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1.
Int J Nanomedicine ; 19: 3957-3972, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711614

RESUMO

Purpose: Current treatment approaches for Prostate cancer (PCa) often come with debilitating side effects and limited therapeutic outcomes. There is urgent need for an alternative effective and safe treatment for PCa. Methods: We developed a nanoplatform to target prostate cancer cells based on graphdiyne (GDY) and a copper-based metal-organic framework (GDY-CuMOF), that carries the chemotherapy drug doxorubicin (DOX) for cancer treatment. Moreover, to provide GDY-CuMOF@DOX with homotypic targeting capability, we coated the PCa cell membrane (DU145 cell membrane, DCM) onto the surface of GDY-CuMOF@DOX, thus obtaining a biomimetic nanoplatform (DCM@GDY-CuMOF@DOX). The nanoplatform was characterized by using transmission electron microscope, atomic force microscope, X-ray diffraction, etc. Drug release behavior, antitumor effects in vivo and in vitro, and biosafety of the nanoplatform were evaluated. Results: We found that GDY-CuMOF exhibited a remarkable capability to load DOX mainly through π-conjugation and pore adsorption, and it responsively released DOX and generated Cu+ in the presence of glutathione (GSH). In vivo experiments demonstrated that this nanoplatform exhibits remarkable cell-killing efficiency by generating lethal reactive oxygen species (ROS) and mediating cuproptosis. In addition, DCM@GDY-CuMOF@DOX effectively suppresses tumor growth in vivo without causing any apparent side effects. Conclusion: The constructed DCM@GDY-CuMOF@DOX nanoplatform integrates tumor targeting, drug-responsive release and combination with cuproptosis and chemodynamic therapy, offering insights for further biomedical research on efficient PCa treatment.


Assuntos
Cobre , Doxorrubicina , Grafite , Estruturas Metalorgânicas , Neoplasias da Próstata , Masculino , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Doxorrubicina/farmacologia , Doxorrubicina/química , Animais , Humanos , Linhagem Celular Tumoral , Cobre/química , Cobre/farmacologia , Grafite/química , Grafite/farmacologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Camundongos , Liberação Controlada de Fármacos , Espécies Reativas de Oxigênio/metabolismo , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Camundongos Nus , Nanopartículas/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Portadores de Fármacos/química , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Molecules ; 29(9)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38731407

RESUMO

The problem of bacterial resistance has become more and more common with improvements in health care. Worryingly, the misuse of antibiotics leads to an increase in bacterial multidrug resistance and the development of new antibiotics has virtually stalled. These challenges have prompted the need to combat bacterial infections with the use of radically different approaches. Taking lessons from the exciting properties of micro-/nano-natural-patterned surfaces, which can destroy cellular integrity, the construction of artificial surfaces to mimic natural functions provides new opportunities for the innovation and development of biomedicine. Due to the diversity of natural surfaces, functional surfaces inspired by natural surfaces have a wide range of applications in healthcare. Nature-inspired surface structures have emerged as an effective and durable strategy to prevent bacterial infection, opening a new way to alleviate the problem of bacterial drug resistance. The present situation of bactericidal and antifouling surfaces with natural and biomimetic micro-/nano-structures is briefly reviewed. In addition, these innovative nature-inspired methods are used to manufacture a variety of artificial surfaces to achieve extraordinary antibacterial properties. In particular, the physical antibacterial effect of nature-inspired surfaces and the functional mechanisms of chemical groups, small molecules, and ions are discussed, as well as the wide current and future applications of artificial biomimetic micro-/nano-surfaces. Current challenges and future development directions are also discussed at the end. In the future, controlling the use of micro-/nano-structures and their subsequent functions will lead to biomimetic surfaces offering great potential applications in biomedicine.


Assuntos
Antibacterianos , Nanoestruturas , Propriedades de Superfície , Antibacterianos/farmacologia , Antibacterianos/química , Nanoestruturas/química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Humanos , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/prevenção & controle
3.
Colloids Surf B Biointerfaces ; 238: 113909, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38599076

RESUMO

Nasopharyngeal carcinoma (NPC) is a common head and neck malignancy, which is characterized by high incidence and aggression with poor diagnosis and limited therapeutic opportunity. The innovative strategy for achieving precise NPC active-targeting drug delivery has emerged as a prominent focus in clinical research. Here, a minimalist cancer cell membrane (CCM) shielded biomimetic nanoparticle (NP) was designed for NPC active-targeting therapy. Chemotherapeutant model drug doxorubicin (DOX) was loaded in polyamidoamine (PAMAM) dendrimer. The PAMAM/DOX (PD) NP was further shielded by human CNE-2 NPC CCM. Characterization results verified that the biomimetic PAMAM/DOX@CCM (abbreviated as PDC) NPs had satisfactory physical properties with high DOX-loading and excellent stability. Cell experiments demonstrated that the CNE-2 membrane-cloaked PDC NPs presented powerful cellular uptake in the sourcing cells by homologous targeting and adhesive interaction. Further in vivo results confirmed that this biomimetic nanoplatform had extended circulation and remarkable tumor-targeting capability, and the PDC NPs effectively suppressed the progression of CNE-2 tumors by systemic administration. This CCM-shielded biomimetic NP displayed a minimalist paradigm nanoplatform for precise NPC therapy, and the strategy of CCM-shielded biomimetic drug delivery system (DDS) has great potential for extensive cancer active-targeting therapy.


Assuntos
Materiais Biomiméticos , Membrana Celular , Doxorrubicina , Nanopartículas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Doxorrubicina/farmacologia , Doxorrubicina/química , Nanopartículas/química , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Membrana Celular/química , Membrana Celular/metabolismo , Membrana Celular/efeitos dos fármacos , Animais , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Dendrímeros/química , Camundongos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Camundongos Nus , Camundongos Endogâmicos BALB C , Biomimética , Tamanho da Partícula
4.
ACS Nano ; 18(18): 11753-11768, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38649866

RESUMO

The association between dysfunctional microglia and amyloid-ß (Aß) is a fundamental pathological event and increases the speed of Alzheimer's disease (AD). Additionally, the pathogenesis of AD is intricate and a single drug may not be enough to achieve a satisfactory therapeutic outcome. Herein, we reported a facile and effective gene therapy strategy for the modulation of microglia function and intervention of Aß anabolism by ROS-responsive biomimetic exosome-liposome hybrid nanovesicles (designated as TSEL). The biomimetic nanovesicles codelivery ß-site amyloid precursor protein cleaving enzyme-1 (BACE1) siRNA (siBACE1) and TREM2 plasmid (pTREM2) gene drug efficiently penetrate the blood-brain barrier and enhance the drug accumulation at AD lesions with the help of exosomes homing ability and angiopep-2 peptides. Specifically, an upregulation of TREM2 expression can reprogram microglia from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype while also restoring its capacity to phagocytose Aß and its nerve repair function. In addition, siRNA reduces the production of Aß plaques at the source by knocking out the BACE1 gene, which is expected to further enhance the therapeutic effect of AD. The in vivo study suggests that TSEL through the synergistic effect of two gene drugs can ameliorate APP/PS1 mice cognitive impairment by regulating the activated microglial phenotype, reducing the accumulation of Aß, and preventing the retriggering of neuroinflammation. This strategy employs biomimetic nanovesicles for the delivery of dual nucleic acids, achieving synergistic gene therapy for AD, thus offering more options for the treatment of AD.


Assuntos
Doença de Alzheimer , Secretases da Proteína Precursora do Amiloide , Ácido Aspártico Endopeptidases , Materiais Biomiméticos , Terapia Genética , Doença de Alzheimer/terapia , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Animais , Secretases da Proteína Precursora do Amiloide/metabolismo , Secretases da Proteína Precursora do Amiloide/genética , Camundongos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Ácido Aspártico Endopeptidases/genética , Ácido Aspártico Endopeptidases/metabolismo , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/química , Técnicas de Transferência de Genes , Microglia/metabolismo , Microglia/efeitos dos fármacos , Microglia/patologia , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/farmacologia , Humanos , Lipossomos/química , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Biomimética , Exossomos/metabolismo , Exossomos/química , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética
5.
Carbohydr Polym ; 336: 122124, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38670755

RESUMO

Sulfated polysaccharides play important roles in tissue engineering applications because of their high growth factor preservation ability and their native-like biological features. There are different sulfated polysaccharides based on different repeating units in the carbohydrate backbone, the position of the sulfate group, and the sulfation degree of the polysaccharide. These led to various sulfated polymers with different negative charge densities and resultant structure-property relationships. Since numerous reports are presented related to sulfated polysaccharide applications in tissue engineering, it is crucial to review the role of effective physicochemical and biological parameters in their usage; as well as their structure-property relationships. Within this review, we focused on the effect of naturally occurring and synthetic sulfated polysaccharides in tissue engineering applications reported in the last years, highlighting the challenges of the scaffold fabrication process, the position, and the degree of sulfate on biomedical activity. Additionally, we discussed their use in numerous in vitro and in vivo model systems.


Assuntos
Materiais Biomiméticos , Polissacarídeos , Sulfatos , Engenharia Tecidual , Alicerces Teciduais , Engenharia Tecidual/métodos , Polissacarídeos/química , Polissacarídeos/farmacologia , Alicerces Teciduais/química , Humanos , Animais , Sulfatos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Biopolímeros/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia
6.
J Colloid Interface Sci ; 667: 624-639, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38663278

RESUMO

Quick scarless healing remains a key issue for diabetic wounds. Here, a stretchable elastomeric hydrogel dressing composed of hydroxyethylcellulose (HEC), silk nano fiber-magnesium ion complex (Mg2+-SNF) and glycerol (Gly) was developed to optimize mechanical niche, anti-inflammatory and angiogenic behavior simultaneously. The composite hydrogel dressing exhibited skin-like elasticity (175.1 ± 23.9 %) and modulus (156.7 ± 2.5 KPa) while Mg2+-SNF complex endowed the dressing with angiogenesis, both favoring quick scarless skin regeneration. In vitro cell studies revealed that the hydrogel dressing stimulated fibroblast proliferation, endothelial cell migration and vessel-like tube formation, and also induced anti-inflammatory behavior of macrophages. In vivo results revealed accelerated healing of diabetic wounds. The improved granulation ingrowth and collagen deposition suggested high quality repair. Both thinner epidermal layer and low collagen I/III ratio of the regenerated skin confirmed scarless tissue formation. This bioactive hydrogel dressing has promising potential to address the multifaceted challenges of diabetic wound management.


Assuntos
Glicerol , Magnésio , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Glicerol/química , Glicerol/farmacologia , Magnésio/química , Magnésio/farmacologia , Camundongos , Seda/química , Hidrogéis/química , Hidrogéis/farmacologia , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Bandagens , Humanos , Ratos , Nanofibras/química , Proliferação de Células/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacos , Masculino , Células Endoteliais da Veia Umbilical Humana , Celulose/química , Celulose/farmacologia , Celulose/análogos & derivados
7.
Acta Biomater ; 180: 183-196, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38604465

RESUMO

The utilization of biodegradable magnesium (Mg) alloys in the fabrication of temporary non-vascular stents is an innovative trend in biomedical engineering. However, the heterogeneous degradation profiles of these biomaterials, together with potential bacterial colonization that could precipitate infectious or stenotic complications, are critical obstacles precluding their widespread clinical application. In pursuit of overcoming these limitations, this study applies the principles of biomimicry, particularly the hydrophobic and anti-fouling characteristics of lotus leaves, to pioneer the creation of nanocomposite coatings. These coatings integrate poly-trimethylene carbonate (PTMC) with covalent organic frameworks (COFs), to modify the stent's surface property. The strategic design of the coating's topography, porosity, and self-polishing capabilities collectively aims to decelerate degradation processes and minimize biological adhesion. The protective qualities of the coatings were substantiated through rigorous testing in both in vitro dynamic bile tests and in vivo New Zealand rabbit choledochal models. Empirical findings from these trials confirmed that the implementation of COF-based nanocomposite coatings robustly fortifies Mg implantations, conferring heightened resistance to both biocorrosion and biofouling as well as improved biocompatibility within bodily environments. The outcomes of this research elucidate a comprehensive framework for the multifaceted strategies against stent corrosion and fouling, thereby charting a visionary pathway toward the systematic conception of a new class of reliable COF-derived surface modifications poised to amplify the efficacy of Mg-based stents. STATEMENT OF SIGNIFICANCE: Biodegradable magnesium (Mg) alloys are widely utilized in temporary stents, though their rapid degradation and susceptibility to bacterial infection pose significant challenges. Our research has developed a nanocomposite coating inspired by the lotus, integrating poly-trimethylene carbonate with covalent organic frameworks (COF). The coating achieved self-polishing property and optimal surface energy on the Mg substrate, which decelerates stent degradation and reduces biofilm formation. Comprehensive evaluations utilizing dynamic bile simulations and implantation in New Zealand rabbit choledochal models reveal that the coating improves the durability and longevity of the stent. The implications of these findings suggest the potential COF-based Mg alloy stent surface treatments and a leap forward in advancing stent performance and endurance in clinical applications.


Assuntos
Implantes Absorvíveis , Materiais Revestidos Biocompatíveis , Magnésio , Nanocompostos , Stents , Animais , Coelhos , Magnésio/química , Magnésio/farmacologia , Nanocompostos/química , Corrosão , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Incrustação Biológica/prevenção & controle , Dioxanos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Polímeros/química , Polímeros/farmacologia , Ligas/química , Ligas/farmacologia
8.
Nanoscale ; 16(18): 8708-8738, 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38634521

RESUMO

Cancer immunotherapy, a burgeoning modality for cancer treatment, operates by activating the autoimmune system to impede the growth of malignant cells. Although numerous immunotherapy strategies have been employed in clinical cancer therapy, the resistance of cancer cells to immunotherapeutic medications and other apprehensions impede the attainment of sustained advantages for most patients. Recent advancements in nanotechnology for drug delivery hold promise in augmenting the efficacy of immunotherapy. However, the efficacy is currently constrained by the inadequate specificity of delivery, low rate of response, and the intricate immunosuppressive tumor microenvironment. In this context, the investigation of cell membrane coated nanoparticles (CMNPs) has revealed their ability to perform targeted delivery, immune evasion, controlled release, and immunomodulation. By combining the advantageous features of natural cell membranes and nanoparticles, CMNPs have demonstrated their unique potential in the realm of cancer immunotherapy. This review aims to emphasize recent research progress and elucidate the underlying mechanisms of CMNPs as an innovative drug delivery platform for enhancing cancer immunotherapy. Additionally, it provides a comprehensive overview of the current immunotherapeutic strategies involving different cell membrane types of CMNPs, with the intention of further exploration and optimization.


Assuntos
Membrana Celular , Imunoterapia , Nanopartículas , Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Membrana Celular/metabolismo , Membrana Celular/química , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Animais , Microambiente Tumoral/efeitos dos fármacos
9.
J Nanobiotechnology ; 22(1): 214, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689291

RESUMO

Combination of tumor immunotherapy with photothermal therapy (PTT) is a feasible tactic to overcome the drawback of immunotherapy such as poor immune response. Via triggering the immunogenic cells death (ICD), PTT can stimulate the activity of immune cells, but meanwhile, the level of adenosine is elevated via the CD73-induced decomposition of ATP which is overexpressed accompanying with the PTT process, resulting in negative feedback to impair the immune stimulation. Herein, we developed a novel biomimetic photothermal nanodrug to specifically block CD73 for inhibition of adenosine production and more efficient priming of the suppressive immune microenvironments. The nanodrug, named as AptEM@CBA, is constructed by encapsulation of photothermal agent black phosphorus quantum dots (BPQDs) and selective CD73 inhibitor α, ß-Methyleneadenosine 5'-diphosphate (AMPCP) in chitosan nanogels, which are further covered with aptamer AS1411 modified erythrocyte membrane (EM) for biomimetic camouflage. With AS1411 induced active targeting and EM induced long blood circulation time, the enrichment of the nanodrug tumor sites is promoted. The photothermal treatment promotes the maturation of dendritic cells. Meanwhile, the release of AMPCP suppress the adenosine generation via CD73 blockade, alleviating the impairment of adenosine to dendritic cells and suppressing regulatory T cells, synergically stimulate the activity of T cells. The combination of CD73 blockade with PTT, not only suppresses the growth of primary implanted tumors, but also boosts strong antitumor immunity to inhibit the growth of distal tumors, providing good potential for tumor photoimmunotherapy.


Assuntos
5'-Nucleotidase , Difosfato de Adenosina , Adenosina , Imunoterapia , Terapia Fototérmica , Animais , Humanos , Camundongos , 5'-Nucleotidase/antagonistas & inibidores , Adenosina/química , Adenosina/análogos & derivados , Adenosina/farmacologia , Difosfato de Adenosina/análogos & derivados , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Biomimética/métodos , Linhagem Celular Tumoral , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Imunoterapia/métodos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Nanopartículas/química , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Terapia Fototérmica/métodos , Pontos Quânticos/química , Microambiente Tumoral/efeitos dos fármacos , Masculino
10.
Biomaterials ; 308: 122561, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38603827

RESUMO

Fungi infection is a serious threat to public health, but an effective antifungal strategy remains a challenge. Herein, a biomimetic nanocomposite with multifunctionalities, including fungi diagnosis, antifungal adhesion, precise fungi elimination, and cytokine sequestration, is constructed for battling Candida albicans (C. albicans) infection. By screening a range of cells, we find that the polarized macrophage cells have the strongest binding tendency toward C. albicans. Thus, their membranes were exfoliated to camouflage UCNPs and then decorated with photosensitizers (methylene blue, MB) and DNA sensing elements. The resulting nanocomposite can tightly bind to fungal surfaces, promote DNA recognition, and squeeze pro-inflammatory cytokines to relieve inflammation. Consequently, this nanocomposite can detect C. albicans with enhanced sensitivity and precisely eliminate fungal cells through photodynamic therapy with minimal phototoxicity because of its switchable fluorescence behavior. The developed nanocomposite with good biocompatibility achieves a satisfactory diagnostic and therapeutic effect in a C. albicans-infected mouse model, which offers a unique approach to fight fungi infection.


Assuntos
Antifúngicos , Materiais Biomiméticos , Candida albicans , Candidíase , Nanocompostos , Nanomedicina Teranóstica , Animais , Nanocompostos/química , Camundongos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Candidíase/tratamento farmacológico , Candidíase/diagnóstico , Nanomedicina Teranóstica/métodos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Antifúngicos/química , Células RAW 264.7 , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Camundongos Endogâmicos BALB C , Biomimética/métodos , Humanos , Azul de Metileno/química
11.
Biol Direct ; 19(1): 30, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38654256

RESUMO

BACKGROUND: Large bone defects pose a clinical treatment challenge; inhibiting transferrin receptor 2 (TfR2), which is involved in iron metabolism, can promote osteogenesis. Iron-based metal-organic frameworks (MOF-Fe) particles not only inhibit TfR2 but also serve as biomimetic catalysts to remove hydrogen peroxide in reactive oxygen species (ROS); excess ROS can disrupt the normal functions of osteoblasts, thereby hindering bone regeneration. This study explored the potential effects of MOF-Fe in increasing osteogenic activity and clearing ROS. METHODS: In vitro experiments were performed to investigate the osteogenic effects of MOF-Fe particles and assess their impact on cellular ROS levels. To further validate the role of MOF-Fe in promoting bone defect repair, we injected MOF-Fe suspensions into the femoral defects of SD rats and implanted MOF-Fe-containing hydrogel scaffolds in rabbit cranial defect models and observed their effects on bone healing. RESULTS: In vitro, the presence of MOF-Fe significantly increased the expression levels of osteogenesis-related genes and proteins compared to those in the control group. Additionally, compared to those in the untreated control group, the cells treated with MOF-Fe exhibited a significantly increased ability to remove hydrogen peroxide from ROS and generate oxygen and water within the physiological pH range. In vivo experiments further confirmed the positive effect of MOF-Fe in promoting bone defect repair. CONCLUSION: This study supports the application of MOF-Fe as an agent for bone regeneration, particularly for mitigating ROS and activating the bone morphogenetic protein (BMP) pathway, demonstrating its potential value.


Assuntos
Proteína Morfogenética Óssea 2 , Regeneração Óssea , Osteogênese , Ratos Sprague-Dawley , Animais , Proteína Morfogenética Óssea 2/metabolismo , Proteína Morfogenética Óssea 2/genética , Ratos , Regeneração Óssea/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Coelhos , Estruturas Metalorgânicas/química , Receptores da Transferrina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Peroxidase/metabolismo , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Peróxido de Hidrogênio , Masculino
12.
Int J Biol Macromol ; 266(Pt 1): 130999, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38521303

RESUMO

Collagen, a key component of extracellular matrix serves as a linchpin for maintaining structural integrity and functional resilience. Concerns over purity and immunogenicity of animal-derived collagens have spurred efforts to develop synthetic collagen-based biomaterials. Despite several collagen mimics, there remains limited exploration of non-immunogenic biomaterials with the capacity for effective self-assembly. To combat the lacuna, collagen like protein (CLP) variants were rationally designed and recombinantly expressed, incorporating human telopeptide sequences (CLP-N and CLP-NC) and bioactive binding sites (CLP-NB). Circular dichroism analyses of the variants confirmed the triple helical conformation, with variations in thermal stability and conformation attributed to the presence of telopeptides at one or both ends of CLP. The variants had propensity to form oligomers, setting the stage for fibrillogenesis. The CLP variants were biocompatible, hemocompatible and supported cell proliferation and migration, particularly CLP-NB with integrin-binding sites. Gene expression indicated a lack of significant upregulation of inflammatory markers, highlighting the non-immunogenic nature of these variants. Lyophilized CLP scaffolds maintained their triple-helical structure and offered favorable biomaterial characteristics. These results accentuate the potential of designed CLP variants in tissue engineering, regenerative medicine and industrial sectors, supporting the development of biocompatible scaffolds and implants for therapeutic and cosmetic purposes.


Assuntos
Engenharia Tecidual , Engenharia Tecidual/métodos , Humanos , Colágeno/química , Materiais Biocompatíveis/química , Proliferação de Células/efeitos dos fármacos , Alicerces Teciduais/química , Biomimética/métodos , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Movimento Celular/efeitos dos fármacos
13.
Int J Biol Macromol ; 266(Pt 1): 131233, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38554907

RESUMO

Full-thickness wounds are severe cutaneous damages with destroyed self-healing function, which need efficient clinical interventions. Inspired by the hierarchical structure of natural skin, we have for the first time developed a biomimetic tri-layered artificial skin (TLAS) comprising silica gel-collagen membrane-collagen porous scaffold for enhanced full-thickness wound healing. The TLAS with the thickness of 3-7 mm displays a hierarchical nanostructure consisting of the top homogeneous silica gel film, the middle compact collagen membrane, and the bottom porous collagen scaffold, exquisitely mimicking the epidermis, basement membrane and dermis of natural skin, respectively. The 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide/N-Hydroxysuccinimide-dehydrothermal (EDC/NHS-DHT) dual-crosslinked collagen composite bilayer, with a crosslinking degree of 79.5 %, displays remarkable biocompatibility, bioactivity, and biosafety with no risk of hemolysis and pyrogen reactions. Notably, the extra collagen membrane layer provides a robust barrier to block the penetration of silica gel into the collagen porous scaffold, leading to the TLAS with enhanced biocompatibility and bioactivity. The full-thickness wound rat model studies have indicated the TLAS significantly facilitates the regeneration of full-thickness defects by accelerating re-epithelization, collagen deposition and migration of skin appendages. The highly biocompatible and bioactive tri-layered artificial skin provides an improved treatment for full-thickness wounds, which has great potential in tissue engineering.


Assuntos
Materiais Biomiméticos , Colágeno , Sílica Gel , Pele Artificial , Alicerces Teciduais , Cicatrização , Cicatrização/efeitos dos fármacos , Animais , Colágeno/química , Colágeno/farmacologia , Porosidade , Ratos , Alicerces Teciduais/química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Sílica Gel/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Biomimética/métodos , Humanos , Pele/efeitos dos fármacos , Pele/lesões , Masculino
14.
Mater Horiz ; 11(8): 1944-1956, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38345779

RESUMO

To date, the reported injectable hydrogels have failed to mimic the fibrous architecture of the extracellular matrix (ECM), limiting their biological effects on cell growth and phenotype. Additionally, they lack the micro-sized pores present within the ECM, which is unfavorable for the facile transport of nutrients and waste. Herein, an injectable ECM-mimetic hydrogel (IEMH) was fabricated by shortening and dispersing Janus fibers capable of self-curling at body temperature into pH 7.4 phosphate buffer solution. The IEMH could be massively prepared through a side-by-side electrospinning process combined with ultraviolet irradiation. The IEMHs with only 5 wt% fibers could undergo sol-gel transition at body temperature to become solid gels with desirable stability, sturdiness, and elasticity and self-healing ability. In addition, they possessed notable pseudoplasticity, which is beneficial to injection at room temperature. The results obtained from characterization analysis via scanning electron microscopy, total internal reflection fluorescence microscopy, nuclear magnetic resonance spectroscopy, and Fourier-transform infrared spectroscopy indicate that their sol-gel transition under physiological conditions stems from the synergistic action of the tight entanglements between thermally-induced self-curling fibers and the hydrophobic interaction between the fibers. An MTT assay using C2C12 myoblast cells was performed to examine the in vitro cytotoxicity of IEMHs for biomedical applications, and the cell viability was found to be more than 95%.


Assuntos
Matriz Extracelular , Hidrogéis , Matriz Extracelular/química , Hidrogéis/química , Hidrogéis/farmacologia , Animais , Camundongos , Linhagem Celular , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia
15.
Adv Healthc Mater ; 13(12): e2303134, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38348511

RESUMO

The effective repair of large bone defects remains a major challenge due to its limited self-healing capacity. Inspired by the structure and function of the natural periosteum, an electrospun biomimetic periosteum is constructed to programmatically promote bone regeneration using natural bone healing mechanisms. The biomimetic periosteum is composed of a bilayer with an asymmetric structure in which an aligned electrospun poly(ε-caprolactone)/gelatin/deferoxamine (PCL/GEL/DFO) layer mimics the outer fibrous layer of the periosteum, while a random coaxial electrospun PCL/GEL/aspirin (ASP) shell and PCL/silicon nanoparticles (SiNPs) core layer mimics the inner cambial layer. The bilayer controls the release of ASP, DFO, and SiNPs to precisely regulate the inflammatory, angiogenic, and osteogenic phases of bone repair. The random coaxial inner layer can effectively antioxidize, promoting cell recruitment, proliferation, differentiation, and mineralization, while the aligned outer layer can promote angiogenesis and prevent fibroblast infiltration. In particular, different stages of bone repair are modulated in a rat skull defect model to achieve faster and better bone regeneration. The proposed biomimetic periosteum is expected to be a promising candidate for bone defect healing.


Assuntos
Materiais Biomiméticos , Regeneração Óssea , Periósteo , Poliésteres , Regeneração Óssea/efeitos dos fármacos , Animais , Periósteo/efeitos dos fármacos , Ratos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Poliésteres/química , Ratos Sprague-Dawley , Desferroxamina/farmacologia , Desferroxamina/química , Gelatina/química , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Preparações de Ação Retardada/farmacocinética , Osteogênese/efeitos dos fármacos , Crânio/efeitos dos fármacos , Crânio/lesões , Masculino , Nanopartículas/química , Engenharia Tecidual/métodos , Diferenciação Celular/efeitos dos fármacos , Alicerces Teciduais/química
16.
Int J Biol Macromol ; 260(Pt 2): 129514, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38237825

RESUMO

Electrospun biomimetic materials based on polyester of natural origin poly-3-hudroxybutyrate (PHB) modified with hemin (Hmi) and fibrinogen (Fbg) represent a great interest and are potentially applicable in various fields. Here, we describe formulation of the new fibrous PHB-Fbg and PHB-Hmi-Fbg materials with complex structure for biomedical application. The average diameter of the fibers was 3.5 µm and 1.8 µm respectively. Hmi presence increased porosity from 80 % to 94 %, significantly reduced the number of defects, ensured the formation of a larger number of open pores, and improved mechanical properties. Hmi presence significantly improved the molding properties of the material. Hmi facilitated effective Fbg adsorption on the of the PHB wound-healing material, ensuring uniform localization of the protein on the surface of the fibers. Next, we evaluated cytocompatibility, cell behavior, and open wound healing in mice. The results demonstrated that PHB-Fbg and PHB-Hmi-Fbg electrospun materials had pronounced properties and may be promising for early-stage wound healing - the PHB-Hmi-Fbg sample accelerated wound closure by 35 % on the 3rd day, and PHB-Hmi showed 45 % more effective wound closure on the 15th day.


Assuntos
Materiais Biomiméticos , Hemostáticos , Camundongos , Animais , Fibrinogênio , Cicatrização , Materiais Biomiméticos/farmacologia , Poliésteres/química
17.
Adv Mater ; 36(10): e2210455, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36854170

RESUMO

Along with the rapid development and ever-deepening understanding of nanoscience and nanotechnology, nanomaterials hold promise to mimic the highly evolved biological exquisite nanostructures and sophisticated functions. Here, inspired by the ubiquitous antibacterial nanostructures on the wing surfaces of some insects, a NiCo2 O4 nanozyme with self-adaptive hierarchical nanostructure is developed that can capture bacteria of various morphotypes via the physico-mechanical interaction between the nanostructure and bacteria. Moreover, the developed biomimetic nanostructure further exhibits superior peroxidase-like catalytic activity, which can catalytically generate highly toxic reactive oxygen species that disrupt bacterial membranes and induce bacterial apoptosis. Therefore, the mechano-catalytic coupling property of this NiCo2 O4 nanozyme allows for an extensive and efficient antibacterial application, with no concerns of antimicrobial resistance. This work suggests a promising strategy for the rational design of advanced antibacterial materials by mimicking biological antibiosis.


Assuntos
Materiais Biomiméticos , Nanoestruturas , Animais , Materiais Biomiméticos/farmacologia , Materiais Biomiméticos/química , Peroxidases , Oxirredutases , Antibacterianos/farmacologia , Nanoestruturas/química
18.
Antiviral Res ; 217: 105673, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37478917

RESUMO

Human cytomegalovirus (HCMV) can cause serious diseases in immunocompromised patients. Use of current antivirals is limited by their adverse effects and emergence of drug resistance mutations. Thus, new drugs are an urgent need. The terminase complex (pUL56-pUL89-pUL51) represents a target of choice for new antivirals development. pUL51 was shown to be crucial for the cleavage of concatemeric HCMV DNA and viral replication. Its C-terminal part plays a critical role for the terminase complex assembly. However, no interaction domain is clearly identified. Sequence comparison of herpesvirus homologs and protein modelling were performed on pUL51. Importance of a putative interaction domain is validated by the generation of recombinant viruses with specific alanine substitutions of amino acids implicated in the domain. We identified a Leucine-Zipper (LZ) domain involving the leucine residues L126-X6-L133-X6-L140-X6-L147 in C-terminal part of pUL51. These leucines are crucial for viral replication, suggesting the significance for pUL51 structure and function. A mimetic-peptide approach has been used and tested in antiviral assays to validate the interaction domain as a new therapeutic target. Cytotoxicity was evaluated by LDH release measurement. The peptide TAT-HK29, homologous to the pUL51-LZ domain, inhibits HCMV replication by 27% ± 9% at 1.25 µM concentration without cytotoxicity. Our results highlight the importance of a leucine zipper domain in the C-terminal part of pUL51 involving leucines L126, L133, L140 and L147. We also confirm the potential of mimetic peptides to inhibit HCMV replication and the importance to target interaction domains to develop antiviral agents.


Assuntos
Antivirais , Materiais Biomiméticos , Citomegalovirus , Endodesoxirribonucleases , Zíper de Leucina , Proteínas Virais , Replicação Viral , Replicação Viral/efeitos dos fármacos , Citomegalovirus/efeitos dos fármacos , Antivirais/química , Antivirais/farmacologia , Proteínas Virais/antagonistas & inibidores , Proteínas Virais/química , Proteínas Virais/genética , Desenvolvimento de Medicamentos , Endodesoxirribonucleases/antagonistas & inibidores , Endodesoxirribonucleases/química , Humanos , Peptídeos/química , Peptídeos/farmacologia , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia
19.
Arterioscler Thromb Vasc Biol ; 43(8): e291-e302, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37317849

RESUMO

The ECM (extracellular matrix) is a 3-dimensional network that supports cellular responses and maintains structural tissue integrity in healthy and pathological conditions. The interactions between ECM and cells trigger signaling cascades that lead to phenotypic changes and structural and compositional turnover of the ECM, which in turn regulates vascular cell behavior. Hydrogel biomaterials are a powerful platform for basic and translational studies and clinical applications due to their high swelling capacity and exceptional versatility in compositions and properties. This review highlights recent developments and uses of engineered natural hydrogel platforms that mimic the ECM and present defined biochemical and mechanical cues for vascularization. Specifically, we focus on modulating vascular cell stimulation and cell-ECM/cell-cell interactions in the microvasculature that are the established biomimetic microenvironment.


Assuntos
Materiais Biomiméticos , Matriz Extracelular , Hidrogéis , Microvasos , Neovascularização Fisiológica , Engenharia Tecidual , Hidrogéis/química , Hidrogéis/farmacologia , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/fisiologia , Neovascularização Fisiológica/efeitos dos fármacos , Neovascularização Fisiológica/genética , Neovascularização Fisiológica/fisiologia , Microvasos/efeitos dos fármacos , Microvasos/fisiologia , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Humanos , Engenharia Tecidual/métodos , Alicerces Teciduais , Técnicas de Transferência de Genes , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Animais
20.
Curr Top Med Chem ; 23(10): 907-920, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37102484

RESUMO

Due to their unique biological functionality, nanocarriers can be designed to deliver various anti-tumor drugs in vivo, which has a wide and important application prospect in the field of tumor therapy. However, poor biosafety, short blood circulation time, and weak targeting ability still limit the application of nanoparticles in tumor therapy. In recent years, with the development of biomedicine, the biomimetic technology-based biomembrane-mediated drug delivery system is expected to achieve a breakthrough in tumor-targeted therapy due to low immunogenicity, tumor targeting, the adjustability and versatility of intelligent nanocarrier design. This paper mainly reviews the research process of different types of the cell membrane (erythrocyte membrane, cancer cell membrane, bacterial membrane, stem cell membrane, and hybrid membrane)-camouflaged nanoparticles in tumor therapy, as well as the challenges and development prospects in clinical application.


Assuntos
Antineoplásicos , Materiais Biomiméticos , Nanopartículas , Neoplasias , Humanos , Biomimética , Materiais Biomiméticos/farmacologia , Membrana Celular , Membrana Eritrocítica/patologia , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias/patologia , Sistemas de Liberação de Medicamentos , Nanopartículas/uso terapêutico
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