Biomimetic Research Articles

A Versatile Microfluidic Platform for Extravasation Studies Based on DNA Origami-Cell Interactions.

The adhesion of circulating tumor cells (CTCs) to the endothelial lumen and their extravasation to surrounding tissues are crucial in the seeding of metastases and remain the most complex events of the metastatic cascade to study. Integrins expressed on CTCs are major regulators of the extravasation process. This knowledge is primarily derived from animal models and biomimetic systems based on artificial endothelial layers, but these methods have ethical or technical limitations. We present a versatile microfluidic device to study cancer cell extravasation that mimics the endothelial barrier by using a porous membrane functionalized with DNA origami nanostructures (DONs) that display nanoscale patterns of adhesion peptides to circulating cancer cells. The device simulates physiological flow conditions and allows direct visualization of cell transmigration through microchannel pores using 3D confocal imaging. Using this system, we studied integrin-specific adhesion in the absence of other adhesive events. Specifically, we show that the transmigration ability of the metastatic cancer cell line MDA-MB-231 is influenced by the type, distance, and density of adhesion peptides present on the DONs. Furthermore, studies with mixed ligand systems indicate that integrins binding to RGD (arginine-glycine-aspartic acid) and IDS (isoleucine-aspartic acid-serine) did not synergistically enhance the extravasation process of MDA-MB-231 cells.

A Versatile Microfluidic Platform for Extravasation Studies Based on DNA Origami—Cell Interactions

AbstractThe adhesion of circulating tumor cells (CTCs) to the endothelial lumen and their extravasation to surrounding tissues are crucial in the seeding of metastases and remain the most complex events of the metastatic cascade to study. Integrins expressed on CTCs are major regulators of the extravasation process. This knowledge is primarily derived from animal models and biomimetic systems based on artificial endothelial layers, but these methods have ethical or technical limitations. We present a versatile microfluidic device to study cancer cell extravasation that mimics the endothelial barrier by using a porous membrane functionalized with DNA origami nanostructures (DONs) that display nanoscale patterns of adhesion peptides to circulating cancer cells. The device simulates physiological flow conditions and allows direct visualization of cell transmigration through microchannel pores using 3D confocal imaging. Using this system, we studied integrin‐specific adhesion in the absence of other adhesive events. Specifically, we show that the transmigration ability of the metastatic cancer cell line MDA‐MB‐231 is influenced by the type, distance, and density of adhesion peptides present on the DONs. Furthermore, studies with mixed ligand systems indicate that integrins binding to RGD (arginine‐glycine‐aspartic acid) and IDS (isoleucine‐aspartic acid‐serine) did not synergistically enhance the extravasation process of MDA‐MB‐231 cells.

Remotely Controlled 3D-Engineered Scaffolds for Biomimetic In Vitro Investigations on Brain Cell Cocultures.

Most in vitro studies regarding new anticancer treatments are performed on 2D cultures, despite this approach imposes several limitations in recapitulating the real tumor behavior and in predicting the effects of therapy on both cancer and healthy tissues. Herein, advanced in vitro models based on scaffolds that support the 3D growth of glioma cells, further allowing the cocultures with healthy brain cells, are presented. These scaffolds, doped with superparamagnetic iron oxide nanoparticles and obtained through 2-photon polymerization, can be remotely manipulated thanks to an external magnet, thus obtaining biomimetic 3D organization recapitulating the brain cancer microenvironment. From a geometric point of view, the structure is functional to both cell culture on individual unit scaffolds and to tailored cocultures fostered by magnetic-driven unit assembly, also allowing for cell migration thanks to passages/fenestrations on adjacent structures. Leveraging magnetic dragging, for which a mathematical model is introduced, multiple cocultures are achieved, highlighting the high versatility and the user-friendly character of the proposed platform that can help overcome the current challenges in 3D cocultures handling, and open the way to the construction of increasingly biomimetic artificial systems.

Highly Promising 2D/1D BP-C/CNT Bionic Opto-Olfactory Co-Sensory Artificial Synapses for Multisensory Integration.

The development of high-performance artificial synaptic neuromorphic devices poses a significant challenge in the creation of biomimetic sensing neural systems that seamlessly integrate both sensory and computational functionalities. In pursuit of this objective, promising bionic opto-olfactory co-sensory artificial synapse devices are constructed utilizing the BP-C/CNT (2D/1D) hybrid filter membrane as the resistive layer. Experimental results demonstrated that the devices seamlessly integrated the light modulation, gas detection, and biological synaptic functions into a single device while addressing the challenge with separating artificial synaptic devices from sensors. These devices offered the following advantages: 1) Simulating visual synapses, they can effectively replicate fundamental synaptic functions under both electrical and optical stimulation. 2) By emulating olfactory synapse responses to specific gases, they can achieve ultra-low detection limits and rapid identification of ethanol and acetone gases. 3) They enable photo-olfactory co-sensing simulations that mimic synaptic function under light-modulated pulse conditions in distinct gas environments, facilitating the study of synaptic learning rules and Pavlovian responses. This work provides a pioneering approach for exploring highly stable 2D BP-based optoelectronics and advancing the development of biomimetic neural systems.

A biomimetic lubricating nanosystem for synergistic therapy of osteoarthritis

Failure of articular cartilage lubrication and inflammation are the main causes of osteoarthritis (OA), and integrated treatment realizing joint lubrication and anti-inflammation is becoming the most effective treat model. Inspired by low friction of human synovial fluid and adhesive chemical effect of mussels, our work reports a biomimetic lubricating system that realizes long-time lubrication, photothermal responsiveness and anti-inflammation property. To build the system, a dopamine-mediated strategy is developed to controllably graft hyaluronic acid on the surface of metal organic framework. The design constructs a biomimetic core–shell structure that has good dispersity and stability in water with a high drug loading ratio of 99%. Temperature of the solution rapidly increases to 55 °C under near-infrared light, and the hard-soft lubricating system well adheres to wear surfaces, and greatly reduces frictional coefficient by 75% for more than 7200 times without failure. Cell experiments show that the nanosystem enters cells by endocytosis, and releases medication in a sustained manner. The anti-inflammatory outcomes validate that the nanosystem prevents the progression of OA by down-regulating catabolic proteases and pain-related genes and up-regulating genes that are anabolic in cartilage. The study provides a bioinspired strategy to employ metal organic framework with controlled surface and structure for friction reduction and anti-inflammation, and develops a new concept of OA synergistic therapy model for practical applications.

Targeted Delivery of Macrophage Membrane Biomimetic Liposomes Through Intranasal Administration for Treatment of Ischemic Stroke.

Ginsenoside Rg3 (Rg3) and Panax notoginseng saponins (PNS) can be used for ischemic stroke treatment, however, the lack of targeting to the ischemic region limits the therapeutic effect. To address this, we leveraged the affinity of macrophage membrane proteins for inflamed brain microvascular endothelial cells to develop a macrophage membrane-cloaked liposome loaded with Rg3 and PNS (MM-Lip-Rg3/PNS), which can precisely target brain lesion region through intranasal administration. MM-Lip-Rg3/PNS was prepared by co-extrusion method and was performed by characterization, stability, surface protein, and morphology. The cellular uptake, immune escape ability, and blood-brain barrier crossing ability of MM-Lip-Rg3/PNS were studied in vitro. The in vivo brain targeting, biodistribution and anti-ischemic efficacy of MM-Lip-Rg3/PNS were evaluated in MACO rats, and we determined the diversity of the nasal brain pathway through the olfactory nerve blockade model in rats. Finally, the pharmacokinetics and brain targeting index of MM-Lip-Rg3/PNS were investigated. Our results indicated that MM-Lip-Rg3/PNS was spherical with a shell-core structure. MM-Lip-Rg3/PNS can avoid mononuclear phagocytosis, actively bind to inflammatory endothelial cells, and have the ability to cross the blood-brain barrier. Moreover, MM-Lip-Rg3/PNS could specifically target ischemic sites, even microglia, increase the cumulative number of drugs in the brain, improve the inflammatory environment of the brain, and reduce the infarct size. By comparing olfactory nerve-blocking rats with normal rats, it was found that there are direct and indirect pathways for nasal entry into the brain. Pharmacokinetics demonstrated that MM-Lip-Rg3/PNS exhibited stronger brain targeting and prolonged drug half-life. MM-Lip-Rg3/PNS might contribute to the accumulation of Rg3 and PNS in the ischemic brain area to improve treatment efficacy. This biomimetic nano-drug delivery system provides a new and promising strategy for the treatment of ischemic stroke.

Biomimic and bioinspired soft neuromorphic tactile sensory system

The progress in flexible and neuromorphic electronics technologies has facilitated the development of artificial perception systems. By closely emulating biological functions, these systems are at the forefront of revolutionizing intelligent robotics and refining the dynamics of human–machine interactions. Among these, tactile sensory neuromorphic technologies stand out for their ability to replicate the intricate architecture and processing mechanisms of the brain. This replication not only facilitates remarkable computational efficiency but also equips devices with efficient real-time data-processing capability, which is a cornerstone in artificial intelligence evolution and human–machine interface enhancement. Herein, we highlight recent advancements in neuromorphic systems designed to mimic the functionalities of the human tactile sensory system, a critical component of somatosensory functions. After discussing the tactile sensors which biomimic the mechanoreceptors, insights are provided to integrate artificial synapses and neural networks for advanced information recognition emphasizing the efficiency and sophistication of integrated system. It showcases the evolution of tactile recognition biomimicry, extending beyond replicating the physical properties of human skin to biomimicking tactile sensations and efferent/afferent nerve functions. These developments demonstrate significant potential for creating sensitive, adaptive, plastic, and memory-capable devices for human-centric applications. Moreover, this review addresses the impact of skin-related diseases on tactile perception and the research toward developing artificial skin to mimic sensory and motor functions, aiming to restore tactile reception for perceptual challenged individuals. It concludes with an overview of state-of-the-art biomimetic artificial tactile systems based on the manufacturing–structure–property–performance relationships, from devices mimicking mechanoreceptor functions to integrated systems, underscoring the promising future of artificial tactile sensing and neuromorphic device innovation.

Four-Dimensional Printing as A Technology Based on Bio Mimicry to Produce Spaces that Interact with The Surrounding Environment

Four-Dimensional Printing as A Technology Based on Bio Mimicry to Produce Spaces that Interact with The Surrounding Environment

Synthetic Condensates and Cell-Like Architectures from Amphiphilic DNA Nanostructures.

Synthetic droplets and condensates are becoming increasingly common constituents of advanced biomimetic systems and synthetic cells, where they can be used to establish compartmentalization and sustain life-like responses. Synthetic DNA nanostructures have demonstrated significant potential as condensate-forming building blocks owing to their programmable shape, chemical functionalization, and self-assembly behavior. We have recently demonstrated that amphiphilic DNA "nanostars", obtained by labeling DNA junctions with hydrophobic moieties, constitute a particularly robust and versatile solution. The resulting amphiphilic DNA condensates can be programmed to display complex, multi-compartment internal architectures, structurally respond to various external stimuli, synthesize macromolecules, capture and release payloads, undergo morphological transformations, and interact with live cells. Here, we demonstrate protocols for preparing amphiphilic DNA condensates starting from constituent DNA oligonucleotides. We will address (i) single-component systems forming uniform condensates, (ii) two-component systems forming core-shell condensates, and (iii) systems in which the condensates are modified to support in vitro transcription of RNA nanostructures.

Modelling chemotherapy-induced cardiotoxicity with live myocardial slices: from bedside to bench and back again

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Netherlands Heart Institute & Dutch Heart Foundation (Dekker Senior Clinical Scientist 2019) Introduction Cancer therapy related cardiac dysfunction (CTRCD) is a common side-effect of many oncological regimens. The prevention, diagnosis and treatment of CTRCD requires a well-orchestrated management by a multidisciplinary team composed by oncologists, cardiologists, radiologists, but less often translational scientists. Purpose In this work, we investigated the translational potential of live myocardial slices derived from a patient presenting with acute biventricular failure, with no history of cardiovascular disease, who had previously received neo-adjuvant chemotherapy containing doxorubicin (240 mg/m2) and trastuzumab, for the treatment of a breast carcinoma. In contrast to anthracycline cardiotoxicity, which is often permanent, cardiac dysfunction caused by trastuzumab is commonly reversible after cessation of treatment. Herein, we provide a novel side-by-side comparison of myocardial function ex vivo and clinical outcomes in the patient. Methods After several days on extracorporeal life support and inotropic therapy, the patient’s cardiac function did not improve. The patient was ultimately implanted with a left- and right-ventricular assist device (LVAD and RVAD, respectively). Live myocardial slices were produced from the apical biopsy obtained during LVAD implantation and cultured in a biomimetic system under physiological mechanical and electrical conditions. Slices were subsequently exposed to doxorubicin, trastuzumab or vehicle (0.1% DMSO) for a continued period of 7 days. Contractile force was recorded continuously, and a custom-made stimulation protocol applied every 24h. To evaluate responsiveness to inotropes, slices were incubated with milrinone before culture termination. Calcium transients and action potentials were determined optically using calcium and voltage-sensitive dyes. Results Continued exposure to either doxorubicin or trastuzumab limited the recovery of contractility in myocardial slices. In contrast, vehicle controls showed a robust recovery and development of stronger contractile forces. Doxorubicin-treated slices were less responsive to stimulation, displayed increased stimulation threshold and were less able to follow pacing at higher frequencies. Optical mapping revealed that exposure to doxorubicin led to the development of abnormal calcium handling. In parallel to the ex vivo findings, RVAD/LVAD-mediated cardiac unloading and the absence of any chemotherapy drug, resulted in a significant recovery of right-ventricular function, enabling RVAD removal within 2 weeks. Conclusions The complex nature of chemotherapy-induced cardiotoxicity imposes numerous challenges in clinical decision-making. In this unique case, patient care could be paralleled by concomitant state-of-the-art ex vivo tissue culture. We observed that myocardial tissue slices could partially recapitulate clinical observations, highlightings the promising synergy between translational science and personalized patient care.

A combination of a TLR7/8 agonist and an epigenetic inhibitor suppresses triple-negative breast cancer through triggering anti-tumor immune

BackgroundCombination therapy involving immune checkpoint blockade (ICB) and other drugs is a potential strategy for converting immune-cold tumors into immune-hot tumors to benefit from immunotherapy. To achieve drug synergy, we developed a homologous cancer cell membrane vesicle (CM)-coated metal-organic framework (MOF) nanodelivery platform for the codelivery of a TLR7/8 agonist with an epigenetic inhibitor.MethodsA novel biomimetic codelivery system (MCM@UN) was constructed by MOF nanoparticles UiO-66 loading with a bromodomain-containing protein 4 (BRD4) inhibitor and then coated with the membrane vesicles of homologous cancer cells that embedding the 18 C lipid tail of 3M-052 (M). The antitumor immune ability and tumor suppressive effect of MCM@UN were evaluated in a mouse model of triple-negative breast cancer (TNBC) and in vitro. The tumor immune microenvironment was analyzed by multicolor immunofluorescence staining.ResultsIn vitro and in vivo data showed that MCM@UN specifically targeted to TNBC cells and was superior to the free drug in terms of tumor growth inhibition and antitumor immune activity. In terms of mechanism, MCM@UN blocked BRD4 and PD-L1 to prompt dying tumor cells to disintegrate and expose tumor antigens. The disintegrated tumor cells released damage-associated molecular patterns (DAMPs), recruited dendritic cells (DCs) to efficiently activate CD8+ T cells to mediate effective and long-lasting antitumor immunity. In addition, TLR7/8 agonist on MCM@UN enhanced lymphocytes infiltration and immunogenic cell death and decreased regulatory T-cells (Tregs). On clinical specimens, we found that mature DCs infiltrating tumor tissues of TNBC patients were negatively correlated with the expression of BRD4, which was consistent with the result in animal model.ConclusionMCM@UN specifically targeted to TNBC cells and remodeled tumor immune microenvironment to inhibit malignant behaviors of TNBC.

Emulation and evaluation of tumor cell combined chemotherapy in isotropic/anisotropic collagen fiber microenvironments.

The rapid emergence of anisotropic collagen fibers in the tissue microenvironment is a critical transition point in late-stage breast cancer. Specifically, the fiber orientation facilitates the likelihood of high-speed tumor cell invasion and metastasis, which pose lethal threats to patients. Thus, based on this transition point, one key issue is how to determine and evaluate efficient combination chemotherapy treatments in late-stage cancer. In this study, we designed a collagen microarray chip containing 241 high-throughput microchambers with embedded metastatic breast cancer cell MDA-MB-231-RFP. By utilizing collagen's unique structure and hydromechanical properties, the chip constructed three-dimensional isotropic and anisotropic collagen fiber structures to emulate the tumor cell microenvironment at early and late stages. We injected different chemotherapeutic drugs into its four channels and obtained composite biochemical concentration profiles. Our results demonstrate that anisotropic collagen fibers promote cell proliferation and migration more than isotropic collagen fibers, suggesting that the geometric arrangement of fibers plays an important role in regulating cell behavior. Moreover, the presence of anisotropic collagen fibers may be a potential factor leading to the poor efficacy of combined chemotherapy in late-stage breast cancer. We investigated the efficacy of various chemotherapy drugs using cell proliferation inhibitors paclitaxel and gemcitabine and tumor cell migration inhibitors 7rh and PP2. To ensure the validity of our findings, we followed a systematic approach that involved testing the inhibitory effects of these drugs. According to our results, the drug combinations' effectiveness could be ordered as follows: paclitaxel + gemcitabine > gemcitabine + 7rh > PP2 + paclitaxel > 7rh + PP2. This study shows that the biomimetic chip system not only facilitates the creation of a realistic in vitro model for examining the cell migration mechanism in late-stage breast cancer but also has the potential to function as an effective tool for future chemotherapy assessment and personalized medicine.

Integrated analysis of electroosmotic and magnetohydrodynamic peristaltic pumping in physiological systems: Implications for biomedical applications

AbstractThe study of rheological properties in biological fluids, influenced by electroosmosis and magnetohydrodynamic (MHD) peristaltic mechanisms, plays a vital role in designing micro‐scale biomimetic pumping systems for targeted drug delivery. Considering these significant applications, the current study focuses on the integrated analysis of electroosmotic and magnetohydrodynamic peristaltic pumping of Williamson fluid within physiological systems with variable viscosity and thermal conductivity. The dimensional momentum equations are linearized under the approximation of lubrication theory. The current study deals with the impact of various physical parameters on flow, heat transfer, and pumping characteristics. These parameters include the magnetic parameter, variable viscosity, variable thermal conductivity, Helmholtz‐Smoluchowski velocity, and so on. It is noted from the current analysis that, Helmholtz‐Smoluchowski velocity and velocity slip parameters have decreasing effect on skin friction and Sherwood number. The electroosmotic and magnetic parameters contribute to larger trapped bolus sizes. These findings contribute significantly to advancing the development of efficient micro‐scale biomimetic pumping systems tailored for precise target drug delivery applications.

Synthetic Biomimetic Liposomes Harness Efferocytosis Machinery for Highly Efficient Macrophages-Targeted Drug Delivery to Alleviate Inflammation.

Macrophages play pivotal roles in the regulation of inflammatory responses and tissue repair, making them a prime target for inflammation alleviation. However, the accurate and efficient macrophages targeting is still a challenging task. Motivated by the efficient and specific removal of apoptotic cells by macrophages efferocytosis, a novel biomimetic liposomal system called Effero-RLP (Efferocytosis-mediated Red blood cell hybrid Liposomes) is developed which incorporates the membrane of apoptotic red blood cells (RBCs) with liposomes for the purpose of highly efficient macrophages targeting. Rosiglitazone (ROSI), a PPARγ agonist known to attenuate macrophage inflammatory responses, is encapsulated into Effero-RLP as model drug to regulate macrophage functions in DSS-induced colitis mouse model. Intriguingly, the Effero-RLP exhibits selective and efficient uptake by macrophages, which is significantly inhibited by the efferocytosis blocker Annexin V. In animal models, the Effero-RLP demonstrates rapid recognition by macrophages, leading to enhanced accumulation at inflammatory sites. Furthermore, ROSI-loaded Effero-RLP effectively alleviates inflammation and protects colon tissue from injury in the colitis mouse model, which is abolished by deletion of macrophages from mice model. In conclusion, the study highlights the potential of macrophage targeting using efferocytosis biomimetic liposomes. The development of Effero-RLP presents novel and promising strategies for alleviating inflammation.

Advances in Tumor Targeting Biomimetic Drug Delivery Systems: A Promising Approach for Antitumor Therapy

AbstractCancer is one of the most fatal diseases that attract numerous efforts and attention from researchers. Among plentiful therapeutic agents, chemotherapy is frequently used in treating virulent tumors, and its insistent administration is useful in the ablation of cancers; however, it also produces side effects. Biomimetic drug delivery systems (BDDSs) provide an alternative route for antitumor therapy. Their endogenous substances may be extracellular vesicles, living cells, cell membranes, etc., which optimize single-agent chemotherapy. They “upgrade” traditional drug delivery platforms by combining the original drug with itself, disguised as a Trojan Horse, to trick the immune system or tumor tissues to achieve higher targeting and lower immunogenicity. Herein, we review three BDDS strategies being used recently in antitumor drug development and their advances, aiming at providing general guidelines and opportunities in this field in the future.

Selected Chromatographic Methods for Determining the Biological Activity of Substances

This paper presents various aspects of the use of chromatography to determine the biological activity of substances. On the one hand, the use of chromatography to determine the lipophilicity of a substance, a property that affects all LADME steps in various biomimetic systems, is presented, using various descriptors such as the retention factor in pure water (or buffer with physiological plasma pH), the CHI value, and Chrom logD. The use of chromatography in biomimetic systems to determine the interaction of substances with phospholipids (IAM stationary phases) and transport proteins (stationary phases with immobilised proteins) is also discussed. On the basis of the retention data obtained in these systems, the volume of distribution of the substance and the degree of binding of the substance with the proteins in question can be determined. Chromatography is also a method used to determine the interaction of substances with specific membrane receptors at their site of action using membrane chromatography (MCM). Thanks to biological detection, chromatography can also be used to determine the antimicrobial activity (bioautography) of substances and the effect of substances on biochemical reactions taking place in organisms, such as antioxidant properties and the inhibitory activity of various enzymes (biological assay).

Research on key technology of cooled infrared bionic compound eye camera based on small lens array

Traditional 2D imaging technologies are limited by the need for a large field of view and their sensitivity to small target motion. Inspired by the characteristics of insect compound eye structure, we propose an infrared bionic compound eye camera based on a small lens array. The camera is composed of 61 small lens arrays mounted on a curved spherical shell and a relay optical system. The imaging device is a high-performance cooled mid-wave infrared detector. This is an innovative design for an infrared biomimetic compound eye camera system that provides a wide field of view and all-day detection capability. Aimed to meet the specified requirements. The optical system achieves a 100% cold-membrane match between the infrared optical system and the cooled detector, and the relay optical system optimizes the large-field aberration by introducing a higher-order aspheric surface and modifying the geometric surface of the lenses. Our entire system enables an observation field angle of 108∘×108∘\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$108^\\circ \ imes 108^\\circ$$\\end{document}. The experiments showed that the image quality of the system is high, each ommatidium was effective within the imaging range of the compound eye camera, resulting in an improved signal-to-noise ratio in various scenes.

Mesoporous MOFs with ROS scavenging capacity for the alleviation of inflammation through inhibiting stimulator of interferon genes to promote diabetic wound healing

Excessive production of reactive oxygen species (ROS) and inflammation are the key problems that impede diabetic wound healing. In particular, dressings with ROS scavenging capacity play a crucial role in the process of chronic wound healing. Herein, Zr-based large-pore mesoporous metal–organic frameworks (mesoMOFs) were successfully developed for the construction of spatially organized cascade bioreactors. Natural superoxide dismutase (SOD) and an artificial enzyme were spatially organized in these hierarchical mesoMOFs, forming a cascade antioxidant defense system, and presenting efficient intracellular and extracellular ROS scavenging performance. In vivo experiments demonstrated that the SOD@HMUiO-MnTCPP nanoparticles (S@M@H NPs) significantly accelerated diabetic wound healing. Transcriptomic and western blot results further indicated that the nanocomposite could inhibit fibroblast senescence and ferroptosis as well as the stimulator of interferon genes (STING) signaling pathway activation in macrophages mediated by mitochondrial oxidative stress through ROS elimination. Thus, the biomimetic multi-enzyme cascade catalytic system with spatial ordering demonstrated a high potential for diabetic wound healing, where senescence, ferroptosis, and STING signaling pathways may be potential targets.Graphical Schematic diagram showing the proposed mechanism that S@M@H NPs promoted diabetic wound healing

Electronic inductive and resonance effects of substituents on concerted two-proton-coupled electron transfer between electrogenerated superoxide and hydroquinone derivatives in N,N-dimethylformamide

Improving energy conversion technologies is pivotal for reducing the effects of global warming. The use of electron transfer catalysts based on electron carriers found in organisms, such as redox biomimetic quinone systems, is a promising route for truly efficient energy conversion. Herein, we report the density functional theory (DFT)-based analysis of the reaction between electrogenerated superoxide radical anion (O2•−) and methyl- or chloro-substituted benzene-1,4-diol (hydroquinone) derivatives in N,N-dimethylformamide. We investigate the electrochemical scavenging of O2•− by hydroquinone derivatives involving two proton transfers (PTs) and one electron transfer (ET). We show that chloro and methyl substituents promote a proton-coupled electron transfer (PCET) reaction with the effect increasing with the number of substituent groups. Our DFT results demonstrate that the substituent effect promotes either of the PT or ET processes, along a sequential PCET pathway. The electrochemical and DFT analyses of the substituent effect indicate that the concerted two-proton-coupled electron transfer (2PCET) promoted by an increasing number of the substituents is a plausible pathway for the reaction between electrogenerated O2•− and hydroquinone derivatives. In addition, our findings show that the resonance effect is the main driving force for the promotion of 2PCET.

Enhanced breast cancer treatment using phototherapy and RNS therapy with macrophage membrane-coated liposomes

Breast cancer, the predominant malignancy afflicting women, continues to pose formidable challenges despite advancements in therapeutic interventions. This study elucidates the potential of phototherapy, comprising both photothermal and photodynamic therapy (PTT/PDT), as a novel and promising modality. To achieve this goal, we devised liposomes coated with macrophage cell membranes including macrophage-associated membrane proteins, which have demonstrated promise in biomimetic delivery systems for targeting tumors while preserving their inherent tumor-homing capabilities. This integrated biomimetic delivery system comprised IR780, NONOate, and perfluorocarbon. This strategic encapsulation aims to achieve a synergistic combination of photodynamic therapy (PDT) and reactive nitrogen species (RNS) therapy. Under near-infrared laser irradiation at 808 nm, IR780 demonstrates its ability to prolifically generate reactive oxygen species (ROS), including superoxide anion (O2•−), singlet oxygen, and hydroxyl radical (·OH). Simultaneously, NONOate releases nitric oxide (NO) gas upon the same laser irradiation, thereby engaging with IR780-induced ROS to facilitate the formation of peroxynitrite anion (ONOO−), ultimately inducing programmed cell death in cancer cells. Additionally, the perfluorocarbon component of our delivery system exhibits a notable affinity for oxygen and demonstrates efficient oxygen-carrying capabilities. Our results demonstrate that IR780-NO-PFH-Lip@M significantly enhances breast cancer cell toxicity, reducing proliferation and in vivo tumor growth through simultaneous heat, ROS, and RNS production. This study contributes valuable insights to the ongoing discourse on innovative strategies for advancing cancer therapeutics.