapy.

Asunto(s)

Inmunoterapia , Microambiente Tumoral , Microambiente Tumoral/efectos de los fármacos , Animales , Inmunoterapia/métodos , Ratones , Línea Celular Tumoral , Humanos , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/inmunología , Ratones Endogámicos C57BL , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Apoptosis/efectos de los fármacos , Hierro/química , Femenino

RESUMEN

The alarming rise in global antimicrobial resistance underscores the urgent need for effective antibacterial drugs. Drawing inspiration from the bacterial-entrapment mechanism of human defensin 6, we have fabricated biomimetic peptide nanonets composed of multiple functional fragments for bacterial eradication. These biomimetic peptide nanonets are designed to address antimicrobial resistance challenges through a dual-approach strategy. First, the resulting nanofibrous networks trap bacteria and subsequently kill them by loosening the membrane structure, dissipating proton motive force, and causing multiple metabolic perturbations. Second, these trapped bacterial clusters reactivate macrophages to scavenge bacteria through enhanced chemotaxis and phagocytosis via the PI3K-AKT signaling pathway and ECM-receptor interaction. In vivo results have proven that treatment with biomimetic peptide nanonets can alleviate systemic bacterial infections without causing noticeable systemic toxicity. As anticipated, the proposed strategy can address stubborn infections by entrapping bacteria and awakening antibacterial immune responses. This approach might serve as a guide for the design of bioinspired materials for future clinical applications.

Asunto(s)

Antibacterianos , Materiales Biomiméticos , Macrófagos , Macrófagos/efectos de los fármacos , Macrófagos/microbiología , Macrófagos/metabolismo , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Humanos , Animales , Ratones , Péptidos/química , Péptidos/farmacología , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Células RAW 264.7 , Fagocitosis/efectos de los fármacos , Escherichia coli/efectos de los fármacos

RESUMEN

BACKGROUND: Ulcerative colitis (UC) is defined by persistent inflammatory processes within the gastrointestinal tract of uncertain etiology. Current therapeutic approaches are limited in their ability to address oxidative stress, inflammation, barrier function restoration, and modulation of gut microbiota in a coordinated manner to maintain intestinal homeostasis. RESULTS: This study involves the construction of a metal-phenolic nanozyme (Cur-Fe) through a ferric ion-mediated oxidative coupling of curcumin. Cur-Fe nanozyme exhibits superoxide dismutase (SOD)-like and •OH scavenging activities, demonstrating significant anti-inflammatory and anti-oxidant properties for maintaining intracellular redox balance in vitro. Drawing inspiration from Escherichia coli Nissle 1917 (EcN), a biomimetic Cur-Fe nanozyme (CF@EM) is subsequently developed by integrating Cur-Fe into the EcN membrane (EM) to improve the in vivo targeting ability and therapeutic effectiveness of the Cur-Fe nanozyme. When orally administered, CF@EM demonstrates a strong ability to colonize the inflamed colon and restore intestinal redox balance and barrier function in DSS-induced colitis models. Importantly, CF@EM influences the gut microbiome towards a beneficial state by enhancing bacterial diversity and shifting the compositional structure toward an anti-inflammatory phenotype. Furthermore, analysis of intestinal microbial metabolites supports the notion that the therapeutic efficacy of CF@EM is closely associated with bile acid metabolism. CONCLUSION: Inspired by gut microbes, we have successfully synthesized a biomimetic Cur-Fe nanozyme with the ability to inhibit inflammation and restore intestinal homeostasis. Collectively, without appreciable systemic toxicity, this work provides an unprecedented opportunity for targeted oral nanomedicine in the treatment of ulcerative colitis.

Asunto(s)

Colitis Ulcerosa , Microbioma Gastrointestinal , Homeostasis , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Animales , Homeostasis/efectos de los fármacos , Ratones , Microbioma Gastrointestinal/efectos de los fármacos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/química , Curcumina/farmacología , Curcumina/química , Ratones Endogámicos C57BL , Escherichia coli/efectos de los fármacos , Administración Oral , Biomimética/métodos , Masculino , Estrés Oxidativo/efectos de los fármacos , Modelos Animales de Enfermedad , Antioxidantes/farmacología , Antioxidantes/química

RESUMEN

Fibrosarcoma, a malignant mesenchymal tumor, is characterized by aggressive invasiveness and a high recurrence rate, leading to poor prognosis. Anthracycline drugs, such as doxorubicin (DOX), represent the frontline chemotherapy for fibrosarcoma, but often exhibit suboptimal efficacy. Recently, exploiting the stimulator of interferon genes (STING)-mediated innate immunity has emerged as a hopeful strategy for cancer treatment. Integrating chemotherapy with immunomodulators in chemo-immunotherapy has shown potential for enhancing treatment outcomes. Herein, we introduce an advanced dendritic cell (DC) nanovaccine, cGAMP@PLGA@CRTM (GP@CRTM), combined with low-dose DOX to enhance fibrosarcoma chemo-immunotherapy. The nanovaccine consists of poly(lactic-co-glycolic acid) (PLGA) nanoparticles encapsulating the STING agonist 2,3-cGAMP (cGAMP@PLGA, GP) as its core, and a calreticulin (CRT) high-expressing fibrosarcoma cell membrane (CRTM) as the shell. Exposing CRT on the vaccine surface aids in recruiting DCs and stimulating uptake, facilitating efficient simultaneous delivery of STING agonists and tumor antigens to DCs. This dual delivery method effectively activates the STING pathway in DCs, triggering sustained immune stimulation. Simultaneously, low-dose DOX reduces chemotherapy-related side effects, directly kills a subset of tumor cells, and increases tumor immunogenicity, thus further amplifying immune therapeutic performance. Hence, these findings demonstrate the potential of DC nanovaccine GP@CRTM as a booster for chemotherapy. Synergistically combining low-dose DOX with the DC nanovaccine emerges as a powerful chemo-immunotherapy strategy, optimizing systemic fibrosarcoma therapy.

Asunto(s)

Vacunas contra el Cáncer , Células Dendríticas , Doxorrubicina , Fibrosarcoma , Nanopartículas , Nucleótidos Cíclicos , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos , Células Dendríticas/metabolismo , Fibrosarcoma/tratamiento farmacológico , Fibrosarcoma/patología , Fibrosarcoma/inmunología , Fibrosarcoma/terapia , Animales , Doxorrubicina/farmacología , Doxorrubicina/química , Ratones , Nucleótidos Cíclicos/química , Nucleótidos Cíclicos/farmacología , Nanopartículas/química , Vacunas contra el Cáncer/inmunología , Humanos , Proteínas de la Membrana/metabolismo , Línea Celular Tumoral , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Ratones Endogámicos C57BL , Inmunoterapia , Calreticulina/metabolismo , Nanovacunas

RESUMEN

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that carries the worst prognosis and lacks specific therapeutic targets. To achieve accurate "cargos" delivery at the TNBC site, we herein constructed a novel biomimetic nano-Trojan horse integrating chemotherapy with gene therapy for boosting TNBC treatment. Briefly, we initially introduce the diselenide-bond-containing organosilica moieties into the framework of mesoporous silica nanoparticles (MONs), thereby conferring biodegradability to intratumoral redox conditions in the obtained MONSe. Subsequently, doxorubicin (Dox) and therapeutic miR-34a are loaded into MONSe, thus achieving the combination of chemotherapy and gene-therapy. After homologous tumor cell membrane coating, the ultimate homologous tumor cell-derived biomimetic nano-Trojan horse (namely, MONSe@Dox@miR-34a@CM) can selectively enter the tumor cells in a stealth-like fashion. Notably, such a nanoplatform not only synergistically eradicated the tumor but also inhibited the proliferation of breast cancer stem-like cells (BCSCs) in vitro and in vivo. With the integration of homologous tumor cell membrane-facilitated intratumoral accumulation, excellent biodegradability, and synergistic gene-chemotherapy, our biomimetic nanocarriers hold tremendous promise for the cure of TNBC in the future.

Asunto(s)

Materiales Biomiméticos , Doxorrubicina , MicroARNs , Nanopartículas , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/terapia , Doxorrubicina/química , Doxorrubicina/farmacología , Humanos , Femenino , Animales , Nanopartículas/química , MicroARNs/metabolismo , MicroARNs/genética , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Ratones , Terapia Genética , Línea Celular Tumoral , Dióxido de Silicio/química , Proliferación Celular/efectos de los fármacos , Portadores de Fármacos/química

Asunto(s)

Materiales Biomiméticos , Fibrosis , Animales , Materiales Biomiméticos/farmacología , Microambiente Celular , Ratones , Humanos

RESUMEN

Rationale: Autism spectrum disorder (ASD) represents a complex neurodevelopmental condition lacking specific pharmacological interventions. Given the multifaced etiology of ASD, there exist no effective treatment for ASD. Rapamycin (RAPA) can activate autophagy by inhibiting the mTOR pathway and has exhibited promising effects in treating central nervous system disorders; however, its limited ability to cross the blood-brain barrier (BBB) has hindered its clinical efficacy, leading to substantial side effects. Methods: To address this challenge, we designed a drug delivery system utilizing red blood cell membrane (CM) vesicles modified with SS31 peptides to enhance the brain penetration of RAPA for the treatment of autism. Results: The fabricated SCM@RAPA nanoparticles, with an average diameter of 110 nm, exhibit rapid release of RAPA in a pathological environment characterized by oxidative stress. In vitro results demonstrate that SCM@RAPA effectively activate cellular autophagy, reduce intracellular ROS levels, improve mitochondrial function, thereby ameliorating neuronal damage. SS31 peptide modification significantly enhances the BBB penetration and rapid brain accumulation of SCM@RAPA. Notably, SCM@RAPA nanoparticles demonstrate the potential to ameliorate social deficits, improve cognitive function, and reverse neuronal impairments in valproic acid (VPA)-induced ASD models. Conclusions: The therapeutic potential of SCM@RAPA in managing ASD signifies a paradigm shift in autism drug treatment, holding promise for clinical interventions in diverse neurological conditions.

Asunto(s)

Trastorno del Espectro Autista , Autofagia , Barrera Hematoencefálica , Nanopartículas , Estrés Oxidativo , Sirolimus , Sirolimus/administración & dosificación , Sirolimus/farmacología , Estrés Oxidativo/efectos de los fármacos , Trastorno del Espectro Autista/tratamiento farmacológico , Trastorno del Espectro Autista/metabolismo , Animales , Autofagia/efectos de los fármacos , Nanopartículas/química , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Ratones , Humanos , Sistemas de Liberación de Medicamentos/métodos , Modelos Animales de Enfermedad , Masculino , Materiales Biomiméticos/administración & dosificación , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Biomimética/métodos , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Péptidos/administración & dosificación , Especies Reactivas de Oxígeno/metabolismo , Ácido Valproico/administración & dosificación , Ácido Valproico/farmacología

RESUMEN

Ischemic stroke is a serious neurological disease involving multiple complex physiological processes, including vascular obstruction, brain tissue ischemia, impaired energy metabolism, cell death, impaired ion pump function, and inflammatory response. In recent years, there has been significant interest in cell membrane-functionalized biomimetic nanoparticles as a novel therapeutic approach. This review comprehensively explores the mechanisms and importance of using these nanoparticles to treat acute ischemic stroke with a special emphasis on their potential for actively targeting therapies through cell membranes. We provide an overview of the pathophysiology of ischemic stroke and present advances in the study of biomimetic nanoparticles, emphasizing their potential for drug delivery and precision-targeted therapy. This paper focuses on bio-nanoparticles encapsulated in bionic cell membranes to target ischemic stroke treatment. It highlights the mechanism of action and research progress regarding different types of cell membrane-functionalized bi-onic nanoparticles such as erythrocytes, neutrophils, platelets, exosomes, macrophages, and neural stem cells in treating ischemic stroke while emphasizing their potential to improve brain tissue's ischemic state and attenuate neurological damage and dysfunction. Through an in-depth exploration of the potential benefits provided by cell membrane-functionalized biomimetic nanoparticles to improve brain tissue's ischemic state while reducing neurological injury and dysfunction, this study also provides comprehensive research on neural stem cells' potential along with that of cell membrane-functionalized biomimetic nanoparticles to ameliorate neurological injury and dysfunction. However, it is undeniable that there are still some challenges and limitations in terms of biocompatibility, safety, and practical applications for clinical translation.

Asunto(s)

Materiales Biomiméticos , Membrana Celular , Accidente Cerebrovascular Isquémico , Nanopartículas , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/patología , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Nanopartículas/química , Animales , Membrana Celular/metabolismo , Biomimética/métodos , Sistemas de Liberación de Medicamentos , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo

RESUMEN

The pro-inflammatory/anti-inflammatory polarized phenotypes of macrophages (M1/M2) can be used to predict the success of implant integration. Hence, activating and inducing the transformation of immunocytes that promote tissue repair appears to be a highly promising strategy for facilitating osteo-anagenesis. In a previous study, titanium implants were coated with a graphene oxide-hydroxyapatite (GO-HA) nanocomposite via electrophoretic deposition, and the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) was found to be significantly enhanced when the GO content was 2wt%. However, the effectiveness of the GO-HA nanocomposite coating in modifying the in vivo immune microenvironment still remains unclear. In this study, the effects of GO-HA coatings on osteogenesis were investigated based on the GO-HA-mediated immune regulation of macrophages. The HA-2wt%GO nanocomposite coatings exhibited good biocompatibility and favored M2 macrophage polarization. Meanwhile, they could also significantly upregulate IL-10 (anti-inflammatory factor) expression and downregulate TNF-α (pro-inflammatory factor) expression. Additionally, the microenvironment, which was established by M2 macrophages, favored the osteogenesis of BMSCs both in vivo and in vitro. These findings show that the GO-HA nanocomposite coating is a promising surface-modification material. Hence, this study provides a reference for the development of next-generation osteoimmunomodulatory biomaterials.

Asunto(s)

Materiales Biocompatibles Revestidos , Durapatita , Grafito , Macrófagos , Células Madre Mesenquimatosas , Oseointegración , Osteogénesis , Oseointegración/efectos de los fármacos , Durapatita/química , Durapatita/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/citología , Animales , Grafito/química , Grafito/farmacología , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Osteogénesis/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Ratones , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Prótesis e Implantes , Inmunomodulación/efectos de los fármacos , Nanocompuestos/química , Células RAW 264.7 , Diferenciación Celular/efectos de los fármacos , Titanio/química , Titanio/farmacología , Masculino

RESUMEN

Porphyromonas gingivalis has been demonstrated to have the strongest association with periodontitis. Within the host, P. gingivalis relies on acquiring iron and heme through the aggregation and lysis of erythrocytes, which are important factors in the growth and virulence of P. gingivalis. Additionally, the excess obtained heme is deposited on the surface of P. gingivalis, protecting the cells from oxidative damage. Based on these biological properties of the interaction between P. gingivalis and erythrocytes, this study developed an erythrocyte membrane nanovesicle loaded with gallium porphyrins to mimic erythrocytes. The nanovesicle can target and adhere with P. gingivalis precisely, being lysed and utilized by P. gingivalis as erythrocytes. Ingested gallium porphyrin replaces iron porphyrin in P. gingivalis, causing intracellular metabolic disruption. Deposited porphyrin generates a large amount of reactive oxygen species (ROS) under blue light, causing oxidative damage, and its lethality is enhanced by bacterial metabolic disruption, synergistically killing P. gingivalis. Our results demonstrate that this strategy can target and inhibit P. gingivalis, reduce its invasion of epithelial cells, and alleviate the progression of periodontitis.

Asunto(s)

Eritrocitos , Periodontitis , Porfirinas , Porphyromonas gingivalis , Porphyromonas gingivalis/efectos de los fármacos , Porphyromonas gingivalis/metabolismo , Porphyromonas gingivalis/química , Periodontitis/microbiología , Periodontitis/tratamiento farmacológico , Periodontitis/patología , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Humanos , Porfirinas/química , Porfirinas/farmacología , Animales , Especies Reactivas de Oxígeno/metabolismo , Galio/química , Galio/farmacología , Ratones , Antibacterianos/farmacología , Antibacterianos/química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología

RESUMEN

Bacterial infections claim millions of lives every year, with the escalating menace of microbial antibiotic resistance compounding this global crisis. Nanozymes, poised as prospective substitutes for antibiotics, present a significant frontier in antibacterial therapy, yet their precise enzymatic origins remain elusive. With the continuous development of nanozymes, the applications of elemental N-modulated nanozymes have spanned multiple fields, including sensing and detection, infection therapy, cancer treatment, and pollutant degradation. The introduction of nitrogen into nanozymes not only broadens their application range but also holds significant importance for the design of catalysts in biomedical research. The synergistic interplay between W and N induces pivotal alterations in electronic configurations, endowing tungsten nitride (WN) with a peroxidase-like functionality. Furthermore, the introduction of N vacancies augments the nanozyme activity, thus amplifying the catalytic potential of WN nanostructures. Rigorous theoretical modeling and empirical validation corroborate the genesis of the enzyme activity. The meticulously engineered WN nanoflower architecture exhibits an exceptional ability in traversing bacterial surfaces, exerting potent bactericidal effects through direct physical interactions. Additionally, the topological intricacies of these nanostructures facilitate precise targeting of generated radicals on bacterial surfaces, culminating in exceptional bactericidal efficacy against both Gram-negative and Gram-positive bacterial strains along with notable inhibition of bacterial biofilm formation. Importantly, assessments using a skin infection model underscore the proficiency of WN nanoflowers in effectively clearing bacterial infections and fostering wound healing. This pioneering research illuminates the realm of pseudoenzyme activity and bacterial capture-killing strategies, promising a fertile ground for the development of innovative, high-performance artificial peroxidases.

Asunto(s)

Antibacterianos , Nitrógeno , Antibacterianos/farmacología , Antibacterianos/química , Nitrógeno/química , Pruebas de Sensibilidad Microbiana , Compuestos de Tungsteno/química , Compuestos de Tungsteno/farmacología , Peroxidasa/metabolismo , Peroxidasa/química , Animales , Tungsteno/química , Tungsteno/farmacología , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Infecciones Bacterianas/tratamiento farmacológico , Ratones , Catálisis , Nanoestructuras/química , Escherichia coli/efectos de los fármacos , Humanos

RESUMEN

Targeting phospholipid biosynthesis, specifically phosphatidylcholine (PC), which is enhanced in tumor cells, has been proven a suitable antitumor strategy. In fact, the overexpression of the choline kinase α1 (ChoKα1) isoform has been found in malignant cells and tumors, thus becoming an excellent antitumor target. ChoKα1 inhibitors are being synthesized at the present that show a large inhibitory activity. Two of them have been chosen in this study as representatives of different structural families: a biscationic biphenyl derivative of thieno[3,2-d]pyrimidinium substituted with a cyclic amine (here referred to as Fa22) and a biscationic biphenyl thioethano derivative of 7-chloro-quinolinium substituted with a pyrrolidinic moiety (here referred to as PL48). However, the potential use of these types of compounds in systemic treatments is hampered because of their low specificity. In fact, to enter the cell and reach their target, these inhibitors use choline transporters and inhibit choline uptake, being that one of the causes of their toxicity. One way to solve this problem could be allowing their entrance into the cells by alternative ways. With this goal, MamC-mediated magnetic nanoparticles (BMNPs), already proven effective drug nanocarriers, have been used to immobilize Fa22 and PL48. The idea is to let BMNPs enter the cell (they enter the cell by endocytosis) carrying these molecules, and, therefore, offering another way in for these compounds. In the present study, we demonstrate that the coupling of Fa22 and PL48 to BMNPs allows these molecules to enter the tumoral cell without completely inhibiting choline uptake, so, therefore, the use of Fa22 and PL48 in these nanoformulations reduces the toxicity compared to that of the soluble drugs. Moreover, the nanoassemblies Fa22-BMNPs and PL48-BMNPs allow the combination of chemotherapy and local hyperthermia therapies for a enhanced cytotoxic effect on the tumoral HepG2 cell line. The consistency of the results, independently of the drug structure, may indicate that this behavior could be extended to other ChoKα1 inhibitors, opening up a possibility for their potential use in clinics.

Asunto(s)

Colina Quinasa , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Materiales Biomiméticos/síntesis química , Proliferación Celular/efectos de los fármacos , Colina Quinasa/antagonistas & inhibidores , Colina Quinasa/metabolismo , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Nanopartículas de Magnetita/química , Estructura Molecular , Relación Estructura-Actividad , Fosfatidilcolinas/química , Fosfatidilcolinas/farmacología

RESUMEN

Implant-associated infections and delayed osseointegration are major challenges for the clinical success of titanium implants. To enhance antibacterial effects and promote early osseointegration, we developed a synergistic photothermal (PTT)/photodynamic (PDT) therapy strategy based on near-infrared (NIR) responsive biomimetic micro/nano titanate/TiO2-X heterostructure coatings (KMNW and NaMNS) in situ constructed on the surface of titanium implants. Specifically, KMNW and NaMNS significantly enhanced photothermal conversion capabilities, achieving localized high temperatures of 48-51 °C and promoting substantial amounts of reactive oxygen species production under 808 nm irradiation. In vitro antibacterial experiments demonstrated that KMNW achieved the highest antibacterial rates against Staphylococcus aureus and Escherichia coli, at 98.78 and 98.33% respectively. Moreover, by mimicking the three-dimensional fibrous network of the extracellular matrix during bone healing, both KMNW and NaMNS markedly promoted the proliferation and osteogenic differentiation of osteoblasts. In vivo implantation studies further confirmed these findings, with KMNW and NaMNS exhibiting superior antibacterial performance under NIR irradiation─94.45% for KMNW and 92.66% for NaMNS. Moreover, KMNW and NaMNS also significantly promoted new bone formation and improved osseointegration in vivo. This study presents a promising PTT/PDT therapeutic strategy for dentistry and orthopedics by employing NIR-responsive biomimetic coatings to combat implant-associated infection and accelerate osseointegration.

Asunto(s)

Antibacterianos , Escherichia coli , Rayos Infrarrojos , Oseointegración , Staphylococcus aureus , Titanio , Titanio/química , Titanio/farmacología , Oseointegración/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Animales , Staphylococcus aureus/efectos de los fármacos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Materiales Biomiméticos/efectos de la radiación , Prótesis e Implantes , Fotoquimioterapia , Ratones , Terapia Fototérmica , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Pruebas de Sensibilidad Microbiana , Osteoblastos/efectos de los fármacos , Osteoblastos/citología , Osteogénesis/efectos de los fármacos

RESUMEN

Accidents and surgical procedures inevitably lead to wounds, presenting clinical challenges such as inflammation and microbial infections that impede the wound-healing process. This study aimed to address these challenges by developing a series of novel wound dressings known as electrospun biomimetic nanofiber membranes. These membranes were prepared using electrostatic spinning technique, incorporating hydroxypropyl-ß-cyclodextrin/dihydromyricetin inclusion complexes. The prepared electrospun biomimetic nanofiber membranes exhibited randomly arranged fiber morphology with average fiber diameters ranging from 200 to 400 nm, resembling the collagen fibers in the native skin. These membranes demonstrated excellent biocompatibility, hemocompatibility, surface hydrophilicity, and wettability, while also releasing dihydromyricetin in a sustained manner. In vitro testing revealed that these membranes, loaded with hydroxypropyl-ß-cyclodextrin/dihydromyricetin inclusion complexes, displayed higher antioxidant potential and inhibitory effects against Staphylococcus aureus and Escherichia coli. Furthermore, these membranes significantly reduced the M1 phenotypic transition in RAW264.7 cells, even when stimulated by lipopolysaccharides, effectively restoring M2 polarization, thereby shortening the inflammatory period. Additionally, the in vivo wound healing effects of these membranes were validated. In conclusion, this study introduces a promising nanofiber membrane with diverse biological properties that holds promise for addressing various crucial aspects of the wound-healing process.

Asunto(s)

Quitosano , Flavonoles , Membranas Artificiales , Nanofibras , Cicatrización de Heridas , Nanofibras/química , Cicatrización de Heridas/efectos de los fármacos , Quitosano/química , Quitosano/farmacología , Animales , Ratones , Flavonoles/farmacología , Flavonoles/química , Células RAW 264.7 , Staphylococcus aureus/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Escherichia coli/efectos de los fármacos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Antioxidantes/farmacología , Antioxidantes/química , Biomimética/métodos , Vendajes

RESUMEN

Impaired wound healing in diabetic wounds is common due to infection, inflammation, less collagen synthesis, and vascularization. Diabetic wound healing in patients is still a challenge and needs an ideal wound dressing to treat and manage diabetic wounds. Herein, an efficacious wound dressing biomaterial was fabricated by cross-linking oxidized isabgol (Oisab) and chitosan (Cs) via trisodium trimetaphosphate and Schiff base bonds. l-Arginine (l-Arg) was incorporated as a bioactive substance in the Oisab + Cs scaffold to promote cell adhesion, cell proliferation, collagen synthesis, and vascularization. The fabricated scaffolds showed microporous networks in the scanning electron microscopy analysis. The scaffold also possessed excellent hemocompatibility. In vitro studies using fibroblasts (L929 and human dermal fibroblast cells) confirmed the cytocompatibility of these scaffolds. The results of the in vivo chicken chorioallantoic membrane assay confirmed the proangiogenic activity of the Oisab + Cs + l-Arg scaffolds. The wound-healing potential of these scaffolds was studied in streptozotocin-induced diabetic rats. This in vivo study showed that the period of epithelialization in the Oisab + Cs + l-Arg scaffold-treated wounds was 21.67 ± 1.6 days, which was significantly faster than the control (30.33 ± 2.5 days). Histological and immunohistochemical studies showed that the Oisab + Cs + l-Arg scaffolds significantly accelerated the rate of wound contraction by reducing inflammation, improving collagen synthesis, and promoting neovascularization. These findings suggest that the Oisab + Cs + l-Arg scaffolds could be beneficial in treating diabetic wounds in clinical applications.

Asunto(s)

Arginina , Quitosano , Colágeno , Diabetes Mellitus Experimental , Ensayo de Materiales , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Quitosano/química , Quitosano/farmacología , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/tratamiento farmacológico , Ratas , Colágeno/química , Arginina/química , Arginina/farmacología , Andamios del Tejido/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Humanos , Masculino , Tamaño de la Partícula , Neovascularización Fisiológica/efectos de los fármacos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Materiales Biomiméticos/síntesis química , Ratones , Ratas Sprague-Dawley , Oxidación-Reducción

RESUMEN

In recent years, overuse of antibiotics has led to emerging antibiotic-resistant strains of bacteria. Consequently, creating new, highly productive antibacterial agents is crucial. In this work, we synthesized copper-aluminum-zinc layered double hydroxide (Co-Al-Zn LDH) and modified it using adenosine triphosphate. After characterization, the enzyme-like activity of the prepared particles was evaluated. The results indicated peroxidase-mimic performance of ATP/Co-Al-Zn LDH with Km values of 0.38 mM and 1.69 mM for TMB (3,3',5,5'-tetramethylbenzidine) and hydrogen peroxide (H2O2), respectively, which were lower than that of horseradish peroxidase. The highest peroxidase-like activity of ATP/Co-Al-Zn LDH was achieved at 20 °C, pH 4, with a 1.02 mg/mL catalyst, 231 µM TMB, and 1.9 mM H2O2. The bactericidal activity of the developed nanozyme was studied against E. coli and S. aureus. The peroxidase-mimic nanozyme decomposes H2O2 and generates free radicals to kill bacteria in vitro. The minimum inhibitory concentration (MIC) of ATP/Co-Al-Zn LDH was 15 µg/mL and 20 µg/mL for S. aureus and E. coli, respectively. The morphological characteristics of the nanozyme-treated bacterial cells showed dramatic changes in bacterial morphology. Our results revealed higher antibacterial activity of ATP/Co-Al-Zn LDH against S. aureus. Therefore, the developed nanozyme could serve as a substitute for conventional antibiotics.

Asunto(s)

Adenosina Trifosfato , Antibacterianos , Peróxido de Hidrógeno , Peroxidasa , Staphylococcus aureus , Zinc , Antibacterianos/farmacología , Antibacterianos/química , Adenosina Trifosfato/metabolismo , Staphylococcus aureus/efectos de los fármacos , Peroxidasa/metabolismo , Zinc/química , Zinc/farmacología , Peróxido de Hidrógeno/química , Escherichia coli/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Aluminio/química , Aluminio/farmacología , Cobre/química , Cobre/farmacología , Catálisis , Hidróxidos/química , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Concentración de Iones de Hidrógeno , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología