Divergent Synthesis of 17-nor-Cephalotane Diterpenoids through Developed Ynol-diene Cyclization.

On the basis of a novel ynol-diene cyclization developed as a rapid access to tropone unit, the first divergent strategy to 17-nor-cephalotane diterpenoids has been successfully established. Combining with a bioinspired stereoselective dual hydrogenation, the divergent total synthesis of (+)-3-deoxyfortalpinoid F, (+)-harringtonolide, (-)-fortalpinoids M/N/P, and analog (-)-20-deoxocephinoid P have been achieved in 14-17 linear longest steps starting from commercially available materials.

Red blood cells based nanotheranostics: A smart biomimetic approach for fighting against cancer.

The technique of engineering drug delivery vehicles continues to develop, which bring enhancements in working more efficiently and minimizing side effects to make it more effective and safer. The intense capability of therapeutic agents to remain undamaged in a harsh extracellular environment is helpful to the success of drug development efforts. With this in mind, alterations of biopharmaceuticals with enhanced stability and decreased immunogenicity have been an increasingly active focus of such efforts. Red blood cells (RBCs), also known as erythrocytes have undergone extensive scrutiny as potential vehicles for drug delivery due to their remarkable attributes over the years of research. These include intrinsic biocompatibility, minimal immunogenicity, flexibility, and prolonged systemic circulation. Throughout the course of investigation, a diverse array of drug delivery platforms based on RBCs has emerged. These encompass genetically engineered RBCs, non-genetically modified RBCs, and RBC membrane-coated nanoparticles, each devised to cater to a range of biomedical objectives. Given their prevalence in the circulatory system, RBCs have gained significant attention for their potential to serve as biomimetic coatings for artificial nanocarriers. By virtue of their surface emulation capabilities and customizable core materials, nanocarriers mimicking these RBCs, hold considerable promise across a spectrum of applications, spanning drug delivery, imaging, phototherapy, immunomodulation, sensing, and detection. These multifaceted functionalities underscore the considerable therapeutic and diagnostic potential across various diseases. Our proposed review provides the synthesis of recent strides in the theranostic utilization of erythrocytes in the context of cancer. It also delves into the principal challenges and prospects intrinsic to this realm of research. The focal point of this review pertains to accentuating the significance of erythrocyte-based theranostic systems in combating cancer. Furthermore, it precisely records the latest and the most specific methodologies for tailoring the attributes of these biomimetic nanoscale formulations, attenuating various discoveries for the treatment and management of cancer.

Biocompatibility of mussel-inspired water-soluble tissue adhesives.

Wound closure in surgeries is traditionally achieved using invasive methods such as sutures and staples. Adhesion-based wound closure methods such as tissue adhesives, sealants, and hemostats are slowly replacing these methods due to their ease of application. Although several chemistries have been developed and used commercially for wound closure, there is still a need for better tissue adhesives from the point of view of toxicity, wet-adhesion strength, and long-term bonding. Catechol chemistry has shown great promise in developing wet-set adhesives that meet these criteria. Herein, we have studied the biocompatibility of a catechol-based copolymer adhesive, poly([dopamine methacrylamide]-co-[methyl methacrylate]-co-[poly(ethylene glycol) methyl ether methacrylate]) or poly(catechol-MMA-OEG), which is soluble in water. The adhesive was injected subcutaneously in a mouse model on its own and in combination with a sodium periodate crosslinker. After 72 h, 4 weeks, and 12 weeks, the mice were euthanized and subjected to histopathological analysis. Both adhesives were present and still palpable at the end of 12 weeks. The moderate inflammation observed for the poly(catechol-MMA-OEG) cohort at 72 h had reduced to mild inflammation at the end of 12 weeks. However, the moderate inflammatory response observed for the poly(catechol-MMA-OEG) + crosslinker cohort at 72 h had not subsided at 12 weeks.

A soft, fatigue-free, and self-healable ionic elastomer via the synergy of skin-like assembly and Bouligand structure.

Soft ionic elastomers that are self-healable, fatigue-free, and environment-tolerant are ideal structural and sensing materials for artificial prosthetics, soft electronics, and robotics to survive unpredictable service conditions. However, most synthetic strategies failed to unite rapid healing, fatigue resistance, and environmental robustness, limited by their singular compositional/structural designs. Here, we present a soft, tough, fatigue-resistant, and self-healable ionic elastomer (STFSI elastomer), which fuses skin-like binary assembly and Bouligand helicoidal structure into a composite of thermoplastic polyurethane (TPU) fibers and a supramolecular ionic biopolymer. The interlocked binary assembly enables skin-like softness, high stretchability, and strain-adaptive stiffening through a matrix-to-scaffold stress transfer. The Bouligand structure contributes to superhigh fracture toughness (101.6 kJ m-2) and fatigue resistance (4937 J m-2) via mechanical toughening by interlayer slipping and twisted crack propagation path. Besides, the STFSI elastomer is self-healable through a "bridging" method and environment-tolerant (-20 ˚C ~ 60 ˚C, strong acid/alkali, saltwater). To demonstrate the versatile structural and sensing applications, we showcase a safety cushion with efficient damping and suppressed rebounding, and a robotic sensor with excellent fatigue crack tolerance and instant sensation recovery upon cutting-off damage. Our presented synthetic strategy is generalizable to other fiber-reinforced tough polymers for applications involving demanding mechanical/environmental conditions.

CeO2 In Situ Growth on Red Blood Cell Membranes: CQD Coating and Multipathway Alzheimer's Disease Therapy under NIR.

Alzheimer's disease (AD) has a complex etiology and diverse pathological processes. The therapeutic effect of single-target drugs is limited, so simultaneous intervention of multiple targets is gradually becoming a new research trend. Critical stages in AD progression involve amyloid-ß (Aß) self-aggregation, metal-ion-triggered fibril formation, and elevated reactive oxygen species (ROS). Herein, red blood cell membranes (RBC) are used as templates for the in situ growth of cerium oxide (CeO2) nanocrystals. Then, carbon quantum dots (CQDs) are encapsulated to form nanocomposites (CQD-Ce-RBC). This strategy is combined with photothermal therapy (PTT) for AD therapy. The application of RBC enhances the materials' biocompatibility and improves immune evasion. RBC-grown CeO2, the first application in the field of AD, demonstrates outstanding antioxidant properties. CQD acts as a chelating agent for copper ions, which prevents the aggregation of Aß. In addition, the thermal effect induced by near-infrared laser-induced CQD can break down Aß fibers and improve the permeability of the blood-brain barrier. In vivo experiments on APP/PS1 mice demonstrate that CQD-Ce-RBC combined with PTT effectively clears cerebral amyloid deposits and significantly enhances learning and cognitive abilities, thereby retarding disease progression. This innovative multipathway approach under light-induced conditions holds promise for AD treatment.

Reduction of Oxidative Stress and Excitotoxicity by Mesenchymal Stem Cell Biomimetic Co-Delivery System for Cerebral Ischemia-Reperfusion Injury Treatment.

A cerebral ischemia-reperfusion injury is ensued by an intricate interplay between various pathological processes including excitotoxicity, oxidative stress, inflammation, and apoptosis. For a long time, drug intervention policies targeting a single signaling pathway have failed to achieve the anticipated clinical efficacy in the intricate and dynamic inflammatory environment of the brain. Moreover, inadequate targeted drug delivery remains a significant challenge in cerebral ischemia-reperfusion injury therapy. In this study, a multifunctional nanoplatform (designated as PB-006@MSC) is developed using ZL006-loaded Prussian blue nanoparticles (PBNPs) camouflaged by a mesenchymal stem cell (MSC) membrane (MSCm). ZL006 is a neuroprotectant. It can be loaded efficiently into the free radical scavenger PBNP through mesoporous adsorption. This can simultaneously modulate multiple targets and pathways. MSCm biomimetics can reduce the nanoparticle immunogenicity, efficiently enhance their homing capability to the cerebral ischemic penumbra, and realize active-targeting therapy for ischemic stroke. In animal experiments, PB-006@MSC integrated reactive oxygen species (ROS) scavenging and neuroprotection. Thereby, it selectively targeted the cerebral ischemic penumbra (about fourfold higher accumulation at 24 h than in the non-targeted group), demonstrated a remarkable therapeutic efficacy in reducing the volume of cerebral infarction (from 37.1% to 2.3%), protected the neurogenic functions, and ameliorated the mortality.

Cancer cell membrane-camouflaged paclitaxel/PLGA nanoparticles for targeted therapy against lung cancer.

Paclitaxel (PTX) is a first-line drug for the treatment of lung cancer, but its targeting and therapeutic effect are unsatisfactory. Herein, lung cancer cell (A549) membrane biomimetic PTX-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (AM@PTX-NPs) were constructed to eliminate the shortcomings of PTX. The AM@PTX-NPs were successfully prepared with a high drug loading efficiency (10.90±0.06 %). Moreover, transmission electron microscopy, SDS-PAGE, and western blotting proved that AM@PTX-NPs were spherical nanoparticles camouflaged by the A549 cell membrane. Both in vitro and in vivo assays revealed that the AM@PTX-NPs displayed outstanding targeting capacity due to A549 membrane modification. The cytotoxicity experiment showed that the developed biomimetic formulation was able to effectively reduce the proliferation of A549 cells. Moreover, AM@PTX-NPs exhibited a significant tumor growth inhibition rate (73.00 %) with good safety in the tumor-bearing mice, which was higher than that of the PTX-NPs without A549 membrane coating (37.39 %). Overall, the constructed bioinspired vector could provide a novel platform for the PTX delivery and demonstrated a promising strategy for the targeted cancer treatment.

Engineered Leukocyte Biomimetic Colorimetric Sensor Enables High-Efficient Detection of Tumor Cells Based on Bioorthogonal Chemistry.

Accurate detection of heterogeneous circulating tumor cells (CTCs) is critical as they can make tumor cells more aggressive, drug-resistant, and metastasizing. Although the leukocyte membrane coating strategy is promising in meeting the challenge of detecting heterogeneous CTCs due to its inherent antiadhesive properties, it is still limited by the reduction or loss of expression of known markers. Bioorthogonal glycol-metabolic engineering is expected to break down this barrier by feeding the cells with sugar derivatives with a unique functional group to establish artificial targets on the surface of tumor cells. Herein, an engineered leukocyte biomimetic colorimetric sensor was accordingly fabricated for high-efficient detection of heterogeneous CTCs. Compared with conventional leukocyte membrane coating, the sensor could covalently bound to the heterogeneous CTCs models fed with Ac4ManNAz in vitro through the synergy of bioorthogonal chemistry and metabolic glycoengineering, ignoring the phenotypic changes of heterogeneous CTCs. Meanwhile, a sandwich structure composed of leukocyte biomimetic layer/CTCs/MoS2 nanosheet was formed for visual detection of HeLa cells as low as 10 cells mL-1. Overall, this approach can overcome the dependence of conventional cell membrane biomimetic technology on specific cell phenotypes and provide a new viewpoint to highly efficiently detect heterogeneous CTCs.

"Coir Raincoat"-Boosted Biomimetic Hydrogel for Efficient Solar Desalination and Wastewater Purification.

Solar-driven interfacial evaporation is an efficient method for purifying contaminated or saline water. Nonetheless, the suboptimal design of the structure and composition still necessitates a compromise between evaporation rate and service life. Therefore, achieving efficient production of clean water remains a key challenge. Here, a biomimetic dictyophora hydrogel based on loofah/carbonized sucrose@ZIF-8/polyvinyl alcohol is demonstrated, which can serve as an independent solar evaporator for clean water recovery. This special structural design achieves effective thermal positioning and minimal heat loss, while reducing the actual enthalpy of water evaporation. The evaporator achieves a pure water evaporation rate of 3.88 kg m-2 h-1 and a solar-vapor conversion efficiency of 97.16% under 1 sun irradiation. In comparison, the wastewater evaporation rate of the evaporator with ZIF-8 remains at 3.85 kg m-2 h-1 for 30 days, which is 16.3% higher than the light irradiation without ZIF-8. Equally important, the evaporator also showcases the capability to cleanse water from diverse sources of contaminants, including those with small molecules, oil, heavy metal ions, and bacteria, greatly improving the lifespan of the evaporator.

Nanofibrous Microspheres: A Biomimetic Platform for Bone Tissue Regeneration.

Bone, a fundamental constituent of the human body, is a vital scaffold for support, protection, and locomotion, underscoring its pivotal role in maintaining skeletal integrity and overall functionality. However, factors such as trauma, disease, or aging can compromise bone structure, necessitating effective strategies for regeneration. Traditional approaches often lack biomimetic environments conducive to efficient tissue repair. Nanofibrous microspheres (NFMS) present a promising biomimetic platform for bone regeneration by mimicking the native extracellular matrix architecture. Through optimized fabrication techniques and the incorporation of active biomolecular components, NFMS can precisely replicate the nanostructure and biochemical cues essential for osteogenesis promotion. Furthermore, NFMS exhibit versatile properties, including tunable morphology, mechanical strength, and controlled release kinetics, augmenting their suitability for tailored bone tissue engineering applications. NFMS enhance cell recruitment, attachment, and proliferation, while promoting osteogenic differentiation and mineralization, thereby accelerating bone healing. This review highlights the pivotal role of NFMS in bone tissue engineering, elucidating their design principles and key attributes. By examining recent preclinical applications, we assess their current clinical status and discuss critical considerations for potential clinical translation. This review offers crucial insights for researchers at the intersection of biomaterials and tissue engineering, highlighting developments in this expanding field.

Self-assembly of cascade nanoenzyme glucose oxidase encapsulated in copper benzenedicarboxylate for wearable sweat-glucose colorimetric sensors with smartphone readout.

BACKGROUND: With the advent of personalized medical approaches, precise and tailored treatments are expected to become widely accepted for the prevention and treatment of diabetes. Paper-based colorimetric sensors that function in combination with smartphones have been rapidly developed in recent years because it does not require additional equipment and is inexpensive and easy to perform. In this study, we developed a portable, low-cost, and wearable sweat-glucose detection device for in situ detection. RESULTS: The sensor adopted an integrated biomimetic nanoenzyme of glucose oxidase (GOx) encapsulated in copper 1, 4-benzenedicarboxylate (CuBDC) (GOx@CuBDC) through a biomimetic mineralization process. CuBDC exhibited a peroxide-like effect, cascade catalytic effect with the encapsulated GOx, and increased the enzyme stability. GOx@CuBDC and 3,3,5,5-tetramethylbenzidine were combined to form a hybrid membrane that achieved single-step paper-based glucose detection. SIGNIFICANCE AND NOVELTY: This GOx@CuBDC-based colorimetric glucose sensor was used to quantitatively analyze the sweat-glucose concentration with smartphone readings. The sensor exhibited a good linear relationship over the concentration range of 40-900 µM and a limit of detection of 20.7 µM (S/N = 3). Moreover, the sensor performed well in situ monitoring and in evaluating variations based on the consumption of foods with different glycemic indices. Therefore, the fabricated wearable sweat-glucose sensors exhibited optimal practical application performance.

Recent advances in biomimetic strategies for the immunotherapy of glioblastoma.

Immunotherapy is regarded as one of the most promising approaches for treating tumors, with a multitude of immunotherapeutic thoughts currently under consideration for the lethal glioblastoma (GBM). However, issues with immunotherapeutic agents, such as limited in vivo stability, poor blood-brain barrier (BBB) penetration, insufficient GBM targeting, and represented monotherapy, have hindered the success of immunotherapeutic interventions. Moreover, even with the aid of conventional drug delivery systems, outcomes remain suboptimal. Biomimetic strategies seek to overcome these formidable drug delivery challenges by emulating nature's intelligent structures and functions. Leveraging the variety of biological structures and functions, biomimetic drug delivery systems afford a versatile platform with enhanced biocompatibility for the co-delivery of diverse immunotherapeutic agents. Moreover, their inherent capacity to traverse the BBB and home in on GBM holds promise for augmenting the efficacy of GBM immunotherapy. Thus, this review begins by revisiting the various thoughts and agents on immunotherapy for GBM. Then, the barriers to successful GBM immunotherapy are analyzed, and the corresponding biomimetic strategies are explored from the perspective of function and structure. Finally, the clinical translation's current state and prospects of biomimetic strategy are addressed. This review aspires to provide fresh perspectives on the advancement of immunotherapy for GBM.

Biomimetic Metal-Organic Framework Gated Nanoplatform for Sonodynamic Therapy against Extensively Drug Resistant Bacterial Lung Infection.

Novel antimicrobial strategies are urgently needed to treat extensively drug-resistant (XDR) bacterial infections due to the high mortality rate and lack of effective therapeutic agents. Herein, nanoengineered human umbilical cord mesenchymal stem cells (hUC-MSCs), named PMZMU, are designed as a sonosensitizer for synergistic sonodynamic-nano-antimicrobial therapy against gram-negative XDR bacteria. PMZMU is composed of a bacterial targeting peptide (UBI29-41) modified hUC-MSCs membrane (MSCm), a sonosensitizer meso-tetra(4-car-boxyphenyl) porphine doped mesoporous organo-silica nanoparticle and an acidity-responsive metal-organic framework ZIF-8. This innovative formulation enables efficient loading of polymyxin B, reduces off-target drug release, increases circulation and targeting efficacy, and generates reactive oxygen species upon ultrasound irradiation. PMZMU exhibits remarkable in vitro inhibitory activity against four XDR bacteria: Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa (PA), and Escherichia coli. Taking advantage of the bacterial targeting ability of UBI29-41 and the inflammatory chemotaxis of hUC-MSC, PMZMU can be precisely delivered to lung infection sites thereby augmenting polymyxin B concentration. PMZMU-mediated sonodynamic therapy significantly reduces bacterial burden, relieves inflammatory damage by promoting the polarization of macrophages toward M2 phenotype, and improves survival rates without introducing adverse events. Overall, this study offers promising strategies for treating deep-tissue XDR bacterial infections, and guides the design and optimization of biomimetic nanomedicine.

Biomimetic Mechanical Robust Cement-Resin Composites with Machine Learning-Assisted Gradient Hierarchical Structures.

Biological materials relying on hierarchically ordered architectures inspire the emergence of advanced composites with mutually exclusive mechanical properties, but the efficient topology optimization and large-scale manufacturing remain challenging. Herein, this work proposes a scalable bottom-up approach to fabricate a novel nacre-like cement-resin composite with gradient brick-and-mortar (BM) structure, and demonstrates a machine learning-assisted method to optimize the gradient structure. The fabricated gradient composite exhibits an extraordinary combination of high flexural strength, toughness, and impact resistance. Particularly, the toughness and impact resistance of such composite attractively surpass the cement counterparts by factors of approximately 700 and 600 times, and even outperform natural rocks, fiber-reinforced cement-based materials and even some alloys. The strengthening and toughening mechanisms are clarified as the regional-matrix densifying and crack-tip shielding effects caused by the gradient BM structure. The developed gradient composite not only endows a promising structural material for protective applications in harsh scenarios, but also paves a new way for biomimetic metamaterials designing.

Double Imprinted Nanoparticles for Sequential Membrane-to-Nuclear Drug Delivery.

Efficient and site-specific delivery of therapeutics drugs remains a critical challenge in cancer treatment. Traditional drug nanocarriers such as antibody-drug conjugates are not generally accessible due to their high cost and can lead to serious side effects including life-threatening allergic reactions. Here, these problems are overcome via the engineering of supramolecular agents that are manufactured with an innovative double imprinting approach. The developed molecularly imprinted nanoparticles (nanoMIPs) are targeted toward a linear epitope of estrogen receptor alfa (ERα) and loaded with the chemotherapeutic drug doxorubicin. These nanoMIPs are cost-effective and rival the affinity of commercial antibodies for ERα. Upon specific binding of the materials to ERα, which is overexpressed in most breast cancers (BCs), nuclear drug delivery is achieved via receptor-mediated endocytosis. Consequentially, significantly enhanced cytotoxicity is elicited in BC cell lines overexpressing ERα, paving the way for precision treatment of BC. Proof-of-concept for the clinical use of the nanoMIPs is provided by evaluating their drug efficacy in sophisticated three-dimensional (3D) cancer models, which capture the complexity of the tumor microenvironment in vivo without requiring animal models. Thus, these findings highlight the potential of nanoMIPs as a promising class of novel drug compounds for use in cancer treatment.

Multifunctional Biomimetic Nanocarriers for Dual-Targeted Immuno-Gene Therapy Against Hepatocellular Carcinoma.

Growing evidences have proved that tumors evade recognition and attack by the immune system through immune escape mechanisms, and PDL1/Pbrm1 genes have a strong correlation with poor response or resistance to immune checkpoint blockade (ICB) therapy. Herein, a multifunctional biomimetic nanocarrier (siRNA-CaP@PD1-NVs) is developed, which can not only enhance the cytotoxic activity of immune cells by blocking PD1/PDL1 axis, but also reduce tumor immune escape via Pbrm1/PDL1 gene silencing, leading to a significant improvement in tumor immunosuppressive microenvironment. Consequently, the nanocarrier promotes DC cell maturation, enhances the infiltration and activity of CD8+ T cells, and forms long-term immune memory, which can effectively inhibit tumor growth or even eliminate tumors, and prevent tumor recurrence and metastasis. Overall, this study presents a powerful strategy for co-delivery of siRNA drugs, immune adjuvant, and immune checkpoint inhibitors, and holds great promise for improving the effectiveness and safety of current immunotherapy regimens.

A biomimetic spore nanoplatform for boosting chemodynamic therapy and bacteria-mediated antitumor immunity for synergistic cancer treatment.

Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer. However, the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations. Furthermore, monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors. In this study, based on our discovery that spore shell (SS) of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity, we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy, chemodynamic therapy and antitumor immunity for synergistic cancer treatment. In detail, SS is separated from probiotic spores and then attached to the surface of liposome (Lipo) that was loaded with hemoglobin (Hb), glucose oxidase (GOx) and JQ1 to construct SS@Lipo/Hb/GOx/JQ1. In tumor tissue, highly toxic hydroxyl radicals (•OH) are generated via sequential catalytic reactions: GOx catalyzing glucose into H2O2 and Fe2+ in Hb decomposing H2O2 into •OH. The combination of •OH and SS adjuvant can improve tumor immunogenicity and activate immune system. Meanwhile, JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response. In this manner, SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis. To summarize, the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.