Tessellation-based polyhedral microstructures derived from Voronoi and Laguerre constructions provide a realistic geometric foundation for modeling bioinspired organic-inorganic composites with interfacial fracture. However, even after extensive centroidal relaxation, such tessellations retain numerous lower-dimensional geometric degeneracies-very short edges and small or sliver-like faces-that severely hinder volumetric meshing and render large-scale cohesive-zone simulations computationally impractical. In this work, we employ a geometric regularization step that enforces a minimum admissible feature length prior to meshing and systematically quantify its impact on downstream performance in finite element discretization and cohesive fracture simulation. By eliminating geometric features below the prescribed length scale while preserving grain topology and morphology, the regularized tessellations exhibit sharply improved edge-length and face-diameter distributions and become readily meshable at practical resolutions. When applied to a 3D bioinspired organic-inorganic composite with cohesive interfaces, the regularized geometry reduces volumetric and cohesive element counts nearly fivefold and increases the explicit stable time increment by approximately four orders of magnitude, transforming an otherwise diverging analysis into a robust simulation that converges to the prescribed deformation. These results demonstrate that the prescribed geometric regularization step is not merely a preprocessing refinement but a critical enabling step for efficient and large-scale cohesive fracture simulations of tessellation-based bioinspired composites.

Periodontitis is a chronic disease characterized by periodontal tissue inflammation and alveolar bone resorption, in which regulating the immune microenvironment and controlling inflammation are primary therapeutic goals. However, current approaches are limited by the need for high systemic doses, insufficient local drug concentration, and short retention time. Herein, we developed a miRNA-126 nanoparticles@doxycycline dissolving microneedle patch (miR-126 NPs@DOX MN) for localized codelivery of miRNA-126 nanoparticles (miR-126 NPs) and doxycycline (DOX) to gingival tissue, aiming to achieve anti-inflammation and periodontal tissue regeneration. The MN possesses sufficient mechanical strength for gingival tissue penetration, resists salivary washout, and enables localized codelivery of miR-126 NPs and DOX, prolonging their retention within periodontal tissue. Moreover, the miR-126 NPs@DOX MN protects miRNA-126 from enzymatic degradation in the complex oral environment, preserving its bioactivity. Mechanistically, miRNA-126 and DOX, respectively, modulate the reactive oxygen species/NF-κB signaling pathway, thereby remodeling the immune microenvironment and alleviating inflammation. In vivo experiments further confirmed that the miR-126 NPs@DOX MN modulated macrophage polarization, not only reducing inflammation but also promoting alveolar bone regeneration. Collectively, the miR-126 NPs@DOX MN demonstrates potential as a localized therapeutic strategy for anti-inflammatory and immunomodulatory treatment of periodontitis.

Microneedles (MNs) represent a rapidly evolving transdermal drug delivery method, with ongoing development effort s f ocused on overcoming challenges such as limited drug loading and pore occlusion. Herein, we report dissolvable MNs vaccine with excellent drug loading as well as other positive features that make it an ideal delivery carrier in tumor immunotherapy. This study employs a biodegradable polydopamine-based nano-delivery system to co-encapsulate both Toll-like receptor 7/8 agonist resiquimod (R848) and ovalbumin (OVA) antigens, which are subsequently incorporated into MN patches to achieve synergistic photothermal-immunotherapeutic effects. The MN vaccine targets tumor sites via transdermal administration, exhibiting significant therapeutic efficacy by enabling deep tissue drug release and maintaining prolonged therapeutic levels for at least 3 days. The MN tips are rapidly degraded under photothermal action to release R848 and OVA, can effectively polarizes the tumor-associated macrophages to M1-type macrophages and activate dendritic cells to enhance immune response in vivo , thereby, the MN vaccines have shown excellent efficacy and good safety, resulting in a sufficient and persistent anti-tumor cellular immune response with potent tumor immunotherapeutic efficacy. In brief, this study demonstrates that MN administration successfully delivers polydopamine-based nanotherapeutics to tumor sites and validates their anti-tumor efficacy. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Immunogenic cell death (ICD) provides a promising strategy for cancer treatment by stimulating anti-tumor immunity. However, single ICD inducers often elicit insufficient damage-associated molecular patterns (DAMPs), and the rapid clearance of these DAMPs at the tumor site further prevents sustained immune stimulation. To address these challenges, we developed a polyphenol-based bioadhesive hydrogel antigen reservoir functionalized with dopamine (DA) and loaded with dual ICD inducers. Specifically, thymidine kinase (tk)-deficient oncolytic vaccinia virus (VV, a type II ICD inducer) was combined with oxaliplatin (OXA, a type I ICD inducer), thereby enhancing direct tumor cytotoxicity and synergistically amplifying ICD through distinct mechanisms to promote robust DAMP release. Subsequently, the released DAMPs were captured and retained by the DA-functionalized hyaluronic acid-Pluronic® F127 hydrogel (HADP), forming an antigen reservoir at the tumor site. This synergistic “stimulate-and-retain” strategy not only augments ICD-mediated DAMP release but also prolongs their local availability to sustain immune stimulation. In murine models, the OXA-HADP@VV facilitated dendritic cell (DC) activation, increased IFN-γ+CD8+ T cell infiltration, and reduced regulatory T cells (Tregs), thereby achieving effective tumor suppression and strong anti-recurrence effects. Together, this dual ICD-inducing antigen reservoir provides a versatile platform for improving cancer immunotherapy.

Tessellation-based polyhedral models derived from Voronoi and Laguerre diagrams provide a natural geometric framework for modeling bioinspired organic-inorganic composites and polycrystalline materials. However, such tessellations inherently contain lower-dimensional geometric degeneracies-including near-zero-length edges and sliver-like faces-that persist even after extensive centroidal relaxation and severely limit robust volumetric meshing and large-scale finite element (FE) simulations. This work presents a dedicated regularization framework that enforces a prescribed minimum feature size directly on polyhedral tessellations while preserving grain topology, morphology, and statistical size distributions. The approach systematically eliminates problematic geometric features through topology-safe collapse operations guided by adaptive quality control, without resorting to global remeshing. Applications to representative three-dimensional microstructures demonstrate sharp truncation of the lower tails of edge-and face-size distributions and substantial improvements in polyhedral shape quality. When used as a preprocessing step, the regularized geometries enable stable and computationally efficient FE simulations with cohesive interfaces, reducing element counts by more than an order of magnitude and increasing explicit stable time increments by several orders of magnitude. The proposed framework, therefore, provides an essential geometric conditioning step for practical, large-scale computational modeling of bioinspired composites and tessellation-based polycrystalline systems. The implementation of the regularizer program is available as an open-source project on GitHub at https://github.com/Rumi381/regularizer.git.

Surface functional modification on magnetic nanoparticles (MNPs) has attracted considerable interest in the biomedical field because of their special characteristics, such as high specific surface area, tunable structure, excellent biosafety and convenient magnetic separation. Herein, surface functionalization strategies of MNPs and their application in biomedicine have been summarized and discussed. Surface chemical functionalization methods, including the surface coating of ligands, organic polymers, inorganic silica material, and noble metals are discussed, which contribute to better biological activity and functional performance. For biomedical applications, advanced developments have been highlighted, including biomedical imaging, targeted drug delivery, theragnostic, recognition and capture of bacteria, inhibiting the growth of microbes, and detoxification treatment by catalysis. Different treatment methods, including magnetic imaging, magnetic separation, photothermal and photocatalytic processes, and reactive oxygen species production, perspectives on the direction of research on MNPs for biomedical application are presented. Finally, the challenges and prospects of multifunctional MNPs for biomedical applications in the future are discussed.

Gout is a chronic inflammatory arthritis caused by the deposition of monosodium urate (MSU) crystals in joints and other areas, and the MSU crystals is a result of the progressive long-term hyperuricemia. Therefore, long-term gout management requires a combination of on-demand urate lowering therapy and anti-inflammatory treatment. And the long-term combined administration urgently requires a simplified and effective administration method. Here, we developed a smart hydrogel microneedle system featuring urate-responsive drug release and rapid bubble separation. This system utilized the rapid bubble separation to retain the hydrogel drug reservoir that simultaneously carried the urate lowering drug uricase and the anti-inflammatory drug colchicine in the skin. In hyperuricemia, the ROS-responsive hydrogel formed by the spontaneous cross-linking of dopamine-modified β-cyclodextrin, polyvinyl alcohol and phenylboric acid linker was promoted for degradation by the H2O2 released from the decomposition of uric acid by uricase, thereby achieving the urate-responsive release. In addition, colchicine loading was increased by forming inclusion complexes with dopamine-modified β-cyclodextrin. Thus, this smart microneedle system retained the drug reservoir with urate-responsive release in the skin through transdermal delivery. It not only dynamically controlled the uric acid concentration and decomposed MSU crystals, but also has a powerful real-time anti-inflammatory effect on gout flares. Accordingly, we believe the smart microneedle system has great potential for long-term gout management.

PROteolysis TArgeting Chimeras (PROTACs) have gained significant attention for targeted protein degradation in cancer therapy. However, their clinical application is limited by low bioavailability, poor tumor distribution, and potential off-target effects. This study presents NaC4A-PROTACs, a hypoxia-responsive host-guest drug delivery system where azo-modified calixarene derivative (Naph-SAC4A) acts as the host molecule, encapsulating PROTAC molecules as the guest. The PROTAC molecules are incorporated into the host cavity of Naph-SAC4A through reversible non-covalent interactions, forming well-defined supramolecular complexes, which, to our knowledge, represent the first supramolecular host-guest PROTAC delivery system. These complexes remain stable under normoxic physiological conditions. But in the hypoxic tumor microenvironment, Naph-SAC4A undergo enzyme-catalyzed azo bond cleavage, significantly reducing the host-guest binding affinity of the supramolecular complex. Subsequently, PROTAC molecules are efficiently released from the calixarene cavity to degrade bromodomain-containing protein 4 (BRD4) proteins. We demonstrate the efficacy of NaC4A-PROTACs for hypoxia-targeted therapy both in vitro and in vivo, showing significant enhancement of PROTACs bioavailability, improved tumor-specific delivery, and potent anti-tumor effects. Our study provides a simple, universal, and reproducible platform for the controlled release of PROTACs, which can effectively enhance the precision and efficacy of cancer therapy, providing a promising approach for the application of PROTACs in cancer treatment.

One of the enduring goals in structural materials engineering is the development of lightweight materials that combine high strength with exceptional toughness. Natural composites such as nacre have long served as a source of inspiration, as their outstanding mechanical performance stems not only from their intricate hierarchical architecture but also from the vital role of interfaces in controlling deformation and resisting crack propagation. Here, we present a computational model of a three-dimensional (3D) staggered nacre-mimicking nanocomposite and report parametric studies that investigate the roles of interfacial properties (strength and toughness) in controling the bulk properties and failure behaviors under both tensile and compressive loading conditions. Our findings reveal that under tensile loading, the bulk properties are primarily controlled by the surface normal interfacial properties, and composite failure exhibits normal-mode fracture patterns. In contrast, under compressive loading, interfacial shear properties predominantly control the bulk properties, and composite failure patterns follow shear-mode fracture behavior. These findings provide specific design guidelines for tailoring the interfacial properties of nacre-like bioinspired structural composites under different loading conditions.

The treatment of chronic wounds still presents great challenges due to being infected by biofilms and the damaged healing process. The current treatments do not address the needs of chronic wounds. In this study, a highly effective dressing (Dox-DFO@MN Hy) for the treatment of chronic wounds is described. This dressing combines the advantages of microneedles (MNs) and hydrogels in the treatment of chronic wounds. MNs is employed to debride the biofilms and break down the wound barrier, providing rapid access to therapeutic drugs from hydrogel backing layer. Importantly, to kill the pathogenic bacteria in the biofilms specifically, Doxycycline hydrochloride (Dox) is wrapped into the polycaprolactone (PCL) microspheres that have lipase-responsive properties and loaded into the tips of MNs. At the same time, hydrogel backing layer is used to seal the wound and accelerate wound healing. Benefiting from the combination of two advantages of MNs and hydrogel, the dressing significantly reduces the bacteria in the biofilms and effectively promotes angiogenesis and cell migration in vitro. Overall, Dox-DFO@MN Hy can effectively treat chronic wounds infected with biofilms, providing a new idea for the treatment of chronic wounds.

Glucose, a primary energy source derived from animals’ feed ration, is crucial for their growth, production performance, and health. However, challenges such as metabolic stress, oxidative stress, inflammation, and gut microbiota disruption during animal production practices can potentially impair animal glucose metabolism pathways. Phytochemicals, probiotics, prebiotics, and trace minerals are known to change the molecular pathway of insulin-dependent glucose metabolism and improve glucose uptake in rodent and cell models. These compounds, commonly used as animal feed additives, have been well studied for their ability to promote various aspects of growth and health. However, their specific effects on glucose uptake modulation have not been thoroughly explored. This article focuses on glucose metabolism is on discovering alternative non-pharmacological treatments for diabetes in humans, which could have significant implications for developing feed additives that enhance animal performance by promoting insulin-dependent glucose metabolism. This article also aims to provide information about natural materials that impact glucose uptake and to explore their potential use as non-antibiotic feed additives to promote animal health and production. Further exploration of this topic and the materials involved could provide a basis for new product development and innovation in animal nutrition.

Despite targeted therapies like epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), non-small cell lung cancer (NSCLC) remains a clinical challenge due to drug resistance hampering their efficacy. Here, we designed an "AND" logic gate-based supramolecular therapeutic platform (HA-BPY-GEF-NPs) for the treatment of EGFR-TKI resistant NSCLC. This system integrates both internal and external stimuli-responsive mechanisms that need to be activated in a preset sequence, enabling it to precisely control drug release behavior for enhancing therapeutic precision. By programming the system to respond to sequential near-infrared (NIR) irradiation and enzyme (cathepsin B) inputs, the release of gefitinib is effectively confined to the tumor region. Moreover, the NIR irradiation induces reactive oxygen species production, suppressing tumor growth and inhibiting bypass signaling pathways. The designed drug delivery system offers a highly controlled and targeted therapeutic approach, effectively inhibiting tumor growth, suppressing bypass signaling pathways, and overcoming EGFR-TKI resistance, thus offering a potential solution for maximizing therapeutic benefits.

Due to the limitations of conventional chemotherapy including side effects, poor prognosis, and drug resistance, there is an urgent need for the development of a novel multi-functional combined therapy strategy. Dopamine-modified oxaliplatin prodrug (OXA-DA) was successfully synthesized in this study to ameliorate the organ distribution of oxaliplatin for improving the drug efficacy and reducing toxic side effects, and OXA-DA was applied to develop a porous oxaliplatin cross-linked polydopamine nanoparticle for loading siPD-L1 to construct multifunctional nanoplatform. The multifunctional nanoplatform was modified with poly(2-ethyl-2-oxazoline) (PEOz), which occurred charge reversal in the tumor microenvironment, and exerted the lysosomal escape effect in tumor cells to improve the bioavailability of small interfering RNA targeting programmed cell death-ligand 1 (siPD-L1). The pH-responsive charge reversal, photothermal, biodegradation, lysosomal escape ability, PD-L1 protein degradation, toxicity properties and multiple antitumor effects were comprehensively evaluated in vitro and in vivo experiments. The findings indicated that OXA-DA-siPD-L1@PDA-PEOz excellently induced tumor cell necrosis and apoptosis as a result of the synergistic effect of chemo-photothermal therapy, and upregulated CD8+ T cells produced interferon-γ (IFN-γ) to further attack the tumor cells. In conclusion, the novel nanoplatform-mediated chemo/photothermal/immunotherapy has promising clinical applications in the treatment of malignant tumors.

The challenges of multi-pathway immune resistance and systemic toxicity caused by the direct injection of immune checkpoint inhibitors are critical factors that compromise the effectiveness of clinical immune checkpoint blockade therapy. In this context, natural polyphenols have been employed as the primary component to construct a targeted and acid-responsive PD-L1 antibody (αPD-L1) delivery nanoplatform. This platform incorporates garcinol, an inhibitor of the Nuclear Factor Kappa-B (NF-κB) signaling pathway, to regulate pro-tumor immune escape cytokines and regulatory T cells. Additionally, the nanoplatform has been verified to induce immunogenic cell death (ICD), which promotes the maturation of dendritic cells and enhances the activity of cytotoxic T lymphocytes. In vivo and in vitro experimental results demonstrated that the nanoplatform can boost the immune response through a PD-L1 and NF-κB blocking/ICD inducing three-pronged strategy, thereby effectively combating tumor growth and metastasis.

Microneedle array systems loaded with responsive nanoparticles have received increasing attention due to the advantages of good drug stability, targeting ability, controlled release of drugs, high bioavailability, painlessness, and good patient compliance. Compared with oral drug delivery, microneedle transdermal drug delivery eliminates the need to pass through the gastrointestinal tract and liver, reducing the metabolic consumption of drugs by first‐pass effect. While compared with intravenous drug delivery, microneedle transdermal drug delivery reduces patient discomfort and does not require professional administration. However, there are few review articles on microneedles loaded with responsive nanoparticles. Herein, the current researches on microneedles loaded with specific responsive nanoparticles such as glucose‐responsive, pH‐responsive, enzyme‐responsive, light‐responsive, magnetic‐responsive, ultrasound‐responsive, and multiresponsive, and the biomedical application of these microneedle array systems are summarized. In addition, the challenges and prospects of microneedle strategies loaded with responsive nanoparticles are briefly discussed, which will facilitate the development of such versatile drug‐delivery strategy.

Cordyceps sinensis is a valuable Chinese medicine, possessing multiple bioactive compounds with diverse pharmacological effects. The extracts of C. sinensis, especially the polysaccharide fraction, can suppress the proliferation of different tumor cells, induce apoptosis, and stimulate antitumor immune responses. However, C. sinensis polysaccharides (CSP) have yet to be characterized, with a rare reporting of their effective doses. Immunotherapy depends on harnessing the inherent ability of the immune system to recognize and eliminate tumor cells. Polarizing the anti-inflammatory M2 tumor-associated macrophages (TAMs) to the pro-inflammatory M1 phenotype is an effective antitumor immunotherapy strategy. We designed a drug delivery system with black phosphorus (BP) nanosheets loaded with CSP for synergistic antitumor photothermal therapy (PTT) and immunotherapy. The BP/CSP@PDA-PEG-FA nanoparticles (NPs) enhanced the polarization of M2 macrophages to the M1 phenotype in vitro and in vivo. Moreover, the NPs inhibited the growth of 4T1 xenografts upon near-infrared (NIR) laser stimulation by causing photothermal ablation of tumor cells and promoting T cell-mediated antitumor immune responses. Therefore, BP/CSP@PDA-PEG-FA NPs are a promising platform for combined PTT and immunotherapy for breast tumors.

The therapeutic application of STING agonists in various malignancies has been limited by factors such as the inability of systemic administration and the immunosuppressive tumor microenvironment. Herein, this work reports a mesoporous polydopamine‐based multifunctional nanoplatform loaded with STING agonist MSA‐2 and chelated with Mn 2+ for synergistic photothermal and STING activation‐based immunotherapy. The nanoplatform effectively delivers MSA‐2 to the tumor site and intelligently releases its contents through acid degradation, facilitated by the photothermal effect. Additionally, the thermal ablation of tumor tissue can induce immunogenic cell death, which helps alleviate the immunosuppressive tumor microenvironment, thereby enhancing the efficacy of MSA‐2. Furthermore, Mn 2+ works as a dual‐acting STING sensitizer and MRI contrast agent which not only boosts the immune response but also allows real‐time MRI tracking of the nanoplatform. This strategy is proved highly efficacious both in impeding primary/metastatic tumor and in eliciting a robust tumor‐specific immune response. Collectively, an effective multifunctional nanoplatform for the systemic delivery of STING agonist which synergized photothermal therapy and STING pathway activation‐mediated immunotherapy is highlighted here to provide new ideas and strategies for optimizing combination therapy for cancer treatment.

Insufficient immune stimulation and stubborn immune resistance are the critical factors limiting tumor immunotherapy. Here, we report a multifunctional nanoprodrug platform with self-driven indoximod (IND) release and oxidative stress amplification. The aim is to awaken immune responses and block the indoleamine 2,3-dioxygenase (IDO) pathway through a combination of ferroptosis, photothermal therapy, and immunotherapy. This nanosystem improved the delivery efficiency of IND due to click chemistry linked ROS responsive prodrug and self-driven drug release. Meanwhile, the tactic of simultaneously increasing ROS and eliminating GSH amplified oxidative stress and strengthened ferroptosis, which further enhanced immunogenicity along with polydopamine-based photothermal therapy. IDO immunization combined with ferroptosis as well as photothermal therapy not only stimulated immune response, but also reversed immune suppression with enhanced immune memory. Therefore, primary tumor, distant tumor, and cancer metastasis were inhibited. This study provides a perspective on immunotherapeutics for cancer treatment.

Natural polysaccharides, represented by dextran, chitosan, and hyaluronic acid, are widely approved for use as pharmaceutical excipients and are important carrier materials for the design of advanced drug delivery systems, particularly in the field of anticancer drug delivery. The combination of stimuli-activable prodrug based chemotherapy and photodynamic therapy (PDT) has attracted increasing attention. Recent studies have verified the effectiveness of this strategy in the treatment of multiple aggressive cancers. However, in such combination, the stimuli-responsive chemotherapy and PDT have their own problems that need to be overcome. The uneven distribution of endogenous stimuli within tumor tissues makes it difficult for prodrug to be completely activated. And the inadequate tissue penetration depth of external light results in low efficiency of PDT. Aiming at these two bottlenecks, we designed a biocompatible dextran based - multi-component nanomedicine (PCL-NPs) that integrate a chemiluminescence agent luminol, a photosensitizer chlorine e6 (Ce6), and a reactive oxygen species (ROS)-activable thioketal-based paclitaxel (PTX) prodrug. The presence of overexpressed hydrogen peroxide (H2O2) inside tumor oxidizes the luminol moiety to generate in-situ light for PDT through chemiluminescence resonance energy transfer (CRET). The singlet oxygen (1O2) produced in this process not only directly kills tumor cells but also amplifies oxidative stress to accelerate the activation of PTX prodrug. We propose that the PCL-NPs have great therapeutic potential by simultaneously enhancing chemotherapy and PDT in a combination therapy.

Seasonal influenza A viruses continue to pose a public health threat, and current vaccines are not sufficiently effective because of virus mutation. There is an urgent need to develop a broad-protection influenza A vaccine. Our team previously designed potential universal hemagglutinin (HA) sequences against seasonal influenza A H1N1 and H3N2 (mH1 and mH3, respectively) through a mosaic strategy. In this study, we construct DNA vaccines by linking the antigens mH1 and mH3 via internal ribosome entry sites and then wrap the DNA with the deoxycholic acid-modified polyetherimide to form DNA nanovaccines. A microneedle is used to deliver DNA nanovaccines, and the data show that better cellular and cross-reactivity and protective immunity are induced compared with the intramuscular injection method. These results suggest that microneedle-based delivery of DNA nanovaccines could be a promising platform for development of a broad-protection influenza vaccine.