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1.
Biomaterials ; 312: 122755, 2025 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-39151270

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
2.
Biomaterials ; 313: 122804, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39236631

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
3.
Biomaterials ; 313: 122796, 2025 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-39226654

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
4.
J Texture Stud ; 55(5): e12864, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39233393

RESUMEN

A masticatory simulator is a mechanical device that mimics the physiological structures of the human oral cavity, chewing movement system, and functions. The advantage of this device lies in real-time tracking and analysis of food boluses within a sealed oral space, offering a direct validation platform for food experiments without constraints related to time, space, and individual variations. The degree to which the masticatory simulator simulates physiological structures reflects its efficacy in replicating oral physiological processes. This review mainly discusses the physiological structures of the oral cavity, the simulation of biomimetic components, and the development, feasibility assessment, applications, and prospects of masticatory simulators in food. The highlight of this review is the analogy of biomimetic component designs in masticatory simulators over the past 15 years. It summarizes the limitations of masticatory simulators and their biomimetic components, proposing potential directions for future development. The purpose of this review is to assist readers in understanding the research progress and latest literature findings on masticatory simulators while also offering insights into the design and innovation of masticatory simulators.


Asunto(s)
Masticación , Boca , Masticación/fisiología , Humanos , Boca/fisiología , Alimentos , Biomimética/métodos
5.
Food Res Int ; 195: 114898, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39277214

RESUMEN

The main objective of this study was to assess the ability of the NEar Real Digestive Tract (NERDT), a computer-controlled biomimetic in vitro digestion system that considers the biomechanics of the stomach, to reproduce physiologically relevant features of skimmed milk gastric digestion. A second objective was to evaluate the influence of pepsin on the gastric coagulation and emptying of milk proteins from experiments performed with and without pepsin. A mass balance model over the stomach, assuming a perfectly stirred reactor behaviour, has been developed. The results show that the NERDT can adequately reproduce the targeted kinetics of gastric acidification and emptying, with a sieving effect that naturally leads to a delayed emptying of caseins. Milk coagulated earlier and more chyme was emptied towards the end of the experiments in the presence of pepsin than without, hence illustrating the key influence of pepsin on the gastric coagulation of caseins and subsequent hydrolysis and emptying of dairy particles. Overall, this study shows that the NERDT can be adequately controlled to achieve desired gastric digestion conditions, and appears to be a very useful tool to further improve the knowledge of the gastric digestion behaviour of complex foods such as milk.


Asunto(s)
Biomimética , Digestión , Leche , Pepsina A , Digestión/fisiología , Animales , Pepsina A/metabolismo , Humanos , Leche/química , Biomimética/métodos , Modelos Biológicos , Concentración de Iones de Hidrógeno , Vaciamiento Gástrico/fisiología , Caseínas/metabolismo , Estómago/fisiología , Cinética , Proteínas de la Leche/metabolismo
6.
J Nanobiotechnology ; 22(1): 545, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39238009

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
7.
Biomacromolecules ; 25(9): 5468-5488, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39178343

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
8.
Bioinspir Biomim ; 19(5)2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39163889

RESUMEN

Autonomous ocean-exploring vehicles have begun to take advantage of onboard sensor measurements of water properties such as salinity and temperature to locate oceanic features in real time. Such targeted sampling strategies enable more rapid study of ocean environments by actively steering towards areas of high scientific value. Inspired by the ability of aquatic animals to navigate via flow sensing, this work investigates hydrodynamic cues for accomplishing targeted sampling using a palm-sized robotic swimmer. As proof-of-concept analogy for tracking hydrothermal vent plumes in the ocean, the robot is tasked with locating the center of turbulent jet flows in a 13,000-liter water tank using data from onboard pressure sensors. To learn a navigation strategy, we first implemented RL on a simulated version of the robot navigating in proximity to turbulent jets. After training, the RL algorithm discovered an effective strategy for locating the jets by following transverse velocity gradients sensed by pressure sensors located on opposite sides of the robot. When implemented on the physical robot, this gradient following strategy enabled the robot to successfully locate the turbulent plumes at more than twice the rate of random searching. Additionally, we found that navigation performance improved as the distance between the pressure sensors increased, which can inform the design of distributed flow sensors in ocean robots. Our results demonstrate the effectiveness and limits of flow-based navigation for autonomously locating hydrodynamic features of interest.


Asunto(s)
Biomimética , Peces , Hidrodinámica , Océanos y Mares , Robótica , Natación , Robótica/instrumentación , Animales , Peces/fisiología , Biomimética/métodos , Biomimética/instrumentación , Natación/fisiología , Movimientos del Agua , Algoritmos , Diseño de Equipo , Simulación por Computador
9.
Nanotechnology ; 35(47)2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39173646

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
10.
Biomolecules ; 14(8)2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39199348

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
11.
Int J Biol Macromol ; 277(Pt 3): 134485, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39102926

RESUMEN

The blood glucose concentration in aquatic organisms, a crucial indicator reflecting their health status, holds significant importance for detecting glucose levels in serum in terms of processing and quality monitoring. In this study, a novel POD biomimetic enzyme (p-BEs) with horseradish peroxidase catalytic properties was designed, optimized, and its mechanism was discussed in detail. Based on this, a portable system has been developed capable of determining glucose levels in three ways: quantitatively analyzed through UV-Vis/MD, quantitatively analyzed on-site using a mobile phone RGB, and semi-quantitatively analyzed through a drip plate. Meanwhile, compared with other catalytic methods for detecting glucose, we achieved a lower limit of detection (0.03 µM) and shorter detection time (12 min), with high catalytic activity. This study provides new insights into the design of efficient and reliable cascade catalytic systems responsive to glucose, offering a low-cost, simplicity of operation method for glucose detection.


Asunto(s)
Técnicas Biosensibles , Peroxidasa de Rábano Silvestre , Técnicas Biosensibles/métodos , Peroxidasa de Rábano Silvestre/química , Peroxidasa de Rábano Silvestre/metabolismo , Glucosa/análisis , Glucemia/análisis , Catálisis , Materiales Biomiméticos/química , Límite de Detección , Biomimética/métodos , Biocatálisis
12.
Biosens Bioelectron ; 264: 116639, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39121617

RESUMEN

Tumor-derived extracellular vesicles detection has emerged as an important clinical liquid biopsy approach for cancer diagnosis. In this work, we developed a novel hybrid plasmonic nanocavity consisting of hexagonal Au nanoplates nanoarray, SnS2/Au nanosheet layer and biomimetic lipid bilayer. Firstly, the hybrid plasmonic nanocavity combined the optical confinement for the ECL regulation and the biological recognition for the detection of extracellular vesicles. Secondly, MXene-derived Ti2N QDs have been prepared as ECL nanoprobe to label extracellular vesicles. Moreover, biomimetic lipid bilayer with specific aptamer was used to identify extracellular vesicles and integrate Ti2N QDs into the nanocavity with membrane fusion strategy. Due to the significant electromagnetic field enhancement at the cavity region, the hybrid plasmonic nanocavity provided strong field confinement to concentrate and redistribute the ECL emission of QDs with a 9.3-fold enhancement. The hybrid plasmonic nanocavity-based ECL sensing system improved the spatial controllability of EVs analysis and the accurate resolution of specific protein. It achieved the sensitive detection of extracellular vesicles in ascites and successfully distinguished the peritoneal metastasis of gastric cancer.


Asunto(s)
Técnicas Biosensibles , Vesículas Extracelulares , Oro , Vesículas Extracelulares/química , Humanos , Técnicas Biosensibles/métodos , Oro/química , Materiales Biomiméticos/química , Puntos Cuánticos/química , Biomimética/métodos , Neoplasias Gástricas/patología , Membrana Dobles de Lípidos/química
13.
Bioinspir Biomim ; 19(5)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39146962

RESUMEN

In this paper, the innovative design of a robotic hand with soft jointed structure is carried out and a tendon-driven mechanism, a master-slave motor coordinated drive mechanism, a thumb coupling transmission mechanism and a thumb steering mechanism are proposed. These innovative designs allow for more effective actuation in each finger, enhancing the load capacity of the robotic hand while maintaining key performance indicators such as dexterity and adaptability. A mechanical model of the robotic finger was made to determine the application limitations and load capacity. The robotic hand was then prototyped for a set of experiments. The experimental results showed that the proposed theoretical model were reliable. Also, the fingertip force of the robotic finger could reach up to 10.3 N, and the load force could reach up to 72.8 N. When grasping target objects of different sizes and shapes, the robotic hand was able to perform the various power grasping and precision grasping in the Cutkosky taxonomy. Moreover, the robotic hand had good flexibility and adaptability by means of adjusting the envelope state autonomously.


Asunto(s)
Diseño de Equipo , Fuerza de la Mano , Mano , Robótica , Robótica/instrumentación , Mano/fisiología , Humanos , Fuerza de la Mano/fisiología , Dedos/fisiología , Biomimética/métodos , Tendones/fisiología , Modelos Biológicos
14.
Bioinspir Biomim ; 19(5)2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39151462

RESUMEN

In order to adapt to complex and changing environments, animals have a wide variety of locomotor forms, which has inspired the investigation of their deformation and driving mechanisms. In this paper, we propose a computational design method for muscle-driven soft robots to satisfy desired deformations, aiming to mimic the deformation behavior of muscle-driven animals in nature. In this paper, we generate the ideal muscle-driven layout for the soft robot by inputting an initial shape and a desired shape, so that it can closely achieve the desired deformation. The material point method is utilized to simulate the soft medium so as to achieve the effect of coupling and coordinated deformation of arbitrary shapes. Our method efficiently searches for muscle layouts corresponding to various deformations and realizes the deformation behaviors of a variety of bio-inspired robots, including soft robots such as bionic snakes, frogs, and human faces. Experimental results show that for both the bionic snake and frog soft robots, the overlap of the geometric contour regions between the actual and simulated deformations is more than 90%, which validates the effectiveness of the method. In addition, the global muscle distributions of the bionic snake and human face soft robots during motion are generated and validated by effective simulation.


Asunto(s)
Biomimética , Simulación por Computador , Diseño de Equipo , Robótica , Robótica/instrumentación , Animales , Biomimética/métodos , Humanos , Músculo Esquelético/fisiología , Modelos Biológicos , Anuros/fisiología , Locomoción/fisiología
15.
Theranostics ; 14(11): 4375-4392, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39113803

RESUMEN

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


Asunto(s)
Trastorno del Espectro Autista , Autofagia , Barrera Hematoencefálica , Nanopartículas , Estrés Oxidativo , Sirolimus , Sirolimus/administración & dosificación , Sirolimus/farmacología , Estrés Oxidativo/efectos de los fármacos , Trastorno del Espectro Autista/tratamiento farmacológico , Trastorno del Espectro Autista/metabolismo , Animales , Autofagia/efectos de los fármacos , Nanopartículas/química , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Ratones , Humanos , Sistemas de Liberación de Medicamentos/métodos , Modelos Animales de Enfermedad , Masculino , Materiales Biomiméticos/administración & dosificación , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Biomimética/métodos , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Péptidos/administración & dosificación , Especies Reactivas de Oxígeno/metabolismo , Ácido Valproico/administración & dosificación , Ácido Valproico/farmacología
16.
Phys Rev Lett ; 133(4): 048302, 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39121428

RESUMEN

Direct mechanical coupling is known to be critical for establishing synchronization among cilia. However, the actual role of the connections is still elusive-partly because controlled experiments in living samples are challenging. Here, we employ an artificial ciliary system to address this issue. Two cilia are formed by chains of self-propelling robots and anchored to a shared base so that they are purely mechanically coupled. The system mimics biological ciliary beating but allows fine control over the beating dynamics. With different schemes of mechanical coupling, artificial cilia exhibit rich motility patterns. Particularly, their synchronous beating display two distinct modes-analogous to those observed in C. reinhardtii, the biciliated model organism for studying synchronization. Close examination suggests that the system evolves towards the most dissipative mode. Using this guideline in both simulations and experiments, we are able to direct the system into a desired state by altering the modes' respective dissipation. Our results have significant implications in understanding the synchronization of cilia.


Asunto(s)
Biomimética , Cilios , Robótica , Cilios/fisiología , Biomimética/métodos , Modelos Biológicos , Chlamydomonas reinhardtii/fisiología
17.
Int J Mol Sci ; 25(15)2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39126107

RESUMEN

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


Asunto(s)
Materiales Biomiméticos , Membrana Celular , Accidente Cerebrovascular Isquémico , Nanopartículas , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/patología , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Nanopartículas/química , Animales , Membrana Celular/metabolismo , Biomimética/métodos , Sistemas de Liberación de Medicamentos , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo
18.
Mol Pharm ; 21(9): 4664-4672, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39133897

RESUMEN

The blood-brain barrier (BBB) poses a significant challenge for drug delivery and is linked to various neurovascular disorders. In vitro BBB models provide a tool to investigate drug permeation across the BBB and the barrier's response to external injury events. Yet, existing models lack fidelity in replicating the BBB's complexity, hindering a comprehensive understanding of its functions. This study introduces a three-dimensional (3D) model using polyethylene glycol (PEG) hydrogels modified with biomimetic peptides that represent recognition sequences of key proteins in the brain. Hydrogels were functionalized with recognition sequences for laminin (IKVAV) and fibronectin peptides (RGD) and chemically cross-linked with matrix metalloprotease-sensitive peptides (MMPs) to mimic the extracellular matrix of the BBB. Astrocytes and endothelial cells were seeded within and on the surface of the hydrogels, respectively. The barrier integrity was assessed through different tests including transendothelial electrical resistance (TEER), the permeability of sodium fluorescence (Na-F), the permeability of Evan's blue bound to albumin (EBA), and the expression of zonula occluden-1 (ZO-1) in seeded endothelial cells. Hydrogels with a combination of RGD and IKVAV peptides displayed superior performance, exhibiting significantly higher TEER values (55.33 ± 1.47 Ω·cm2) at day 5 compared to other 2D controls including HAECs-monoculture and HAECs-cocultured with NHAs seeded on well inserts and 3D controls including RGD hydrogel and RGD-IKVAV monoculture with HAECs and RGD hydrogel cocultured with HAECs and NHAs. The designed 3D system resulted in the lowest Evan's blue permeability at 120 min (0.215 ± 0.055 µg/mL) compared to controls. ZO-1 expression was significantly higher and formed a relatively larger network in the functionalized hydrogel cocultured with astrocytes and endothelial cells compared to the controls. Thus, the designed 3D model effectively recapitulates the main BBB structure and function in vitro and is expected to contribute to a deeper understanding of pathological CNS angiogenesis and the development of effective CNS medications.


Asunto(s)
Astrocitos , Barrera Hematoencefálica , Técnicas de Cocultivo , Células Endoteliales , Hidrogeles , Péptidos , Polietilenglicoles , Barrera Hematoencefálica/metabolismo , Astrocitos/metabolismo , Polietilenglicoles/química , Células Endoteliales/metabolismo , Técnicas de Cocultivo/métodos , Hidrogeles/química , Péptidos/química , Humanos , Oligopéptidos/química , Fibronectinas/química , Fibronectinas/metabolismo , Laminina/química , Animales , Biomimética/métodos , Materiales Biomiméticos/química , Células Cultivadas
19.
Int J Biol Macromol ; 277(Pt 4): 134529, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39111485

RESUMEN

Living organisms have developed a miraculous biomineralization strategy to form multistage organic-inorganic composites through the orderly assembly of hard/soft substances, achieving mechanical enhancement of materials from the nanoscale to the macroscale. Inspired by biominerals, this study used polydopamine (PDA) coating as a template to induce the growth of hydroxyapatite (HAP) on the surface of carbon fibers (CFs) for enhancing the interfacial properties of the CF/epoxy resin composites. This polydopamine-assisted hydroxyapatite formation (pHAF) biomimetic mineralization strategy constructs soft/hard ordered structure on the CF surface, which not only improves the chemical reaction activity of the CFs but also increases the fiber surface roughness. This, in turn, enhances the interaction and loading delivery among the fibers and the matrix. Compared to the untreated carbon fiber/epoxy resin (CF/EP) composites, the prepared composites showed a substantial enhancement in interlaminar shear strength (ILSS), flexural strength, and interfacial shear strength (IFSS), with improvements of 45.2 %, 46.9 %, and 60.5 %, respectively. This can be attributed to the HAP nanolayers increasing the adhesion and mechanical interlocking with the CFs to the matrix. This study provides an interface modification method of biomimetic mineralization for the preparation of high strength CF composites.


Asunto(s)
Fibra de Carbono , Durapatita , Indoles , Polímeros , Indoles/química , Durapatita/química , Polímeros/química , Fibra de Carbono/química , Materiales Biomiméticos/química , Biomimética/métodos , Fenómenos Mecánicos , Resistencia al Corte , Propiedades de Superficie , Resinas Epoxi/química
20.
Proc Natl Acad Sci U S A ; 121(33): e2407971121, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39110725

RESUMEN

Artificial neuromorphic devices can emulate dendric integration, axonal parallel transmission, along with superior energy efficiency in facilitating efficient information processing, offering enormous potential for wearable electronics. However, integrating such circuits into textiles to achieve biomimetic information perception, processing, and control motion feedback remains a formidable challenge. Here, we engineer a quasi-solid-state iontronic synapse fiber (ISF) comprising photoresponsive TiO2, ion storage Co-MoS2, and an ion transport layer. The resulting ISF achieves inherent short-term synaptic plasticity, femtojoule-range energy consumption, and the ability to transduce chemical/optical signals. Multiple ISFs are interwoven into a synthetic neural fabric, allowing the simultaneous propagation of distinct optical signals for transmitting parallel information. Importantly, IFSs with multiple input electrodes exhibit spatiotemporal information integration. As a proof of concept, a textile-based multiplexing neuromorphic sensorimotor system is constructed to connect synaptic fibers with artificial fiber muscles, enabling preneuronal sensing information integration, parallel transmission, and postneuronal information output to control the coordinated motor of fiber muscles. The proposed fiber system holds enormous promise in wearable electronics, soft robotics, and biomedical engineering.


Asunto(s)
Sinapsis , Textiles , Sinapsis/fisiología , Dispositivos Electrónicos Vestibles , Biomimética/métodos , Biomimética/instrumentación , Humanos , Plasticidad Neuronal/fisiología
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