RESUMEN

Copper-catalyzed click chemistry offers creative strategies for activation of therapeutics without disrupting biological processes. Despite tremendous efforts, current copper catalysts face fundamental challenges in achieving high efficiency, atom economy, and tissue-specific selectivity. Herein, we develop a facile "mix-and-match synthetic strategy" to fabricate a biomimetic single-site copper-bipyridine-based cerium metal-organic framework (Cu/Ce-MOF@M) for efficient and tumor cell-specific bioorthogonal catalysis. This elegant methodology achieves isolated single-Cu-site within the MOF architecture, resulting in exceptionally high catalytic performance. Cu/Ce-MOF@M favors a 32.1-fold higher catalytic activity than the widely used MOF-supported copper nanoparticles at single-particle level, as first evidenced by single-molecule fluorescence microscopy. Furthermore, with cancer cell-membrane camouflage, Cu/Ce-MOF@M demonstrates preferential tropism for its parent cells. Simultaneously, the single-site CuII species within Cu/Ce-MOF@M are reduced by upregulated glutathione in cancerous cells to CuI for catalyzing the click reaction, enabling homotypic cancer cell-activated in situ drug synthesis. Additionally, Cu/Ce-MOF@M exhibits oxidase and peroxidase mimicking activities, further enhancing catalytic cancer therapy. This study guides the reasonable design of highly active heterogeneous transition-metal catalysts for targeted bioorthogonal reactions.

Asunto(s)

Materiales Biomiméticos , Cobre , Humanos , Cobre/química , Materiales Biomiméticos/química , Catálisis , Estructuras Metalorgánicas/química , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Cerio/química , Línea Celular Tumoral , Animales , Química Clic/métodos , Biomimética/métodos , Ratones

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

A thermoresponsive molecularly imprinted hydrogel sensor was constructed for the specific selective recognition of enterovirus 71 (EV71). Due to the introduction of the thermosensitive monomer N-isopropylacrylamide (NIPAM), when the imprinted hydrogel is incubated with the virus at 37℃, the surface specific imprinting cavity will specifically recognize and capture the target virus EV71. When the temperature rises to 45℃, the combined EV71 is rapidly released due to changes in the shape and function of the imprinted sites. The MIP hydrogel-based viral sensor developed recognized, captured, and released the target virus in a non-invasive way. The imprinting factor of the target virus was 5.2, suggesting high selectivity, and the detection limit was 7.1 fM, suggesting high sensitivity. Detection was rapid, as adsorption equilibrium was achieved within 30 min. This method provides a new sustainable avenue for the simple and rapid detection of viruses.

Asunto(s)

Enterovirus Humano A , Hidrogeles , Impresión Molecular , Enterovirus Humano A/aislamiento & purificación , Hidrogeles/química , Límite de Detección , Temperatura , Polímeros Impresos Molecularmente/química , Materiales Biomiméticos/química , Acrilamidas/química , Humanos

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

Nanozymes offer many advantages such as good stability and high catalytic activity, but their selectivity is lower than that of enzymes. This is because most of enzymes have a protein component (apoenzyme) for substrate affinity to enhance selectivity and a non-protein element (coenzyme) for catalytic activity to improve sensitivity. The synergy between molecularly imprinted polymers (MIPs) and nanozymes can mimic natural enzymes, with MIP acting as the apoenzyme and nanozyme as the coenzyme. Despite researchers' attempts to associate MIPs with nanozymes, the full potential of this combination remains not well explored. This study addresses this gap by integrating Fe3O4-Lys-Cu nanozymes with peroxidase-like catalytic activities within appropriate MIPs for L-DOPA and dopamine. The catalytic performance of the nanozyme was improved by the presence of Cu in Fe3O4-Lys-Cu and further enhanced by MIP. Indeed, the exploration of the pre-concentration property of MIP has increased twenty-fold the catalytic activity of the nanozyme. Moreover, this synergistic combination facilitated the template removal process during MIP production by reducing the extraction time from several hours to just 1 min thanks to the addition of co-substrates which trigger the reaction with nanozyme and release the template. Overall, the synergistic combination of MIPs and nanozymes offers a promising avenue for the design of artificial enzymes.

Asunto(s)

Técnicas Biosensibles , Cobre , Dopamina , Polímeros Impresos Molecularmente , Técnicas Biosensibles/métodos , Polímeros Impresos Molecularmente/química , Cobre/química , Catálisis , Dopamina/química , Levodopa/química , Materiales Biomiméticos/química , Impresión Molecular

RESUMEN

Carbonic anhydrase (CA) plays a crucial role in the CO2 capture processes by catalyzing the hydration of CO2. In this study, we synthesized a bioinspired carbonic anhydrase Zn-MOF (metal-organic framework) incorporating 2-aminoimidazole and Zn2+ as initial constituents. The synthesized Zn-MOF exhibited promising potential for efficiently catalyzing the CO2 hydration. Structural analyses such as SEM, XRD, and BET confirmed that the Zn-MOF crystal consisted of stacked grains with an average size of approximately 36 nm, forming a micron-sized spherical structure. Functionally, Zn-MOF exhibited effective catalytic activity toward both CO2 hydration and ester hydrolysis. The introduction of amino groups significantly enhanced the esterase activity of Zn-MOF to 0.28 U/mg at ambient temperature, which was twice that of ZIF-8. Furthermore, the introduction of amino groups resulted in remarkable hydrothermal stability, with the esterase activity reaching 0.72 U/mg after undergoing hydrothermal treatment at 80 °C for 12 h. Additionally, Zn-MOF exhibited enhanced capability in CO2 hydration at a pH value exceeding 8.5. After six repeated uses, ZIF-8 and Zn-MOF retained approximately 68 and 65% of their initial enzyme activity, respectively, underscoring the potential practical applicability of Zn-MOF in industrial CO2 capture processes. This work showcases the development of a novel Zn-MOF crystal as an efficient CA mimic, effectively emulating the active sites of natural CA using 2-aminoimidazole as a coordinating ligand for Zn2+ coordination. These findings not only advance the field of innovative enzyme mimics but also pave the way for further exploration of industrial CO2 capture catalysts.

Asunto(s)

Dióxido de Carbono , Anhidrasas Carbónicas , Imidazoles , Zinc , Anhidrasas Carbónicas/metabolismo , Anhidrasas Carbónicas/química , Imidazoles/química , Zinc/química , Dióxido de Carbono/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/síntesis química , Materiales Biomiméticos/química , Materiales Biomiméticos/síntesis química , Catálisis , Esterasas/química , Esterasas/metabolismo

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

Protein-based enzymes are among the most efficient catalysts on our planet. A common feature of protein enzymes is that all catalytic amino acids occupy a limited, narrow space and face each other. In this study, we created a theoretical novel biomimetic molecule containing different multiple catalytic peptides. Although single peptides are far less catalytically efficient than protein enzymes, Octopus-arms-mimicking biomolecules containing eight different peptides (Octopuzymes) can efficiently catalyze organic reactions. Since structural information for extant protein enzymes, predicted enzymes based on genome data, and artificially designed enzymes is available for designing Octopuzymes, they could in theory mimic all protein enzyme reactions on our planet. Moreover, besides L-amino acids, peptides can contain D-amino acids, non-natural amino acids, chemically modified amino acids, nucleotides, vitamins, and manmade catalysts, leading to a huge expansion of catalytic space compared with extant protein enzymes. Once a reaction catalyzed by an Octopuzyme is defined, it could be rapidly evolvable via multiple amino acid substitutions on the eight peptides of Octopuzymes.

Asunto(s)

Péptidos , Péptidos/química , Catálisis , Aminoácidos/química , Materiales Biomiméticos/química , Materiales Biomiméticos/metabolismo

RESUMEN

In the field of nuclear toxicology, the knowledge of the interaction of actinides (An) with biomolecules is of prime concern in order to elucidate their toxicity mechanism and to further develop selective decorporating agents. In this work, we demonstrated the great potential of hydrophilic interaction liquid chromatography (HILIC) to separate polar thorium (Th) biomimetic peptide complexes, as a key starting point to tackle these challenges. Th4+ was used as plutonium (Pu4+) analogue and pS16 and pS1368 as synthetic di- and tetra-phosphorylated peptides capable of mimicking the interaction sites of these An in osteopontin (OPN), a hyperphosphorylated protein. The objective was to determine the relative affinity of pS16 and pS1368 towards Th4+, and to evaluate the pS1368 selectivity when Th4+ was in competition complexation reaction with UO22+ at physiological pH. To meet these aims, HILIC was simultaneously coupled to electrospray ionization mass spectrometry (ESI-MS) and inductively coupled plasma mass spectrometry (ICP-MS), which allowed to identify online the molecular structure of the separated complexes and quantify them, in a single step. Dedicated HILIC conditions were firstly set up to separate the new dimeric Th2(peptide)2 complexes with good separation resolution (peptide = pS16 or pS1368). By adding pS16 and pS1368 in different proportions relatively to Th4+, we found that lower or equal proportions of pS16 with respect to pS1368 were not sufficient to displace pS1368 from Th2pS13682 and pS16 proportion higher than pS1368 led to the formation of a predominant ternary complex Th2(pS16)(pS1368), demonstrating preferential Th4+ binding to the tetra-phosphorylated peptide. Finally, online identification and quantification of the formed complexes when Th4+ and UO22+ were mixed in equimolar ratio relatively to pS1368 showed that in spite of pS1368 has been specifically designed to coordinate UO22+, pS1368 is also Th4+-selective and exhibits stronger affinity for this latter than for UO22+. Hence, the results gathered through this approach highlight the impact of Th4+ coordination chemistry on its interaction with pS1368 and more widely to its affinity for biomolecules.

Asunto(s)

Interacciones Hidrofóbicas e Hidrofílicas , Péptidos , Torio , Torio/química , Cromatografía Liquida/métodos , Fosforilación , Péptidos/química , Espectrometría de Masa por Ionización de Electrospray/métodos , Osteopontina/química , Osteopontina/metabolismo , Compuestos de Uranio/química , Materiales Biomiméticos/química , Plutonio/química

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

The glycocalyx, a complex carbohydrate layer on cell surfaces, plays a crucial role in various biological processes. Understanding native glycocalyces' complexity is challenging due to their intricate and dynamic nature. Simplified mimics of native glycocalyces offer insights into glycocalyx functions but often lack molecular precision and fail to replicate key features of the natural analogues like molecular crowding and heteromultivalency. We introduce membrane-anchoring precision glycomacromolecules synthesized via solid-phase polymer synthesis (SPPoS) and thiol-induced, light-activated controlled radical polymerization (TIRP), enabling the construction of crowded and heteromultivalent glycocalyx mimetics with varying molecular weights and densities in giant unilamellar vesicles (GUVs). The incorporation and dynamics of glycomacromolecules in the GUVs are examined via microscopy and fluorescence correlation spectroscopy (FCS) and studies on lectin-carbohydrate-mediated adhesion of GUVs reveal inhibitory and promotional adhesion effects corresponding to different glycocalyx mimetic compositions, bridging the gap between synthetic models and native analogues.

Asunto(s)

Glicocálix , Glicocálix/química , Glicocálix/metabolismo , Liposomas Unilamelares/química , Materiales Biomiméticos/química , Polimerizacion , Polímeros/química

RESUMEN

Climate change and environmental pollution have underscored the urgency for more sustainable alternatives in synthetic polymer production. Nature's repertoire of biopolymers with excellent multifaceted properties alongside biodegradability could inspire next-generation innovative green polymer fabrication routes. Stimuli-induced processing, driven by changes in environmental factors, such as pH, ionic strength, and mechanical forces, plays a crucial role in natural polymeric self-assembly process. This perspective aims to close the gap in understanding biopolymer formation by highlighting the essential role of stimuli triggers in facilitating the bottom-up fabrication, allowing for the formation of intricate hierarchical structures. In particular, this perspective will delve into the stimuli-responsive processing of high-performance biopolymers produced by mussels, caddisflies, velvet worms, sharks, whelks, and squids, which are known for their robust mechanical properties, durability, and wet adhesion capabilities. Finally, we provide an overview of current advancements and challenges in understanding stimuli-induced natural formation pathways and their translation to biomimetic materials.

Asunto(s)

Materiales Biomiméticos , Animales , Biopolímeros/química , Materiales Biomiméticos/química , Concentración de Iones de Hidrógeno , Bivalvos/química

RESUMEN

Biomolecular condensates are dynamic liquid droplets through intracellular liquid-liquid phase separation that function as membraneless organelles, which are highly involved in various complex cellular processes and functions. Artificial analogs formed via similar pathways that can be integrated with biological complexity and advanced functions have received tremendous research interest in the field of synthetic biology. The coacervate droplet-based compartments can partition and concentrate a wide range of solutes, which are regarded as attractive candidates for mimicking phase-separation behaviors and biophysical features of biomolecular condensates. The use of peptide-based materials as phase-separating components has advantages such as the diversity of amino acid residues and customized sequence design, which allows for programming their phase-separation behaviors and the physicochemical properties of the resulting compartments. In this Perspective, we highlight the recent advancements in the design and construction of biomimicry condensates from synthetic peptides relevant to intracellular phase-separating protein, with specific reference to their molecular design, self-assembly via phase separation, and biorelated applications, to envisage the use of peptide-based droplets as emerging biomedical delivery vehicles.

Asunto(s)

Condensados Biomoleculares , Péptidos , Péptidos/química , Condensados Biomoleculares/química , Humanos , Materiales Biomiméticos/química , Biomimética/métodos , Sistemas de Liberación de Medicamentos/métodos , Separación de Fases

RESUMEN

Although the past decade has witnessed a rapid development of oxidoreductase-mimicking nanozymes, the mimicry of cofactors that play key roles in mediating electron and proton transfer remains limited. This study explores how surface Au-H species conjugated to Au nanoparticles (NPs) that imitate formate dehydrogenase (FDH) can serve as cofactors, analogous to NADH in natural enzymes, offering diverse possibilities for FDH-mimicking Au nanozymes to mimic various enzymes. Once O2 is present, Au-H species assist Au NPs to complete the on-demand H2O2 generation for cascade reactions. Alternatively, when oxidizing organic molecules are introduced as substrates, Au-H species confer nitro reductase- and aldehyde reductase-like activities on Au NPs under anaerobic conditions. Furthermore, similar to the dehydrogenase-NADH complex, Au NPs possessing Au-H species are gifted with esterase-like activity for ester hydrolysis. By revealing that Au-H species are prosthetic groups for FDH-mimicking Au nanozymes, this work may inspire explorations into future self-generated cofactor mimics for nanozymes, thereby circumventing the need for exogenous cofactors.

Asunto(s)

Formiato Deshidrogenasas , Oro , Nanopartículas del Metal , Oro/química , Formiato Deshidrogenasas/metabolismo , Formiato Deshidrogenasas/química , Nanopartículas del Metal/química , Propiedades de Superficie , Hidrógeno/química , Hidrógeno/metabolismo , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/metabolismo , Materiales Biomiméticos/química , Materiales Biomiméticos/metabolismo , Oxidación-Reducción

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

Biomimetic artificial olfactory cilia have demonstrated potential in identifying specific volatile organic compounds linked to various diseases, including certain cancers, metabolic disorders, and respiratory conditions. These sensors may facilitate non-invasive disease diagnosis and monitoring. Cilia Motility is the coordinated movement of cilia, which are hair-like projections present on the surface of particular cells in different species. Cilia serve an important part in several biological functions, including motility, fluid movement, and sensory reception. Cilia motility is a complicated process that requires the coordinated interaction of structural components and molecular pathways. Cilia are made up of a highly structured structure known as the axoneme, which is made up of microtubules grouped in a unique pattern. The axoneme is made up of nine outer doublet microtubules and a core pair of singlet microtubules. This arrangement offers structural support and serves as a scaffold for the proteins involved in ciliary movement. Our latest endeavors investigate these Multiphysics phenomena in ciliary beating flows that are inspired by biology, utilizing copper, gold, and titania nanoparticles. We examine their functions in biological systems such as peristaltic transport computationally. Our models give precise two- and three-dimensional velocity, temperature, and concentration solutions by integrating transverse magnetohydrodynamics with laser heating. Furthermore, at the channel wall expressions, the skin friction coefficient, Sherwood number, Nusselt number and optimization of entropy generation are acquired and analyzed. Important properties of the velocity and scalar profiles are revealed by a thorough analysis of dimensionless parameters. The simplified examination provides more insight into the trapping patterns that result from the complex interaction between nanofluid rheology and optics. These findings greatly contribute to our knowledge and improvement of nanofluidic transport technologies in a variety of fields supporting industry, sustainability, and medicine. Our combined computational and experimental methodology clarifies the complex dynamics in these systems and provides design guidance for the engineering of improved fluidic devices that make use of multifunctional nanomaterial interfaces and peristaltic motion.

Asunto(s)

Cilios , Cilios/metabolismo , Cilios/fisiología , Entropía , Materiales Biomiméticos/química , Electroósmosis , Cobre/química , Biomimética/métodos , Oro/química , Titanio/química

RESUMEN

Cardiovascular diseases (CVDs) are one of the leading causes of death worldwide. Despite significant advances in current drug therapies, issues such as poor drug targeting and severe side effects persist. In recent years, nanomedicine has been extensively applied in the research and treatment of CVDs. Among these, biomembrane-modified biomimetic nanodrug delivery systems (BNDSs) have emerged as a research focus due to their unique biocompatibility and efficient drug delivery capabilities. By modifying with biological membranes, BNDSs can effectively reduce recognition and clearance by the immune system, enhance biocompatibility and circulation time in vivo, and improve drug targeting. This review first provides an overview of the classification and pathological mechanisms of CVDs, then systematically summarizes the research progress of BNDSs in the treatment of CVDs, discussing their design principles, functional characteristics, and clinical application potential. Finally, it highlights the issues and challenges faced in the clinical translation of BNDSs.

Asunto(s)

Enfermedades Cardiovasculares , Sistemas de Liberación de Medicamentos , Humanos , Enfermedades Cardiovasculares/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Materiales Biomiméticos/química , Materiales Biomiméticos/uso terapéutico , Biomimética/métodos , Animales , Nanomedicina/métodos , Nanopartículas/química , Sistema de Administración de Fármacos con Nanopartículas/química