Nanozymes with biomimetically designed properties for cancer treatment.

Nanozymes, as a type of nanomaterials with enzymatic catalytic activity, have demonstrated tremendous potential in cancer treatment owing to their unique biomedical properties. However, the heterogeneity of tumors and the complex tumor microenvironment pose significant challenges to the in vivo catalytic efficacy of traditional nanozymes. Drawing inspiration from natural enzymes, scientists are now using biomimetic design to build nanozymes from the ground up. This approach aims to replicate the key characteristics of natural enzymes, including active structures, catalytic processes, and the ability to adapt to the tumor environment. This achieves selective optimization of nanozyme catalytic performance and therapeutic effects. This review takes a deep dive into the use of these biomimetically designed nanozymes in cancer treatment. It explores a range of biomimetic design strategies, from structural and process mimicry to advanced functional biomimicry. A significant focus is on tweaking the nanozyme structures to boost their catalytic performance, integrating them into complex enzyme networks similar to those in biological systems, and adjusting functions like altering tumor metabolism, reshaping the tumor environment, and enhancing drug delivery. The review also covers the applications of specially designed nanozymes in pan-cancer treatment, from catalytic therapy to improved traditional methods like chemotherapy, radiotherapy, and sonodynamic therapy, specifically analyzing the anti-tumor mechanisms of different therapeutic combination systems. Through rational design, these biomimetically designed nanozymes not only deepen the understanding of the regulatory mechanisms of nanozyme structure and performance but also adapt profoundly to tumor physiology, optimizing therapeutic effects and paving new pathways for innovative cancer treatment.

Remineralization Potential of a Novel Biomimetic Material (Self-assembling Peptide P11-4) on Early Enamel Caries: An In Vitro Study.

AIM: To assess the remineralizing potential of self-assembling peptide P11-4 and compare it to the remineralizing potential of fluoride varnish using DIAGNOdentTM, as well as the amount of mineral gain after application of fluoride varnish and self-assembling peptide P11-4. MATERIALS AND METHODS: This study included 20 premolars extracted during orthodontic therapy with all surfaces intact and free of hypoplastic regions, white spot lesions (WSL) and dental caries. The teeth sample for Curodont RepairTM (self-assembling P11-4) and Bifluorid 10® (fluoride varnish) was equally divided. On each tooth surface, a 2 × 2 mm window was created. The samples were immersed in a demineralizing solution for 96 hours before being subjected to DIAGNOdentTM pen reading, ICDAS-II scoring, and scanning electron microscopy-energy-dispersive X-ray (SEM-EDX) analysis on one half of the sample. The remineralizing agents were applied to the second half of the sample according to the manufacturer's instructions and placed in artificial saliva for 21 days, with the artificial salvia being replaced every 24 hours. After 21 days, the second half of the sample was subjected to DIAGNOdentTM pen reading, ICDAS-II score, and SEM-EDX analysis. RESULTS: Following remineralization, the DIAGNOdentTM pen and ICDAS-II score values differed statistically between the two groups, with the Bifluorid 10® group reporting higher mean values (p > 0.05) using t-test analysis. Energy-dispersive X-ray analysis using the t-test revealed a statistically significant result for remineralization (p < 0.05), with CurodontTM Repair group (55.150.84) reporting better mean values than Bifluorid 10® for phosphorus and calcium, but Bifluorid 10® reporting a higher result in remineralization (p < 0.05) than CurodontTM Repair for fluoride. CONCLUSION: CurodontTM Repair showed better remineralizing potential compared with Bifluorid 10® varnish. In terms of the mineral gain, CurodontTM Repair showed better results for calcium and phosphorus post-remineralization. Whereas Bifluorid 10® showed a higher gain in terms of fluoride. Self-assembling peptide P11-4 can be used as an alternative to fluoride varnish for remineralizing WSL. CLINICAL SIGNIFICANCE: Self-assembling polypeptide P11-4 is a novel remineralizing agent for initial enamel lesions, which is the least-invasive method of enamel remineralization.

Mussel-Based Biomimetic Strategies in Musculoskeletal Disorder Treatment: From Synthesis Principles to Diverse Applications.

Musculoskeletal disorders are the second leading cause of disability worldwide, posing a huge global burden to the public sanitation system. Currently, tissue engineering-based approaches act as effective strategies, which are, however, challenging in limited application scenarios. Mussel-based biomimetic materials, exhibit numerous unique properties such as intense adhesion, biocompatibility, moisture resistance, and injectability, to name only a few, and have attracted extensive research interest. In particular, featuring state-of-the-art properties, mussel-inspired biomaterials have been widely explored in innumerable musculoskeletal disorder treatments including osteochondral defects, osteosarcoma, osteoarthritis, ligament rupture, and osteoporosis. Nevertheless, a comprehensive and timely discussion of their applications in musculoskeletal disorders is insufficient. In this review, we emphasize on (1) the main categories and characteristics of mussel foot proteins and their fundamental mechanisms for the spectacular adhesion in mussels; (2) the diverse synthetic methods and modification of various polymers; and (3) the emerging applications of mussel-biomimetic materials, the future perspectives, and challenges, especially in the area of musculoskeletal disorder. We envision that this review will provide a unique and insightful perspective to improve the development of a new generation of mussel biomimetic strategies.

Synergistically Enhancing the Therapeutic Effect on Cancer, via Asymmetric Bioinspired Materials.

The undesirable side effects of conventional chemotherapy are one of the major problems associated with cancer treatment. Recently, with the development of novel nanomaterials, tumor-targeted therapies have been invented in order to achieve more specific cancer treatment with reduced unfavorable side effects of chemotherapic agents on human cells. However, the clinical application of nanomedicines has some shortages, such as the reduced ability to cross biological barriers and undesirable side effects in normal cells. In this order, bioinspired materials are developed to minimize the related side effects due to their excellent biocompatibility and higher accumulation therapies. As bioinspired and biomimetic materials are mainly composed of a nanometric functional agent and a biologic component, they can possess both the physicochemical properties of nanomaterials and the advantages of biologic agents, such as prolonged circulation time, enhanced biocompatibility, immune modulation, and specific targeting for cancerous cells. Among the nanomaterials, asymmetric nanomaterials have gained attention as they provide a larger surface area with more active functional sites compared to symmetric nanomaterials. Additionally, the asymmetric nanomaterials are able to function as two or more distinct components due to their asymmetric structure. The mentioned properties result in unique physiochemical properties of asymmetric nanomaterials, which makes them desirable materials for anti-cancer drug delivery systems or cancer bio-imaging systems. In this review, we discuss the use of bioinspired and biomimetic materials in the treatment of cancer, with a special focus on asymmetric nanoparticle anti-cancer agents.

Identification of Potential ACE2-Derived Peptide Mimetics in SARS-CoV-2 Omicron Variant Therapeutics using Computational Approaches.

The COVID-19 pandemic has become a global health challenge because of the emergence of distinct variants. Omicron, a new variant, is recognized as a variant of concern (VOC) by the World Health Organization (WHO) because of its higher mutations and accelerated human infection. The infection rate is strongly dependent on the binding rate of the receptor binding domain (RBD) against human angiotensin converting enzyme-2 (ACE2human) receptor. Inhibition of protein-protein (RBDs(SARS-CoV-2/omicron)-ACE2human) interaction has been already proven to inhibit viral infection. We have systematically designed ACE2human-derived peptides and peptide mimetics that have high binding affinity toward RBDomicron. Our peptide mutational analysis indicated the influence of canonical amino acids on the peptide binding process. Herein, efforts have been made to explore the atomistic details and events of RBDs(SARS-CoV-2/omicron)-ACE2human interactions by using molecular dynamics simulation. Our studies pave a path for developing therapeutic peptidomimetics against omicron.

Organotropic Targeting of Biomimetic Nanoparticles to Treat Lung Disease.

Active targeting strategies aimed at improving drug homing while reducing systemic toxicity are widely being pursued in the growing field of nanomedicine. While they can be effective, these approaches often require the identification of cell-specific targets and in-depth knowledge of receptor binding interactions. More recently, there has been significant interest in biomimetic nanoformulations capable of replicating the properties of naturally occurring systems. In particular, the advent of cell membrane coating nanotechnology has enabled researchers to leverage the inherent tropisms displayed by living cells, bypassing many of the challenges associated with traditional bottom-up nanoengineering. In this work, we report on a biomimetic organotropic nanodelivery system for localizing therapeutic payloads to the lungs. Metastatic breast cancer exosomes, which are lung tropic due to their unique surface marker expression profile, are used to coat nanoparticle cores loaded with the anti-inflammatory drug dexamethasone. In vivo, these nanoparticles demonstrate enhanced accumulation in lung tissue and significantly reduce proinflammatory cytokine burden in a lung inflammation model. Overall, this work highlights the potential of using biomimetic organ-level delivery strategies for the management of certain disease conditions.

A biomimetic ZIF nanoagent for synergistic regulation of glutamine metabolism and intracellular acidosis of cancer.

A homotypic cancer cell membrane camouflaged zeolitic imidazolate framework (ZIF)-based nanoagent with co-loading of two inhibitors was developed, which could suppress the efflux of protons to induce intracellular acidic stress and down-regulate glutamine metabolism to reduce the energy supply. As a compensation, glycometabolism would be upregulated with simultaneous production of large amounts of lactic acid, which could in turn aggravate the acidosis and further realize a synergetic cancer treatment.

pH-Responsive Multifunctional Theranostic Rapamycin-Loaded Nanoparticles for Imaging and Treatment of Acute Ischemic Stroke.

Stroke is the second leading cause of death globally and the most common cause of severe disability. Several barriers need to be addressed more effectively to treat stroke, including efficient delivery of therapeutic agents, rapid release at the infarct site, precise imaging of the infarct site, and drug distribution monitoring. The present study aimed to develop a bio-responsive theranostic nanoplatform with signal-amplifying capability to deliver rapamycin (RAPA) to ischemic brain tissues and visually monitor drug distribution. A pH-sensitive theranostic RAPA-loaded nanoparticle system was designed since ischemic tissues have a low-pH microenvironment compared with normal tissues. The nanoparticles demonstrated good stability and biocompatibility and could efficiently load rapamycin, followed by its rapid release in acidic environments, thereby improving therapeutic accuracy. The nano-drug-delivery system also exhibited acid-enhanced magnetic resonance imaging (MRI) and near-infrared fluorescence (NIRF) imaging signal properties, enabling accurate multimodal imaging with minimal background noise, thus improving drug tracing and diagnostic accuracy. Finally, in vivo experiments confirmed that the nanoparticles preferentially aggregated in the ischemic hemisphere and exerted a neuroprotective effect in rats with transient middle cerebral artery occlusion (tMCAO). These pH-sensitive multifunctional theranostic nanoparticles could serve as a potential nanoplatform for drug tracing as well as the treatment and even diagnosis of acute ischemic stroke. Moreover, they could be a universal solution to achieve accurate in vivo imaging and treatment of other diseases.

Restoring Cardiac Functions after Myocardial Infarction-Ischemia/Reperfusion via an Exosome Anchoring Conductive Hydrogel.

Both myocardial infarction (MI) and the follow-up reperfusion will lead to an inevitable injury to myocardial tissues, such as cardiac dysfunctions, fibrosis, and reduction of intercellular cell-to-cell interactions. Recently, exosomes (Exo) derived from stem cells have demonstrated a robust capability to promote angiogenesis and tissue repair. However, the short half-life of Exo and rapid clearance lead to insufficient therapeutic doses in the lesion area. Herein, an injectable conductive hydrogel is constructed to bind Exo derived from human umbilical cord mesenchymal stem cells to treat myocardial injuries after myocardial infarction-ischemia/reperfusion (MI-I/R). To this end, a hyperbranched epoxy macromer (EHBPE) grafted by an aniline tetramer (AT) was synthesized to cross-link thiolated hyaluronic acid (HA-SH) and thiolated Exo anchoring a CP05 peptide via an epoxy/thiol "click" reaction. The resulting Gel@Exo composite system possesses multiple features, such as controllable gelation kinetics, shear-thinning injectability, conductivity matching the native myocardium, soft and dynamic stability adapting to heartbeats, and excellent cytocompatibility. After being injected into injured hearts of rats, the hydrogel effectively prolongs the retention of Exo in the ischemic myocardium. The cardiac functions have been considerably improved by Gel@Exo administration, as indicated by the enhancing ejection fraction and fractional shortening, and reducing fibrosis area. Immunofluorescence staining and reverse transcription-polymerase chain reaction (RT-PCR) results demonstrate that the expression of cardiac-related proteins (Cx43, Ki67, CD31, and α-SMA) and genes (VEGF-A, VEGF-B, vWF, TGF-ß1, MMP-9, and Serca2a) are remarkably upregulated. The conductive Gel@Exo system can significantly improve cell-to-cell interactions, promote cell proliferation and angiogenesis, and result in a prominent therapeutic effect on MI-I/R, providing a promising therapeutic method for injured myocardial tissues.

B Cell Lymphoma 2: A Potential Therapeutic Target for Cancer Therapy.

Defects in the apoptosis mechanism stimulate cancer cell growth and survival. B cell lymphoma 2 (Bcl-2) is an anti-apoptotic molecule that plays a central role in apoptosis. Bcl-2 is the founding constituent of the Bcl-2 protein family of apoptosis controllers, the primary apoptosis regulators linked with cancer. Bcl-2 has been identified as being over-expressed in several cancers. Bcl-2 is induced by protein kinases and several signaling molecules which stimulate cancer development. Identifying the important function played by Bcl-2 in cancer progression and development, and treatment made it a target related to therapy for multiple cancers. Among the various strategies that have been proposed to block Bcl-2, BH3-mimetics have appeared as a novel group of compounds thanks to their favorable effects on many cancers within several clinical settings. Because of the fundamental function of Bcl-2 in the regulation of apoptosis, the Bcl-2 protein is a potent target for the development of novel anti-tumor treatments. Bcl-2 inhibitors have been used against several cancers and provide a pre-clinical platform for testing novel therapeutic drugs. Clinical trials of multiple investigational agents targeting Bcl-2 are ongoing. This review discusses the role of Bcl-2 in cancer development; it could be exploited as a potential target for developing novel therapeutic strategies to combat various types of cancers. We further highlight the therapeutic activity of Bcl-2 inhibitors and their implications for the therapeutic management of cancer.

Modular Assembly of Tumor-Penetrating and Oligomeric Nanozyme Based on Intrinsically Self-Assembling Protein Nanocages.

Biomimetic design of nanomaterials with enzyme-like characteristics has emerged as a promising method for the generation of novel therapeutics. However, synthesis of nanomaterials while maintaining a high degree of control over both geometry and valency poses a prominent challenge. Herein, the authors introduce a nanomaterial-based synthetic biology strategy for accurate and quantitative tailoring of high-ordered nanostructures that uses a "bottom-up" hierarchical incorporation of protein building blocks. The assembled nano-oligomers possessed tunable protein motifs and multivalent binding domains, which facilitated prolonged blood circulation time, accumulation within tumor cells through direct targeting of cell receptors, and deep tumor tissue penetration via a transcytosis mechanism. Using these protein/protein nano-oligomers as scaffolds, the authors created a new series of artificial nano-scaled metalloenzymes (nanozymes) by the in situ incorporation of metal nanoclusters within the cavity of the protein nanocages. Nanozymes were capable of mimicking peroxidase-like activity and generated cytotoxic free radicals. Compared to nanozyme alone, the systemic delivery of oligomeric nanozymes demonstrated significantly enhanced therapeutic and anti-tumor benefits. This study shows a new insight into nanotechnology by taking advantage of synthetic biotechnology.

A Natural Alternative Treatment for Urinary Tract Infections: Itxasol©, the Importance of the Formulation.

Genito-urinary tract infections have a high incidence in the general population, being more prevalent among women than men. These diseases are usually treated with antibiotics, but very frequently, they are recurrent and lead to the creation of resistance and are associated with increased morbidity and mortality. For this reason, it is necessary to develop new compounds for their treatment. In this work, our objective is to review the characteristics of the compounds of a new formulation called Itxasol© that is prescribed as an adjuvant for the treatment of UTIs and composed of ß-arbutin, umbelliferon and n-acetyl cysteine. This formulation, based on biomimetic principles, makes Itxasol© a broad-spectrum antibiotic with bactericidal, bacteriostatic and antifungal properties that is capable of destroying the biofilm and stopping its formation. It also acts as an anti-inflammatory agent, without the adverse effects associated with the recurrent use of antibiotics that leads to renal nephrotoxicity and other side effects. All these characteristics make Itxasol© an ideal candidate for the treatment of UTIs since it behaves like an antibiotic and with better characteristics than other adjuvants, such as D-mannose and cranberry extracts.

Multifaceted MRGPRX2: New insight into the role of mast cells in health and disease.

Cutaneous mast cells (MCs) express Mas-related G protein-coupled receptor-X2 (MRGPRX2; mouse ortholog MrgprB2), which is activated by an ever-increasing number of cationic ligands. Antimicrobial host defense peptides (HDPs) generated by keratinocytes contribute to host defense likely by 2 mechanisms, one involving direct killing of microbes and the other via MC activation through MRGPRX2. However, its inappropriate activation may cause pseudoallergy and likely contribute to the pathogenesis of rosacea, atopic dermatitis, allergic contact dermatitis, urticaria, and mastocytosis. Gain- and loss-of-function missense single nucleotide polymorphisms in MRGPRX2 have been identified. The ability of certain ligands to serve as balanced or G protein-biased agonists has been defined. Small-molecule HDP mimetics that display both direct antimicrobial activity and activate MCs via MRGPRX2 have been developed. In addition, antibodies and reagents that modulate MRGPRX2 expression and signaling have been generated. In this article, we provide a comprehensive update on MrgprB2 and MRGPRX2 biology. We propose that harnessing MRGPRX2's host defense function by small-molecule HDP mimetics may provide a novel approach for the treatment of antibiotic-resistant cutaneous infections. In contrast, MRGPRX2-specific antibodies and inhibitors could be used for the modulation of allergic and inflammatory diseases that are mediated via this receptor.

Biomimetic magnetofluorescent ferritin nanoclusters for magnetic resonance and fluorescence-dual modal imaging and targeted tumor therapy.

Multiple imaging by combining magnetic resonance (MR) and fluorescence imaging into a single nanosystem displays distinctive merits, which is desirable for precise in vivo imaging. In this work, we proposed a new tumor-targeting dual-modal diagnosis strategy by designing and fabricating a biocompatible nano-erythrocyte and successfully delivering it into in vivo tumors. The novel nano-contrast agent (CMR) was prepared by encapsulating human heavy-chain ferritin (HFn) nanoparticles with Cy5.5 binding and mineralized iron oxide nanoparticles (Fe3O4 NPs) into erythrocyte membranes (RBCs). We demonstrated that the as-prepared CMR displayed excellent biocompatibility with low hepatotoxicity and long blood circulation time. More importantly, by functionalizing the CMR with different types of targeting moieties, the nanosystem could precisely target both subcutaneous and orthotopic tumors, and exhibited excellent MR and fluorescence dual-model imaging ability. Moreover, we demonstrated that the CMR was able to modulate the tumor microenvironment to achieve an efficient antitumor effect.

Keratan sulfate-based glycomimetics using Langerin as a target for COPD: lessons from studies on Fut8 and core fucose.

Glycosylation represents one of the most abundant posttranslational modification of proteins. Glycosylation products are diverse and are regulated by the cooperative action of various glycosyltransferases, glycosidases, substrates thereof: nucleoside sugars and their transporters, and chaperons. In this article, we focus on a glycosyltransferase, α1,6-fucosyltransferase (Fut8) and its product, the core fucose structure on N-glycans, and summarize the potential protective functions of this structure against emphysema and chronic obstructive pulmonary disease (COPD). Studies of FUT8 and its enzymatic product, core fucose, are becoming an emerging area of interest in various fields of research including inflammation, cancer and therapeutics. This article discusses what we can learn from studies of Fut8 and core fucose by using knockout mice or in vitro studies that were conducted by our group as well as other groups. We also include a discussion of the potential protective functions of the keratan sulfate (KS) disaccharide, namely L4, against emphysema and COPD as a glycomimetic. Glycomimetics using glycan analogs is one of the more promising therapeutics that compensate for the usual therapeutic strategy that involves targeting the genome and the proteome. These typical glycans using KS derivatives as glycomimetics, will likely become a clue to the development of novel and effective therapeutic strategies.

2D LDH-MoS2 clay nanosheets: synthesis, catalase-mimic capacity, and imaging-guided tumor photo-therapy.

Owing to the hypoxia status of the tumor, the reactive oxygen species (ROS) production during photodynamic therapy (PDT) of the tumor is less efficient. Herein, a facile method which involves the synthesis of Mg-Mn-Al layered double hydroxides (LDH) clay with MoS2 doping in the surface and anionic layer space of LDH was presented, to integrate the photo-thermal effect of MoS2 and imaging and catalytic functions of Mg-Mn-Al LDH. The designed LDH-MoS2 (LMM) clay composite was further surface-coated with bovine serum albumin (BSA) to maintain the colloidal stability of LMM in physiological environment. A photosensitizer, chlorin e6 (Ce6), was absorbed at the surface and anionic layer space of LMM@BSA. In the LMM formulation, the magnetic resonance imaging of Mg-Mn-Al LDH was enhanced thanks to the reduced and acid microenvironment of the tumor. Notably, the ROS production and PDT efficiency of Ce6 were significantly improved, because LMM@BSA could catalyze the decomposing of the overexpressed H2O2 in tumors to produce oxygen. The biocompatible LMM@BSA that played the synergism with tumor microenvironment is a promising candidate for the effective treatment of cancer.

Biomimetic Nanoemulsion for Synergistic Photodynamic-Immunotherapy Against Hypoxic Breast Tumor.

Photodynamic therapy (PDT) is commonly used as an "in situ vaccine" to enhance the response rate of PD-1/PD-L1 antibodies. Unfortunately, the high cost and adverse effects of these antibodies, and the hypoxic state of solid tumors limits the efficacy of synergistic photodynamic-immunotherapy. Here, we developed a biomimetic nanoemulsion camouflaged with a PD-1-expressing cell membrane for synergistic photodynamic-immunotherapy against hypoxic breast tumors. The perfluorocarbon of the nanoemulsion could provide oxygen as the source of PDT against hypoxic tumors. Moreover, co-delivering a photosensitizer and the PD-1 protein (substituting for a PD-L1 antibody) achieves the synergy effect of PDT and immunotherapy. Synergistic photodynamic-immunotherapy completely inhibited primary and distant subcutaneous 4T1 tumors, mechanistically by boosting the maturation of dendritic cells and tumor infiltration of cytotoxic T lymphocytes.

Multienzymes activity of metals and metal oxide nanomaterials: applications from biotechnology to medicine and environmental engineering.

With the rapid advancement and progress of nanotechnology, nanomaterials with enzyme-like catalytic activity have fascinated the remarkable attention of researchers, due to their low cost, high operational stability, adjustable catalytic activity, and ease of recycling and reuse. Nanozymes can catalyze the same reactions as performed by enzymes in nature. In contrast the intrinsic shortcomings of natural enzymes such as high manufacturing cost, low operational stability, production complexity, harsh catalytic conditions and difficulties of recycling, did not limit their wide applications. The broad interest in enzymatic nanomaterial relies on their outstanding properties such as stability, high activity, and rigidity to harsh environments, long-term storage and easy preparation, which make them a convenient substitute instead of the native enzyme. These abilities make the nanozymes suitable for multiple applications in sensing and imaging, tissue engineering, environmental protection, satisfactory tumor diagnostic and therapeutic, because of distinguished properties compared with other artificial enzymes such as high biocompatibility, low toxicity, size dependent catalytic activities, large surface area for further bioconjugation or modification and also smart response to external stimuli. This review summarizes and highlights latest progress in applications of metal and metal oxide nanomaterials with enzyme/multienzyme mimicking activities. We cover the applications of sensing, cancer therapy, water treatment and anti-bacterial efficacy. We also put forward the current challenges and prospects in this research area, hoping to extension of this emerging field. In addition to therapeutic potential of nanozymes for disease prevention, their practical effects in diagnostics, to monitor the presence of SARS-CoV-2 and related biomarkers for future pandemics will be predicted.

Enzyme/Nanocopper Hybrid Nanozymes: Modulating Enzyme-like Activity by the Protein Structure for Biosensing and Tumor Catalytic Therapy.

Artificial enzymes with modulated enzyme-mimicking activities of natural systems represent a challenge in catalytic applications. Here, we show the creation of artificial Cu metalloenzymes based on the generation of Cu nanoparticles in an enzyme matrix. Different enzymes were used, and the structural differences between the enzymes especially influenced the controlled the size of the nanoparticles and the environment that surrounds them. Herein, we demonstrated that the oxidase-like catalytic activity of these copper nanozymes was rationally modulated by enzyme used as a scaffold, with a special role in the nanoparticle size and their environment. In this sense, these nanocopper hybrids have confirmed the ability to mimic a unique enzymatic activity completely different from the natural activity of the enzyme used as a scaffold, such as tyrosinase-like activity or as Fenton catalyst, which has extremely higher stability than natural mushroom tyrosinase. More interestingly, the oxidoreductase-like activity of nanocopper hybrids was cooperatively modulated with the synergistic effect between the enzyme and the nanoparticles improving the catalase activity (no peroxidase activity). Additionally, a novel dual (metallic and enzymatic activity) of the nanozyme made the highly improved catechol-like activity interesting for the design of 3,4-dihydroxy-l-phenylalanine (l-DOPA) biosensor for detection of tyrosinase. These hybrids also showed cytotoxic activity against different tumor cells, interesting in biocatalytic tumor therapy.

Evaluation of MicroRNA Therapeutic Potential Using the Mouse In Vivo and Human Ex Vivo Wound Models.

Wound healing is a fundamental physiological process to keep the integrity of the skin; failure of wound healing leads to chronic wounds, which are a common and severe medical problem. MicroRNAs (miRNAs) are gene regulators important for multiple biological functions in the skin, and they play essential roles in different phases of wound repair. Many miRNAs have been found dysregulated in human chronic wounds. Therefore, miRNAs may serve as potential therapeutic targets for wound treatment. In this chapter, we describe a step-by-step protocol about how to evaluate the therapeutic potential of a miRNA in mouse in vivo and human ex vivo wound models. The findings from these preclinical wound models will serve as a basis for further clinical trials.