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1.
Molecules ; 29(9)2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38731407

RESUMEN

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.


Asunto(s)
Antibacterianos , Nanoestructuras , Propiedades de Superficie , Antibacterianos/farmacología , Antibacterianos/química , Nanoestructuras/química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Humanos , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/prevención & control
2.
ACS Appl Mater Interfaces ; 16(19): 25101-25112, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38691046

RESUMEN

The evolution of nano-drug delivery systems addresses the limitations of conventional cancer treatments with stimulus-responsive nanomaterial-based delivery systems presenting temporal and spatial advantages. Among various nanomaterials, boron nitride nanoparticles (BNNs) demonstrate significant potential in drug delivery and cancer treatment, providing a high drug loading capacity, multifunctionality, and low toxicity. However, the challenge lies in augmenting nanomaterial accumulation exclusively within tumors while preserving healthy tissues. To address this, we introduce a novel approach involving cancer cell membrane-functionalized BNNs (CM-BIDdT) for the codelivery of doxorubicin (Dox) and indocyanine green to treat homologous tumor. The cancer cell membrane biomimetic CM-BIDdT nanoparticles possess highly efficient homologous targeting capabilities toward tumor cells. The surface modification with acylated TAT peptides (dTAT) further enhances the nanoparticle intracellular accumulation. Consequently, CM-BIDdT nanoparticles, responsive to the acidic tumor microenvironment, hydrolyze amide bonds, activate the transmembrane penetrating function, and achieve precise targeting with substantial accumulation at the tumor site. Additionally, the photothermal effect of CM-BIDdT under laser irradiation not only kills cells through thermal ablation but also destroys the membrane on the surface of the nanoparticles, facilitating Dox release. Therefore, the fabricated CM-BIDdT nanoparticles orchestrate chemo-photothermal combination therapy and effectively inhibit tumor growth with minimal adverse effects, holding promise as a new modality for synergistic cancer treatment.


Asunto(s)
Compuestos de Boro , Doxorrubicina , Verde de Indocianina , Nanopartículas , Doxorrubicina/química , Doxorrubicina/farmacología , Verde de Indocianina/química , Verde de Indocianina/farmacología , Compuestos de Boro/química , Compuestos de Boro/farmacología , Animales , Humanos , Ratones , Nanopartículas/química , Línea Celular Tumoral , Terapia Fototérmica , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/terapia , Antineoplásicos/química , Antineoplásicos/farmacología , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/química , Ratones Endogámicos BALB C , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos
3.
Int J Nanomedicine ; 19: 3957-3972, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38711614

RESUMEN

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.


Asunto(s)
Cobre , Doxorrubicina , Grafito , Estructuras Metalorgánicas , Neoplasias de la Próstata , Masculino , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Doxorrubicina/farmacología , Doxorrubicina/química , Animales , Humanos , Línea Celular Tumoral , Cobre/química , Cobre/farmacología , Grafito/química , Grafito/farmacología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Ratones , Liberación de Fármacos , Especies Reactivas de Oxígeno/metabolismo , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Ratones Desnudos , Nanopartículas/química , Antineoplásicos/farmacología , Antineoplásicos/química , Portadores de Fármacos/química , Ensayos Antitumor por Modelo de Xenoinjerto
4.
ACS Appl Bio Mater ; 7(5): 2862-2871, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38699864

RESUMEN

Mosquito-borne viruses are a major worldwide health problem associated with high morbidity and mortality rates and significant impacts on national healthcare budgets. The development of antiviral drugs for both the treatment and prophylaxis of these diseases is thus of considerable importance. To address the need for therapeutics with antiviral activity, a library of heparan sulfate mimetic polymers was screened against dengue virus (DENV), Yellow fever virus (YFV), Zika virus (ZIKV), and Ross River virus (RRV). The polymers were prepared by RAFT polymerization of various acidic monomers with a target MW of 20 kDa (average Mn ∼ 27 kDa by GPC). Among the polymers, poly(SS), a homopolymer of sodium styrenesulfonate, was identified as a broad spectrum antiviral with activity against all the tested viruses and particularly potent inhibition of YFV (IC50 = 310 pM). Our results further uncovered that poly(SS) exhibited a robust inhibition of ZIKV infection in both mosquito and human cell lines, which points out the potential functions of poly(SS) in preventing mosquito-borne viruses associated diseases by blocking viral transmission in their mosquito vectors and mitigating viral infection in patients.


Asunto(s)
Antivirales , Heparitina Sulfato , Polímeros , Antivirales/farmacología , Antivirales/química , Antivirales/síntesis química , Heparitina Sulfato/química , Heparitina Sulfato/farmacología , Animales , Humanos , Polímeros/química , Polímeros/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Culicidae/efectos de los fármacos , Culicidae/virología , Pruebas de Sensibilidad Microbiana , Ensayo de Materiales , Tamaño de la Partícula , Línea Celular , Estructura Molecular , Chlorocebus aethiops , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Virus Zika/efectos de los fármacos
5.
J Nanobiotechnology ; 22(1): 250, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38750519

RESUMEN

The complexity of repairing large segment defects and eradicating residual tumor cell puts the osteosarcoma clinical management challenging. Current biomaterial design often overlooks the crucial role of precisely regulating innervation in bone regeneration. Here, we develop a Germanium Selenium (GeSe) co-doped polylactic acid (PLA) nanofiber membrane-coated tricalcium phosphate bioceramic scaffold (TCP-PLA/GeSe) that mimics the bone-periosteum structure. This biomimetic scaffold offers a dual functionality, combining piezoelectric and photothermal conversion capabilities while remaining biodegradable. When subjected to ultrasound irradiation, the US-electric stimulation of TCP-PLA/GeSe enables spatiotemporal control of neurogenic differentiation. This feature supports early innervation during bone formation, promoting early neurogenic differentiation of Schwann cells (SCs) by increasing intracellular Ca2+ and subsequently activating the PI3K-Akt and Ras signaling pathways. The biomimetic scaffold also demonstrates exceptional osteogenic differentiation potential under ultrasound irradiation. In rabbit model of large segment bone defects, the TCP-PLA/GeSe demonstrates promoted osteogenesis and nerve fibre ingrowth. The combined attributes of high photothermal conversion capacity and the sustained release of anti-tumor selenium from the TCP-PLA/GeSe enable the synergistic eradication of osteosarcoma both in vitro and in vivo. This strategy provides new insights on designing advanced biomaterials of repairing large segment bone defect and osteosarcoma.


Asunto(s)
Regeneración Ósea , Fosfatos de Calcio , Osteogénesis , Osteosarcoma , Andamios del Tejido , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Animales , Regeneración Ósea/efectos de los fármacos , Andamios del Tejido/química , Conejos , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Osteogénesis/efectos de los fármacos , Poliésteres/química , Humanos , Diferenciación Celular/efectos de los fármacos , Neoplasias Óseas/patología , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/terapia , Línea Celular Tumoral , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Células de Schwann/efectos de los fármacos , Nanofibras/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Selenio/química , Selenio/farmacología
6.
J Nanobiotechnology ; 22(1): 263, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760755

RESUMEN

The prevalence of cardiovascular diseases continues to be a challenge for global health, necessitating innovative solutions. The potential of high-density lipoprotein (HDL) mimetic nanotherapeutics in the context of cardiovascular disease and the intricate mechanisms underlying the interactions between monocyte-derived cells and HDL mimetic showing their impact on inflammation, cellular lipid metabolism, and the progression of atherosclerotic plaque. Preclinical studies have demonstrated that HDL mimetic nanotherapeutics can regulate monocyte recruitment and macrophage polarization towards an anti-inflammatory phenotype, suggesting their potential to impede the progression of atherosclerosis. The challenges and opportunities associated with the clinical application of HDL mimetic nanotherapeutics, emphasize the need for additional research to gain a better understanding of the precise molecular pathways and long-term effects of these nanotherapeutics on monocytes and macrophages to maximize their therapeutic efficacy. Furthermore, the use of nanotechnology in the treatment of cardiovascular diseases highlights the potential of nanoparticles for targeted treatments. Moreover, the concept of theranostics combines therapy and diagnosis to create a selective platform for the conversion of traditional therapeutic medications into specialized and customized treatments. The multifaceted contributions of HDL to cardiovascular and metabolic health via highlight its potential to improve plaque stability and avert atherosclerosis-related problems. There is a need for further research to maximize the therapeutic efficacy of HDL mimetic nanotherapeutics and to develop targeted treatment approaches to prevent atherosclerosis. This review provides a comprehensive overview of the potential of nanotherapeutics in the treatment of cardiovascular diseases, emphasizing the need for innovative solutions to address the challenges posed by cardiovascular diseases.


Asunto(s)
Enfermedades Cardiovasculares , Lipoproteínas HDL , Macrófagos , Monocitos , Humanos , Lipoproteínas HDL/química , Lipoproteínas HDL/metabolismo , Lipoproteínas HDL/farmacología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Animales , Enfermedades Cardiovasculares/tratamiento farmacológico , Monocitos/efectos de los fármacos , Nanopartículas/química , Aterosclerosis/tratamiento farmacológico , Placa Aterosclerótica/tratamiento farmacológico , Nanomedicina/métodos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología
7.
Carbohydr Polym ; 338: 122204, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38763712

RESUMEN

This study presents the development and characterization of a novel double-network self-healing hydrogel based on N-carboxyethyl chitosan (CEC) and oxidized dextran (OD) with the incorporation of crosslinked collagen (CEC-OD/COL-GP) to enhance its biological and physicochemical properties. The hydrogel formed via dynamic imine bond formation exhibited efficient self-healing within 30 min, and a compressive modulus recovery of 92 % within 2 h. In addition to its self-healing ability, CEC-OD/COL-GP possesses unique physicochemical characteristics including transparency, injectability, and adhesiveness to various substrates and tissues. Cell encapsulation studies confirmed the biocompatibility and suitability of the hydrogel as a cell-culture scaffold, with the presence of a collagen network that enhances cell adhesion, spreading, long-term cell viability, and proliferation. Leveraging their unique properties, we engineered assemblies of self-healing hydrogel modules for controlled spatiotemporal drug delivery and constructed co-culture models that simulate angiogenesis in tumor microenvironments. Overall, the CEC-OD/COL-GP hydrogel is a versatile and promising material for biomedical applications, offering a bottom-up approach for constructing complex structures with self-healing capabilities, controlled drug release, and support for diverse cell types in 3D environments. This hydrogel platform has considerable potential for advancements in tissue engineering and therapeutic interventions.


Asunto(s)
Adhesión Celular , Quitosano , Dextranos , Hidrogeles , Hidrogeles/química , Hidrogeles/farmacología , Quitosano/química , Dextranos/química , Humanos , Adhesión Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colágeno/química , Animales , Liberación de Fármacos , Proliferación Celular/efectos de los fármacos , Encapsulación Celular/métodos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Ratones , Biomimética/métodos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Andamios del Tejido/química
8.
J Colloid Interface Sci ; 667: 624-639, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38663278

RESUMEN

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.


Asunto(s)
Glicerol , Magnesio , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Glicerol/química , Glicerol/farmacología , Magnesio/química , Magnesio/farmacología , Ratones , Seda/química , Hidrogeles/química , Hidrogeles/farmacología , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Diabetes Mellitus Experimental/tratamiento farmacológico , Vendajes , Humanos , Ratas , Nanofibras/química , Proliferación Celular/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Masculino , Células Endoteliales de la Vena Umbilical Humana , Celulosa/química , Celulosa/farmacología , Celulosa/análogos & derivados
9.
ACS Appl Bio Mater ; 7(5): 2637-2659, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38687958

RESUMEN

Extensive research has been conducted on the application of nanoparticles in the treatment of cancer and infectious diseases. Due to their exceptional characteristics and flexible structure, they are classified as highly efficient drug delivery systems, ensuring both safety and targeted delivery. Nevertheless, nanoparticles still encounter obstacles, such as biological instability, absence of selectivity, recognition as unfamiliar elements, and quick elimination, which restrict their remedial capacity. To surmount these drawbacks, biomimetic nanotechnology has been developed that utilizes T cell and natural killer (NK) cell membrane-encased nanoparticles as sophisticated methods of administering drugs. These nanoparticles can extend the duration of drug circulation and avoid immune system clearance. During the membrane extraction and coating procedure, the surface proteins of immunological cells are transferred to the biomimetic nanoparticles. Such proteins present on the surface of cells confer several benefits to nanoparticles, including prolonged circulation, enhanced targeting, controlled release, specific cellular contact, and reduced in vivo toxicity. This review focuses on biomimetic nanosystems that are derived from the membranes of T cells and NK cells and their comprehensive extraction procedure, manufacture, and applications in cancer treatment and viral infections. Furthermore, potential applications, prospects, and existing challenges in their medical implementation are highlighted.


Asunto(s)
Membrana Celular , Células Asesinas Naturales , Nanopartículas , Neoplasias , Linfocitos T , Humanos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/efectos de los fármacos , Nanopartículas/química , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Membrana Celular/química , Virosis/tratamiento farmacológico , Antineoplásicos/química , Antineoplásicos/farmacología , Animales , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Tamaño de la Partícula , Ensayo de Materiales , Antivirales/química , Antivirales/farmacología , Antivirales/uso terapéutico
10.
Acta Biomater ; 180: 183-196, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38604465

RESUMEN

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.


Asunto(s)
Implantes Absorbibles , Materiales Biocompatibles Revestidos , Magnesio , Nanocompuestos , Stents , Animales , Conejos , Magnesio/química , Magnesio/farmacología , Nanocompuestos/química , Corrosión , Materiales Biocompatibles Revestidos/química , Materiales Biocompatibles Revestidos/farmacología , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Incrustaciones Biológicas/prevención & control , Dioxanos/química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Polímeros/química , Polímeros/farmacología , Aleaciones/química , Aleaciones/farmacología
11.
Biol Direct ; 19(1): 30, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38654256

RESUMEN

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.


Asunto(s)
Proteína Morfogenética Ósea 2 , Regeneración Ósea , Osteogénesis , Ratas Sprague-Dawley , Animales , Proteína Morfogenética Ósea 2/metabolismo , Proteína Morfogenética Ósea 2/genética , Ratas , Regeneración Ósea/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Conejos , Estructuras Metalorgánicas/química , Receptores de Transferrina/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Peroxidasa/metabolismo , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Transducción de Señal/efectos de los fármacos , Peróxido de Hidrógeno , Masculino
12.
Colloids Surf B Biointerfaces ; 238: 113909, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38599076

RESUMEN

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.


Asunto(s)
Materiales Biomiméticos , Membrana Celular , Doxorrubicina , Nanopartículas , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Doxorrubicina/farmacología , Doxorrubicina/química , Nanopartículas/química , Carcinoma Nasofaríngeo/tratamiento farmacológico , Carcinoma Nasofaríngeo/patología , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Membrana Celular/química , Membrana Celular/metabolismo , Membrana Celular/efectos de los fármacos , Animales , Neoplasias Nasofaríngeas/tratamiento farmacológico , Neoplasias Nasofaríngeas/patología , Dendrímeros/química , Ratones , Línea Celular Tumoral , Sistemas de Liberación de Medicamentos , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administración & dosificación , Proliferación Celular/efectos de los fármacos , Ratones Desnudos , Ratones Endogámicos BALB C , Biomimética , Tamaño de la Partícula
13.
Int J Biol Macromol ; 268(Pt 1): 131723, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38649072

RESUMEN

Endometrial injury poses a significant challenge in tissue regeneration, with type III collagen (COL III) playing a pivotal role in maintaining endometrial integrity and facilitating repair. Our study explored the utility of recombinant human type III collagen (RHC) as an intervention for endometrial damage. To address the challenges associated with the inherent instability and rapid degradation of COL III in vivo, we developed an RHC-HA hydrogel by conjugating RHC with hyaluronic acid (HA), thus ensuring a more stable and sustained delivery. Our findings suggested that the RHC-HA hydrogel significantly promoted endometrial regeneration and restored fertility. The hydrogel facilitated prolonged retention of RHC in the uterus, leading to a substantial improvement in the repair process. The synergistic interaction between RHC and HA greatly enhances cell proliferation and adhesion, surpassing the efficacy of HA or RHC alone. Additionally, the RHC-HA hydrogel demonstrated notable anti-fibrotic effects, which are crucial for preventing abnormalities during endometrial healing. These findings suggested that the RHC-HA hydrogel presented a therapeutic strategy in the treatment of uterine endometrial injuries, which may improve female reproductive health.


Asunto(s)
Colágeno Tipo III , Endometrio , Matriz Extracelular , Ácido Hialurónico , Hidrogeles , Proteínas Recombinantes , Regeneración , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Femenino , Endometrio/efectos de los fármacos , Humanos , Hidrogeles/química , Hidrogeles/farmacología , Proteínas Recombinantes/farmacología , Proteínas Recombinantes/administración & dosificación , Animales , Colágeno Tipo III/metabolismo , Matriz Extracelular/efectos de los fármacos , Regeneración/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Materiales Biomiméticos/farmacología , Materiales Biomiméticos/química , Ratas , Adhesión Celular/efectos de los fármacos
14.
ACS Nano ; 18(18): 11753-11768, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38649866

RESUMEN

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.


Asunto(s)
Enfermedad de Alzheimer , Secretasas de la Proteína Precursora del Amiloide , Ácido Aspártico Endopeptidasas , Materiales Biomiméticos , Terapia Genética , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/metabolismo , Animales , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Secretasas de la Proteína Precursora del Amiloide/genética , Ratones , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Ácido Aspártico Endopeptidasas/genética , Ácido Aspártico Endopeptidasas/metabolismo , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/química , Técnicas de Transferencia de Gen , Microglía/metabolismo , Microglía/efectos de los fármacos , Microglía/patología , ARN Interferente Pequeño/química , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/farmacología , Humanos , Liposomas/química , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Biomimética , Exosomas/metabolismo , Exosomas/química , Receptores Inmunológicos/metabolismo , Receptores Inmunológicos/genética
15.
Nanoscale ; 16(18): 8708-8738, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38634521

RESUMEN

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.


Asunto(s)
Membrana Celular , Inmunoterapia , Nanopartículas , Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Membrana Celular/metabolismo , Membrana Celular/química , Nanopartículas/química , Sistemas de Liberación de Medicamentos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Animales , Microambiente Tumoral/efectos de los fármacos
16.
J Nanobiotechnology ; 22(1): 214, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38689291

RESUMEN

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.


Asunto(s)
5'-Nucleotidasa , Adenosina Difosfato , Adenosina , Inmunoterapia , Terapia Fototérmica , Animales , Humanos , Ratones , 5'-Nucleotidasa/antagonistas & inhibidores , Adenosina/química , Adenosina/análogos & derivados , Adenosina/farmacología , Adenosina Difosfato/análogos & derivados , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Biomimética/métodos , Línea Celular Tumoral , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Inmunoterapia/métodos , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Nanopartículas/química , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Terapia Fototérmica/métodos , Puntos Cuánticos/química , Microambiente Tumoral/efectos de los fármacos , Masculino
17.
Biomaterials ; 308: 122561, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38603827

RESUMEN

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.


Asunto(s)
Antifúngicos , Materiales Biomiméticos , Candida albicans , Candidiasis , Nanocompuestos , Nanomedicina Teranóstica , Animales , Nanocompuestos/química , Ratones , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Candidiasis/tratamiento farmacológico , Candidiasis/diagnóstico , Nanomedicina Teranóstica/métodos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Antifúngicos/química , Células RAW 264.7 , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Ratones Endogámicos BALB C , Biomimética/métodos , Humanos , Azul de Metileno/química
18.
Carbohydr Polym ; 336: 122124, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38670755

RESUMEN

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.


Asunto(s)
Materiales Biomiméticos , Polisacáridos , Sulfatos , Ingeniería de Tejidos , Andamios del Tejido , Ingeniería de Tejidos/métodos , Polisacáridos/química , Polisacáridos/farmacología , Andamios del Tejido/química , Humanos , Animales , Sulfatos/química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Biopolímeros/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología
19.
Int J Biol Macromol ; 266(Pt 1): 130999, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38521303

RESUMEN

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.


Asunto(s)
Ingeniería de Tejidos , Ingeniería de Tejidos/métodos , Humanos , Colágeno/química , Materiales Biocompatibles/química , Proliferación Celular/efectos de los fármacos , Andamios del Tejido/química , Biomimética/métodos , Animales , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Movimiento Celular/efectos de los fármacos
20.
Int J Biol Macromol ; 266(Pt 1): 131233, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38554907

RESUMEN

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.


Asunto(s)
Materiales Biomiméticos , Colágeno , Gel de Sílice , Piel Artificial , Andamios del Tejido , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Colágeno/química , Colágeno/farmacología , Porosidad , Ratas , Andamios del Tejido/química , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Gel de Sílice/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Biomimética/métodos , Humanos , Piel/efectos de los fármacos , Piel/lesiones , Masculino
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