Biomimetic nanoplatform with microbiome modulation and antioxidant functions ameliorating insulin resistance and pancreatic ß-cell dysfunction for T2DM management.

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.

Tailored extracellular matrix-mimetic coating facilitates reendothelialization and tissue healing of cardiac occluders.

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.

Genetically engineered CD276-anchoring biomimetic nanovesicles target senescent escaped tumor cells to overcome chemoresistant and immunosuppressive breast cancer.

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.

MSCs biomimetic ultrasonic phase change nanoparticles promotes cardiac functional recovery after acute myocardial infarction.

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.

In-situ activation of biomimetic single-site bioorthogonal nanozyme for tumor-specific combination therapy.

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.

Encoding spatiotemporal asymmetry in artificial cilia with a ctenophore-inspired soft-robotic platform.

A remarkable variety of organisms use metachronal coordination (i.e. numerous neighboring appendages beating sequentially with a fixed phase lag) to swim or pump fluid. This coordination strategy is used by microorganisms to break symmetry at small scales where viscous effects dominate and flow is time-reversible. Some larger organisms use this swimming strategy at intermediate scales, where viscosity and inertia both play important roles. However, the role of individual propulsor kinematics-especially across hydrodynamic scales-is not well-understood, though the details of propulsor motion can be crucial for the efficient generation of flow. To investigate this behavior, we developed a new soft robotic platform using magnetoactive silicone elastomers to mimic the metachronally coordinated propulsors found in swimming organisms. Furthermore, we present a method to passively encode spatially asymmetric beating patterns in our artificial propulsors. We investigated the kinematics and hydrodynamics of three propulsor types, with varying degrees of asymmetry, using Particle Image Velocimetry and high-speed videography. We find that asymmetric beating patterns can move considerably more fluid relative to symmetric beating at the same frequency and phase lag, and that asymmetry can be passively encoded into propulsors via the interplay between elastic and magnetic torques. Our results demonstrate that nuanced differences in propulsor kinematics can substantially impact fluid pumping performance. Our soft robotic platform also provides an avenue to explore metachronal coordination at the meso-scale, which in turn can inform the design of future bioinspired pumping devices and swimming robots.

Synthesis of a Zn(II)-2-aminoimidazole Framework as an Efficient Carbonic Anhydrase Mimic.

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.

Biomimetic Peptide Nanonets: Exploiting Bacterial Entrapment and Macrophage Rerousing for Combatting Infections.

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.

Biomimetic Lipid Raft: Domain Stability and Interaction with Physiologically Active Molecules.

The cell membrane, also called the plasma membrane, is the membrane on the cytoplasmic surface that separates the extracellular from the intracellular. It is thin, about 10 nm thick when viewed with an electron microscope, and is composed of two monolayers of phospholipid membranes (lipid bilayers) containing many types of proteins. It is now known that this cell membrane not only separates the extracellular from the intracellular, but is also involved in sensory stimuli such as pain, itching, sedation, and excitement. Since the "Fluid mosaic model" was proposed for cell membranes, molecules have been thought to be homogeneously distributed on the membrane surface. Later, at the end of the twentieth century, the existence of "Phase-separated microdomain structures" consisting of ordered phases rich in saturated lipids and cholesterol was suggested, and these were termed "Lipid rafts." A model in which lipid rafts regulate cell signaling has been proposed and is the subject of active research.This chapter first outlines the physicochemical properties and thermodynamic models of membrane phase separation (lipid rafts), which play an important role in cell signaling. Next, how physiologically active molecules such as local anesthetics, cooling agents (menthol), and warming agents (capsaicin) interact with artificial cell membranes will be presented.It is undeniable that the plasma membrane contains many channels and receptors that are involved in the propagation of sensory stimuli. At the same time, however, it is important to understand that the membrane exerts a significant influence on the intensity and propagation of these stimuli.

Biomimetic Iron-Based Nanoparticles Remodel Immunosuppressive Tumor Microenvironment for Metabolic Immunotherapy.

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.

Macrophage membrane-camouflaged biomimetic nanoparticles for rheumatoid arthritis treatment via modulating macrophage polarization.

Rheumatoid arthritis (RA) is a debilitating autoimmune disease characterized by chronic joint inflammation and cartilage damage. Current therapeutic strategies often result in side effects, necessitating the development of targeted and safer treatment options. This study introduces a novel nanotherapeutic system, 2-APB@DGP-MM, which utilizes macrophage membrane (MM)-encapsulated nanoparticles (NPs) for the targeted delivery of 2-Aminoethyl diphenylborinate (2-APB) to inflamed joints more effectively. The NPs are designed with a matrix metalloproteinase (MMP)-cleavable peptide, allowing for MMP-responsive drug release within RA microenvironment. Comprehensive in vitro and in vivo assays confirmed the successful synthesis and loading of 2-APB into the DSPE-GPLGVRGC-PEG (DGP) NPs, as well as their ability to repolarize macrophages from a pro-inflammatory M1 to an anti-inflammatory M2 phenotype. The NPs demonstrated high biocompatibility, low cytotoxicity, and enhanced cellular uptake. In a collagen-induced arthritis (CIA) mouse model, intra-articular injection of 2-APB@DGP-MM significantly reduced synovial inflammation and cartilage destruction. Histological analysis corroborated these findings, demonstrating marked improvements in joint structure and delayed disease progression. Above all, the 2-APB@DGP-MM nanotherapeutic system offers a promising and safe approach for RA treatment by modulating macrophage polarization and delivering effective agents to inflamed joints.

Theoretical Framework for Novel Catalytic Biomolecules Composed of Multiple Peptides.

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.

Construction of a thermoresponsive molecularly imprinted biomimetic hydrogel-based virus sensor and non-invasive cyclable detection of EV71.

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.

Orally biomimetic metal-phenolic nanozyme with quadruple safeguards for intestinal homeostasis to ameliorate ulcerative colitis.

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.

Hydrophilic interaction liquid chromatography: An efficient tool for assessing thorium interaction with phosphorylated biomimetic peptides.

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.

Bioinspired synergy strategy based on the integration of nanozyme into a molecularly imprinted polymer for improved enzyme catalytic mimicry and selective biosensing.

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.

Novel biomimetic hybrid plasmonic nanocavity-based ECL strategy for the detection of extracellular vesicles.

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.

Homologous Tumor Cell-Derived Biomimetic Nano-Trojan Horse Integrating Chemotherapy with Genetherapy for Boosting Triple-Negative Breast Cancer Therapy.

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

Bioinspired Flexible Kevlar/Hydrogel Composites with Antipuncture and Strain-Sensing Properties for Personal Protective Equipment.

Currently, multifunction has become an essential direction of personal protective equipment (PPE), but achieving the protective effect, flexibility, physiological comfort, and intelligent application of PPE simultaneously is still a challenge. Herein, inspired by the meso-structure of rhinoceros skin, a novel strategy is proposed by compounding an ammonium sulfate ((NH4)2SO4) solution soaked gelatin hydrogel with the high weight fraction and vertically interwoven Kevlar fibers to manufacture a flexible and wearable composite with enhanced puncture resistance and strain-sensing properties. After (NH4)2SO4 solution immersion, the hydrogel's tensile strength, toughness, and fracture strain were up to 3.77 MPa, 4.26 MJ/m3, and 305.19%, respectively, indicating superior mechanical properties. The Kevlar/hydrogel composites revealed excellent puncture resistance (quasi-static of 132.06 N and dynamic of 295.05 N), flexibility (138.13 mN/cm), and air and moisture permeability (17.83 mm/s and 2092.73 g m-2 day-1), demonstrating a favorable balance between the protective effect and wearing comfort even after 7 days of environmental exposure. Meanwhile, salt solution immersion endowed the composite with excellent strain-sensing properties at various bending angles (30-90°) and frequencies (0.25-1 Hz) and allowed it to monitor different human motions directly in real-time. The rhinoceros-skin-inspired Kevlar/hydrogel composites provide a simple and economical solution for antipuncture materials that combine high protective effects, a comfortable wearing experience, and good strain-sensing properties, promising multifunctional PPE in the future.

Application of artificial backbone connectivity in the development of metalloenzyme mimics.

Metal-dependent enzymes are abundant and vital catalytic agents in nature. The functional versatility of metalloenzymes has made them common targets for improvement by protein engineering as well as mimicry by de novo designed sequences. In both strategies, the incorporation of non-canonical cofactors and/or non-canonical side chains has proved a useful tool. Less explored-but similarly powerful-is the utilization of non-canonical covalent modifications to the polypeptide backbone itself. Such efforts can entail either introduction of limited artificial monomers in natural chains to produce heterogeneous backbones or construction of completely abiotic oligomers that adopt defined folds. Herein, we review recent research applying artificial protein-like backbones in the construction of metalloenzyme mimics, highlighting progress as well as open questions in this emerging field.