Biomembrane-Modified Biomimetic Nanodrug Delivery Systems: Frontier Platforms for Cardiovascular Disease Treatment.

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.

Biomimetic Nanoparticles for the Diagnosis and Therapy of Atherosclerosis.

Atherosclerosis (AS) is a chronic inflammation of blood vessels, which often has no obvious symptoms in the early stage of the disease, but when atherosclerotic plaques are formed, they often cause lumen blockage, and even plaque rupture leads to thrombosis, that is the essential factor of cardiovascular events, for example myocardial infarction, cerebral infarction, and renal atrophy. Therefore, it is considerably significant for the early recognition and precise therapy of plaque. Biomimetic nanoparticles (BNPs), especially those coated with cell membranes, can retain the biological function of cell membranes or cells, which has led to extensive research and application in the diagnosis and treatment of AS in recent years. In this review, we summarized the roles of various key cells in AS progression, the construction of biomimetic nanoparticles based on these key cells as well as their applications in AS diagnosis and therapy. Furthermore, we give a challenge and prospect of biomimetic nanoparticles in AS, hoping to elevate their application quality and the possibility of clinical translation.

Advances in biomimetic AIE nanoparticles for diagnosis and phototherapy.

This minireview provides an overview of the recent advancements in the development of biomimetic Aggregation-Induced Emission (AIE) nanoparticles and their applications in disease diagnosis, phototherapy, and photoimmunotherapy. AIE nanoparticles can be engineered to enable efficient image-guided photodynamic and photothermal therapies, however, challenges related to immune defense and target specificity persist. To overcome these, coating biomimetic materials on the surface of AIE nanoparticles, which mimic the features and functions of native cells, have emerged as a promising solution. This minireview will highlight the synthesis strategies and discuss the biomedical application of biomimetic AIE nanoparticles.

Advances in antitumor application of ROS enzyme-mimetic catalysts.

The rapid growth of research on enzyme-mimetic catalysts (Enz-Cats) is expected to promote further advances in nanomedicine for biological detection, diagnosis and treatment of disease, especially tumors. ROS-based nanomedicines present fascinating potential in antitumor therapy owing to the rapid development of nanotechnology. In this review, we focus on the applications of Enz-Cats based on ROS in antitumor therapy. Firstly, the definition and category of ROS are introduced, and the key factors enhancing ROS levels are carefully elucidated. Then, the rationally engineered Enz-Cats via different synthetic approaches with high ROS-producing efficiencies are comprehensively discussed. Subsequently, oncotherapy application of Enz-Cats is comprehensively discussed, which integrates diverse synergistic treatment modalities and exhibits high efficiency in ROS generation. Finally, the challenges and future research direction of this field are presented. This review is dedicated to unraveling the enigmas surrounding the interplay of nanomedicine and organisms.

Biomimetic Ghost Nanomedicine-Based Optotheranostics for Cancer.

Theranostic medicine combines diagnostics and therapeutics, focusing on solid tumors at minimal doses. Optically activated photosensitizers are significant examples owing to their photophysical and chemical properties. Several optotheranostics have been tested that convert light to imaging signals, therapeutic radicals, and heat. Upon light exposure, conjugated photosensitizers kill tumor cells by producing reactive oxygen species and heat or by releasing cancer antigens. Despite clinical trials, these molecularly conjugated photosensitizers require protection from their surroundings and a localized direction for site-specific delivery during blood circulation. Therefore, cell membrane biomimetic ghosts have been proposed for precise and safe delivery of these optically active large molecules, which are clinically relevant because of their biocompatibility, long circulation time, bypass of immune cell recognition, and targeting ability. This review focuses on the role of biomimetic nanoparticles in the treatment and diagnosis of tumors through light-mediated diagnostics and therapy, providing insights into their preclinical and clinical status.

A Review on Tau Targeting Biomimetics Nano Formulations: Novel Approach for Targeting Alzheimer's Diseases.

Central nervous system disorders are prevalent, profoundly debilitating, and poorly managed. Developing innovative treatments for these conditions, including Alzheimer's disease, could significantly improve patients' quality of life and reduce the future economic burden on healthcare systems. However, groundbreaking drugs for central nervous system disorders have been scarce in recent years, highlighting the pressing need for advancements in this field. One significant challenge in the realm of nanotherapeutics is ensuring the precise delivery of drugs to their intended targets due to the complex nature of Alzheimer's disease. Although numerous therapeutic approaches for Alzheimer's have been explored, most drug candidates targeting amyloid-ß have failed in clinical trials. Recent research has revealed that tau pathology can occur independently of amyloid-ß and is closely correlated with the clinical progression of Alzheimer's symptoms. This discovery suggests that tau could be a promising therapeutic target. One viable approach to managing central nervous system disorders is the administration of nanoparticles to neurons, intending to inhibit tau aggregation by directly targeting p-tau. In Alzheimer's disease, beta-amyloid plaques and neurofibrillary tau tangles hinder neuron transmission and function. The disease also triggers persistent inflammation, compromises the blood-brain barrier, leads to brain shrinkage, and causes neuronal loss. While current medications primarily manage symptoms and slow cognitive decline, there is no cure for Alzheimer's.

The Prospect of Biomimetic Immune Cell Membrane-Coated Nanomedicines for Treatment of Serious Bacterial Infections and Sepsis.

Invasive bacterial infections and sepsis are persistent global health concerns, complicated further by the escalating threat of antibiotic resistance. Over the past 40 years, collaborative endeavors to improve the diagnosis and critical care of septic patients have improved outcomes, yet grappling with the intricate immune dysfunction underlying the septic condition remains a formidable challenge. Anti-inflammatory interventions that exhibited promise in murine models failed to manifest consistent survival benefits in clinical studies through recent decades. Novel therapeutic approaches that target bacterial virulence factors, for example with monoclonal antibodies, aim to thwart pathogen-driven damage and restore an advantage to the immune system. A pioneering technology addressing this challenge is biomimetic nanoparticles-a therapeutic platform featuring nanoscale particles enveloped in natural cell membranes. Borne from the quest for a durable drug delivery system, the original red blood cell-coated nanoparticles showcased a broad capacity to absorb bacterial and environmental toxins from serum. Tailoring the membrane coating to immune cell sources imparts unique characteristics to the nanoparticles suitable for broader application in infectious disease. Their capacity to bind both inflammatory signals and virulence factors assembles the most promising sepsis therapies into a singular, pathogen-agnostic therapeutic. This review explores the ongoing work on immune cell-coated nanoparticle therapeutics for infection and sepsis. SIGNIFICANCE STATEMENT: Invasive bacterial infections and sepsis are a major global health problem made worse by expanding antibiotic resistance, meaning better treatment options are urgently needed. Biomimetic cell-membrane-coated nanoparticles are an innovative therapeutic platform that deploys a multifaceted mechanism to action to neutralize microbial virulence factors, capture endotoxins, and bind excessive host proinflammatory cytokines, seeking to reduce host tissue injury, aid in microbial clearance, and improve patient outcomes.

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.

Thrombopoietin mimetic stimulates bone marrow vascular and stromal niches to mitigate acute radiation syndrome.

BACKGROUND: Acute radiation syndrome (ARS) manifests after exposure to high doses of radiation in the instances of radiologic accidents or incidents. Facilitating regeneration of the bone marrow (BM), namely the hematopoietic stem and progenitor cells (HSPCs), is key in mitigating ARS and multi-organ failure. JNJ-26366821, a PEGylated thrombopoietin mimetic (TPOm) peptide, has been shown as an effective medical countermeasure (MCM) to treat hematopoietic-ARS (H-ARS) in mice. However, the activity of TPOm on regulating BM vascular and stromal niches to support HSPC regeneration has yet to be elucidated. METHODS: C57BL/6J mice (9-14 weeks old) received sublethal or lethal total body irradiation (TBI), a model for H-ARS, by 137Cs or X-rays. At 24 h post-irradiation, mice were subcutaneously injected with a single dose of TPOm (0.3 mg/kg or 1.0 mg/kg) or PBS (vehicle). At homeostasis and on days 4, 7, 10, 14, 18, and 21 post-TBI with and without TPOm treatment, BM was harvested for histology, BM flow cytometry of HSPCs, endothelial (EC) and mesenchymal stromal cells (MSC), and whole-mount confocal microscopy. For survival, irradiated mice were monitored and weighed for 30 days. Lastly, BM triple negative cells (TNC; CD45-, TER-119-, CD31-) were sorted for single-cell RNA-sequencing to examine transcriptomics after TBI with or without TPOm treatment. RESULTS: At homeostasis, TPOm expanded the number of circulating platelets and HSPCs, ECs, and MSCs in the BM. Following sublethal TBI, TPOm improved BM architecture and promoted recovery of HSPCs, ECs, and MSCs. Furthermore, TPOm elevated VEGF-C levels in normal and irradiated mice. Following lethal irradiation, mice improved body weight recovery and 30-day survival when treated with TPOm after 137Cs and X-ray exposure. Additionally, TPOm reduced vascular dilation and permeability. Finally, single-cell RNA-seq analysis indicated that TPOm increased the expression of collagens in MSCs to enhance their interaction with other progenitors in BM and upregulated the regeneration pathway in MSCs. CONCLUSIONS: TPOm interacts with BM vascular and stromal niches to locally support hematopoietic reconstitution and systemically improve survival in mice after TBI. Therefore, this work warrants the development of TPOm as a potent radiation MCM for the treatment of ARS.

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.

Biomimetic natural biomaterials for tissue engineering and regenerative medicine: new biosynthesis methods, recent advances, and emerging applications.

Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering (TE) and regenerative medicine. In contrast to conventional biomaterials or synthetic materials, biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix (ECM). Additionally, such materials have mechanical adaptability, microstructure interconnectivity, and inherent bioactivity, making them ideal for the design of living implants for specific applications in TE and regenerative medicine. This paper provides an overview for recent progress of biomimetic natural biomaterials (BNBMs), including advances in their preparation, functionality, potential applications and future challenges. We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM. Moreover, we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications. Finally, we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.

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.

Development of synthetic lipoxin-A4 mimetics (sLXms): New avenues in the treatment of cardio-metabolic diseases.

Resolution of inflammation is a complex, dynamic process consisting of several distinct processes, including inhibition of endothelial activation and leukocyte trafficking; promotion of inflammatory cell apoptosis and subsequent non-phlogistic scavenging and degradation; augmentation of pathogen phagocytosis; modulation of stromal cell phenotype coupled to the promotion of tissue regeneration and repair. Among these tightly regulated processes, the clearance and degradation of apoptotic cells without eliciting an inflammatory response is a crucial allostatic mechanism vital to developmental processes, host defence, and the effective resolution of inflammation. These efferocytic and subsequent effero-metabolism processes can be carried out by professional and non-professional phagocytes. Defective removal or inadequate processing of apoptotic cells leads to persistent unresolved inflammation, which may promote insidious pathologies including scarring, fibrosis, and eventual organ failure. In this manuscript, the well-established role of endothelial activation and leukocyte extravasation, as classical vascular targets of the 'inflammation pharmacology', will be briefly reviewed. The main focus of this work is to bring attention to a less explored aspect of the 'resolution pharmacology', aimed at tackling defective efferocytosis and inefficient effero-metabolism, as key targeted mechanisms to prevent or pre-empt vascular complications in cardio-metabolic diseases. Despite the use of gold standard lipid-lowering drugs or glucose-lowering drugs, none of them are able to tackle the so called residual inflammatory risk and/or the metabolic memory. In this review, the development of synthetic mimetics of endogenous mediators of inflammation is highlighted. Such molecules finely tune key components across the whole inflammatory process, amongst various other novel therapeutic paradigms that have emerged over the past decade, including anti-inflammatory therapy. More specifically, FPR2-agonists in general, and Lipoxin analogues in particular, greatly enhance the reprogramming and cross-talk between classical and non-classical innate immune cells, thus inducing both termination of the pro-inflammatory state as well as promoting the subsequent resolving phase, which represent pivotal mechanisms in inflammatory cardio-metabolic diseases.

Biomimicking Leaf-Vein Engraved Soft and Elastic Membrane Promotes Vascular Reconstruction.

Hierarchical vasculature reconstruction is fundamental for tissue regeneration. The regeneration of functional vascular network requires a proper directional guidance, especially in case of large-size defects. To provide the "running track" for vasculature, a leaf-vein mimetic membrane using soft and elastic poly(lactide-co-propylene glycol-co-lactide) dimethacrylate is developed. Engraved with an interconnected and perfusable leaf-vein micropattern, the membrane can guide human umbilical vein endothelial cells (HUVECs) to form vasculature in vitro. In particular, the "running track" upregulates the angiogenesis-related gene expression and promotes the HUVECs to differentiate into tip cells and stalk cells via tuning vascular endothelial growth factor receptor 2 signaling transduction. As a proof of concept, its revascularization capability using a rat calvarial defect model in vivo is evaluated. The in vivo results demonstrate that the leaf-vein engraved membrane accelerates the formation and maturation of vasculature, leading to a hierarchical blood vessel network. With the superior pro-vasculature property, it is believed that the leaf-vein engraved membrane is not only an ideal candidate for the reconstruction of calvarial vasculature but also a promising solution for more complicated vasculature reconstruction, such as muscle, skin, and heart.

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.

α-Crystallin chaperone mimetic drugs inhibit lens γ-crystallin aggregation: Potential role for cataract prevention.

Γ-Crystallins play a major role in age-related lens transparency. Their destabilization by mutations and physical chemical insults are associated with cataract formation. Therefore, drugs that increase their stability should have anticataract properties. To this end, we screened 2560 Federal Drug Agency-approved drugs and natural compounds for their ability to suppress or worsen H2O2 and/or heat-mediated aggregation of bovine γ-crystallins. The top two drugs, closantel (C), an antihelminthic drug, and gambogic acid (G), a xanthonoid, attenuated thermal-induced protein unfolding and aggregation as shown by turbidimetry fluorescence spectroscopy dynamic light scattering and electron microscopy of human or mouse recombinant crystallins. Furthermore, binding studies using fluorescence inhibition and hydrophobic pocket-binding molecule bis-8-anilino-1-naphthalene sulfonic acid revealed static binding of C and G to hydrophobic sites with medium-to-low affinity. Molecular docking to HγD and other γ-crystallins revealed two binding sites, one in the "NC pocket" (residues 50-150) of HγD and one spanning the "NC tail" (residues 56-61 to 168-174 in the C-terminal domain). Multiple binding sites overlap with those of the protective mini αA-crystallin chaperone MAC peptide. Mechanistic studies using bis-8-anilino-1-naphthalene sulfonic acid as a proxy drug showed that it bound to MAC sites, improved Tm of both H2O2 oxidized and native human gamma D, and suppressed turbidity of oxidized HγD, most likely by trapping exposed hydrophobic sites. The extent to which these drugs act as α-crystallin mimetics and reduce cataract progression remains to be demonstrated. This study provides initial insights into binding properties of C and G to γ-crystallins.

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.