Ferroptosis has been widely explored as a promising cancer therapeutic target. Conventional ferroptosis induction relies on inhibiting glutathione peroxidase 4 (GPX4) to promote lipid peroxide accumulation. However, its efficacy is often limited by insufficient endogenous unsaturated lipids in tumor cells. To address this limitation, we developed a lipid-prodrug nanoamplifier (SIM-SS-LA NAs), composed of disulfide-linked linoleic alcohol and simvastatin (SIM) to enhance ferroptosis. Significant, the modularity of the prodrug not only promotes the assembly of the SIM but also amplifies its ferroptosis effect. In the highly reductive tumor microenvironment, disulfide bonds are cleaved, releasing SIM and LA. Notably, the released LA acts as an exogenous substrate, substantially increasing lipid peroxide accumulation and synergizing with SIM-mediated GPX4 inhibition to amplify ferroptosis. As expected, the lipid-prodrug nanoamplifier showed potent ferroptosis-driven antitumor activity in a 4T1 breast tumor-bearing mouse model, offering an efficient nanotherapeutic strategy for ferroptosis-based cancer therapy.

Effective treatments for metabolic syndrome remain limited by challenges including systemic side effects and inefficient dietary intervention strategies. Here, we engineered 3-nitrophenylboronic acid-functionalized mesoporous silica nanoparticles (MSN-PBA(4)) designed for gut-restricted action, with particle size (similar to 240 nm) to decrease absorption and systemic exposure. The nanoparticles demonstrated robust ability to sequester dietary carbohydrates and fats via boronate ester formation with cis-diol groups, and simultaneously inhibited digestive enzymes (alpha-glucosidase, alpha-amylase, and lipase) through non-specific binding interactions. Intragastric administration of MSN-PBA(4) significantly reduced postprandial glucose and lipid absorption in mouse models of obesity and diabetes, and notably reversed metabolic dysfunctions in long-term feeding studies without systemic toxicity. This gut-localized dual-action nanoparticle system represents a promising therapeutic strategy with potential clinical translation for safe and effective management of metabolic diseases.

Starvation therapy (ST), which aims to hinder the rapid proliferation of cancer cells by depriving oxygen and nutrients, has been considered an ideal approach for cancer treatment. However, the limitations of traditional ST schemes, such as low targeting efficacy, undesired systemic side effects, elevated tumor hypoxia, induced drug resistance, and increased tumor metastasis risk, limit clinical applications. To overcome these challenges, numerous nanomedicines have been engineered in recent years to advance ST-driven antitumor therapy. Against this backdrop, there is an urgent need to summarize the latest advances in advanced nanomaterial-enabled cancer starvation therapy. Herein, we aim to highlight the emerging breakthroughs at the intersection of ST, nanotechnology, and cancer treatment in this rapidly evolving field. This review focuses on several ST-related inducible strategies, including nutrient supply regulation, key nutrient deprivation, and some emerging approaches. Furthermore, it highlights the synergistic benefits of combining ST with other therapeutic modalities, including phototherapy, chemodynamic therapy, chemotherapy, ferroptosis, gas therapy, and immune therapy. Finally, the existing challenges and future perspectives on the clinical ST of tumors are discussed.

Albumin-based nanoparticle (ANP) drug delivery systems have achieved significant clinical success. However, the low affinity between Doxorubicin (DOX) and human serum albumin (HSA) hinders the formation of stable nanoparticles. In our studies, we initially conjugated DOX to disulfide bond-containing fatty alcohols via carboxamide bond to systematically evaluate the impact of carbon chain length (C4, C8, C12, C20) on the binding affinity between DOX and HSA. Notably, when the carbon chain length of fatty alcohols reached eight (C8), DOX exhibited strong binding affinity to HSA. However, these prodrugs exhibited weak cytotoxicity, indicating insufficient DOX release due to the stable carboxamide bond. To address this issue, we further replaced the stable carboxamide bond with relative active carbamate bond (DOX-OCO-C8). Under high glutathione (GSH) conditions in tumor cells, DOX-OCO-C8 ANPs exhibited accelerated hydrolytic activity and efficient release of DOX. The ANPs significantly improved the pharmacokinetic profile and antitumor efficacy of DOX while reducing systemic toxicity. Our findings suggested optimizing alkyl chain lengths and linker chemistry offers a promising strategy for developing effective and safe DOX prodrug ANPs.

Small-molecule prodrug nanoassemblies (SMP-NAs) represent a promising nanomedicine for cancer therapy, enabling carrier-free characteristics and facile fabrication. However, the development of SMP-NAs currently relies on empirical trial-and-error screening, as quantitative descriptors to predict the relationship between molecular structure and self-assembly remain unavailable. Here, we introduce chemical topology indices, traditionally restricted to small-molecule drug discovery, as predictive tools for the rational design of SMP-NAs. We synthesized three topological SN38 prodrugs with distinct topological architectures (linear, cyclic and branched) but identical lipophilicity. Topological indices quantitatively capture the critical molecular characteristics of the prodrugs. Notably, the branched architecture (SN38-Br) provides molecular flexibility for efficient core packing while maintaining sufficient steric hindrance to prevent over-aggregation. Consequently, SN38-Br NPs exhibited superior colloidal stability, systemic blood circulation, robust tumor accumulation and antitumor activity. Our work establishes a theoretical framework for the quantitative structure-activity relationship (QSAR) of SMP-NAs, offering a blueprint for the transition from empirical screening to Nano-QSAR.

Self-assembled prodrug nanoassemblies integrate drug, response, and modification modules. Incorporating modification modules offers a strategy to balance efficacy-toxicity in cancer nanomedicine, yet how topology governs their structure-function relationship remains elusive. Here, we report a topological prodrug nanoassembly platform by conjugating docetaxel with fatty acid-based modification modules with linear, branched, or cyclic structure. This platform provides the systematic evidence that (i) topology dictates assembly mechanisms by modulating hydrophobic interactions and local energetic environments, as revealed through quantum chemical and multiscale analyses; and (ii) topology regulates bioactivity and toxicity in vitro/vivo, revealing a clear relationship of efficacy and safety. Nanoassemblies with linear modules excelled in key functional metrics, including assembly kinetics, release, and antitumor efficacy. Cyclic nanoassemblies maximized safety despite reduced potency, and branched nanoassemblies showed intermediate performance. By encoding performance into molecular topology, this work advances a key design parameter for prodrug-based cancer nanotherapeutics.

Overcoming the penetration barrier of nanomedicines remains a paramount challenge in antitumor therapy. Apoptotic bodies (ApoBDs), which are naturally generated from apoptotic cells, can mediate a potent neighboring effect by transferring drug to neighboring tumor cells via macropinocytosis. To amplify this process, we developed a tumor microenvironment-responsive nanoplatform (named as AD-NVs@CPP) to selectively enhance chemokine (C-X-C motif) receptor 4 (CXCR4) receptor-stimulated macropinocytosis. This platform was constructed by co-encapsulating doxorubicin (DOX) and the hypoxia-activated pro-drug AQ4N into homologous tumor cell membrane-derived nanovesicles (AD-NVs), followed by biomineralization of a calcium phosphate (CaP) shell that incorporated a CXCR4-targeting peptide (RFFE-SHAPAKPVSLSYR). The resultant AD-NVs@CPP exhibited a core-shell structure with a hydrodynamic diameter of similar to 180 nm and achieved a high peptide encapsulation efficiency of 81.6 % +/- 8.2 %. The CaP shell demonstrated excellent pH-responsive dissolution, releasing similar to 50 % of the peptide within 24 h at pH 6.5 ( vs. negligible release at pH 7.4), which consequently promoted cellular uptake and enhanced cytotoxicity under acidic conditions in vitro . Additionally, AD-NVs@CPP-induced ApoBDs served as efficient drug reservoirs, delivering drugs to adjacent cells with an IC50 value of 0.98 mu g/mL (in terms of protein concentration). In vivo , AD-NVs@CPP significantly prolonged the blood circulation time (increasing the halflife of DOX compared to the free drug solution) and improved tumor accumulation. Crucially, it enabled programmed drug penetration: AQ4N was selectively delivered into deep hypoxic tumor regions, mediating comprehensive tumor growth inhibition while maintaining a favorable safety profile. This work provides a robust strategy for achieving deep tumor penetration through the synergistic enhancement of macropinocytosis and the ApoBD-mediated neighboring effect. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Choroidoretinopathy is a major public health concern that causes significant vision impairment. Although therapeutic antibodies have demonstrated potential in treating these conditions, intravitreal injections remain invasive, associated with adverse effects, and require repeated traumatic administrations. Non-invasive drug delivery methods, such as eye drops, represent an ideal alternative but are limited by ocular barriers, making it difficult for drugs to effectively reach specific lesions. In this study, we introduce a novel reactive oxygen species (ROS)-responsive transmembrane peptide-antibody conjugate (PAC) designed for non-invasive, precise antibody delivery to the deep fundus region. The responsive PAC, termed trans-activator of transcription-polyethylene glycol-maleimide (TAT-MPEG)-antibody, is synthesized by linking transmembrane peptides TAT to maleimide via ROS-sensitive diselenide bonds, enabling efficient antibody conjugation. Following eye drop administration, TAT enhances ocular penetration, allowing the conjugate to traverse ocular barriers and deliver antibodies directly to the posterior segment. Moreover, the diselenide bonds facilitate antibody release in oxidative environments, ensuring targeted drug localization at disease sites. In mouse models of choroidal neovascularization and choroidal melanoma, this conjugate demonstrated significant therapeutic efficacy, highlighting its broad clinical potential for the treatment of choroidoretinopathy.

The clinical utility of doxorubicin (DOX) is significantly hampered by its non-selective cytotoxicity and the absence of desirable carriers. While human serum albumin (HSA) represents an excellent candidate for drug delivery, its application is often limited by a weak binding affinity for many therapeutic agents. Herein, a modular strategy was employed to construct HSA-based DOX prodrug nanoparticles (DOX-C14 &HSA NPs) to overcome these deficiencies. To improve tumor selectivity and the HSA-binding affinity of DOX, a pH-sensitive prodrug (DOX-C14) was first synthesized by conjugating DOX to myristic acid (C14) through a hydrazone linkage. Subsequently, through a simple sonication method and by regulating the optimal mass ratio of DOX-C14 to HSA at 1:1.5, we successfully produced DOX-C14 &HSA NPs that exhibited high stability, high encapsulation efficiency and significant drug loading. DOX-C14 &HSA NPs significantly improved the circulation time of DOX and efficiently released free DOX inside tumor cells, causing DNA damage and thus killing tumor cells. Consequently, this work not only overcomes the limitations of DOX but also introduces a new strategy applicable to other drugs for creating HSA-based nano-drugs, thereby broadening the potential of HSA in cancer therapy.

Artemisinin derivatives show antitumor potential via their peroxide bridge, but dihydroartemisinin (DHA) suffers from poor solubility and limited targeting. In this study, inspired by artesunate (ART), we synthesized two derivatives, DHA-CC and DHA-SS, and prepared their PEGylated nanoassemblies (pNAs) using DSPE-PEG2K to enhance their in vivo stability and prolong circulation. Between the two derivatives, DHA-SS pNAs, with their unique disulfide bond structure, demonstrated superior stability, circulation time, and tumor accumulation. Importantly, DHA-SS pNAs exhibited specific responsive drug release under the reductive tumor microenvironment (TME), thereby achieving a favorable balance between systemic stability and efficient activation at the tumor site. In vitro and in vivo evaluations demonstrated that DHA-SS pNAs have higher reactive oxygen species (ROS) generation, greater cytotoxicity, and enhanced antitumor effects without evident systemic toxicity. Overall, these findings demonstrate that this rational structural modification offers a promising strategy for advancing artemisinin-based antitumor therapies toward clinical translation.

Prodrug nanoassemblies (NPs) have attracted much attention in improving the selectivity of chemotherapy drugs, while most of them suffer from poor targeting efficiency. Biotin, a well-known tumor-targeting ligand, can greatly enhance tumor accumulation. Herein, we construct the biotinylated prodrug (BiotinPTX) by connecting paclitaxel (PTX) to biotin via a disulfide bond, enabling the prodrug to self-assemble into nanoparticles (Biotin-PTX NPs). However, the pure NPs are observed to be rapidly cleared without polyethylene glycol (PEG) modifying, while excessive PEG can compromise their targeting efficiency, suggesting that it is crucial to optimize the amount of PEG. On this basis, the effect of distearoyl phosphatidylethanolamine-polyethylene glycol20 0 0 (DSPE-PEG2k ) ratios (0 %, 5 %, 10 %, 20 %, 40 % and 60 %, WPEG /Wprodrug + PEG ) on their performance have been investigated. The results provide evidence that BiotinPTX NPs containing 20 % DSPE-PEG2k (20 % NPs) can significantly improve colloidal stability and tumortargeting efficiency. Moreover, 20 % NPs exhibits good antitumor efficacy and safety compared with Taxol, Abraxane and Prodrug Sol. This work highlights the key role of moderate PEGylation in regulating the therapeutic performance of targeting NPs, offering a new way of thinking for tumor-targeting treatment. (c) 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

The self-assembly prodrugs can be classified into hydrophobic and amphiphilic prodrugs. While hydrophobic prodrugs can form nanoassemblies through strong hydrophobic interactions, these tend to aggregate due to the high surface free energy. Amphiphilic prodrugs reduce surface energy but often lack a sufficient hydrophobic driving force for stable self-assembly. To overcome these limitations, we developed a prodrug coassembly strategy using a hydrophobic paclitaxel-palmitic acid (PA) prodrug (PTX-SS-PA) and three amphiphilic paclitaxel-oligoethylene glycol (OEG) prodrugs (PTX-SS-OEG1, PTX-SS-OEG4, and PTX-SS-OEG8). The results showed that coassembled nanoassemblies exhibit higher stability than self-assembled nanoassemblies. Furthermore, this study indicated that the cellular uptake efficiency, redox-sensitive activation efficiency, and cytotoxicity of coassembled nanoassemblies were affected by the OEG chain length. Notably, the OEG1@PA NPs exhibited the best tumor selectivity and redox-sensitive activation efficiency, resulting in potent antitumor activity and favorable safety. These findings present promising strategies for the development of advanced prodrug nanoassemblies.

Nanodrug delivery systems show great potential in cancer therapy. However, conventional spherical nanoparticles are rapidly recognized and cleared by the mononuclear phagocyte system (MPS). This results in shortened circulation and inadequate tumor accumulation, which ultimately compromises the therapeutic efficacy. Previous studies have suggested that anisotropic morphologies, such as rod-like or worm-like nanostructures, can prolong blood circulation and promote tumor tissue-specific distribution. Nevertheless, controlling the morphology of nanoparticles without altering their chemical composition remains a significant challenge. In this study, we report a novel strategy for physical morphology regulation using prodrug nanoassemblies as a model. Specifically, this process refers to a noncovalent, energy-driven structural reorganization that proceeds without chemical bond cleavage or formation. An ultrasound-assisted one-step nanoprecipitation method is employed to controllably transform thioether-linked SN38 prodrugs (SN38-S-OA) from spherical nanoassemblies into highly uniform nanorods (NRs) with aspect ratios (AR) of 5 or 8. In contrast, the disulfide linkage provides more structural defects, which hinders similar structural reorganizations. Biological evaluations demonstrated that SN38-S-OA NRs AR5 achieved reduced macrophage uptake, prolonged blood circulation, enhanced tumor accumulation, and superior antitumor efficacy compared with those of SN38-S-OA NPs and SN38-SS-OA NPs. Additionally, an optimal aspect ratio is identified, as overly elongated SN38-S-OA NRs AR8 exhibited reduced tumor cell uptake due to increased steric hindrance. This study establishes purely physical morphology regulation as an independent design principle that prolongs circulation, enhances tumor targeting, and improves the therapeutic efficacy in nanomedicine.

Invasive pulmonary fungal diseases (IPFD) represent a growing global health crisis, with escalating incidence and mortality rates, posing a particularly life-threatening risk to immunocompromised populations. The complexity of diagnosis, limited therapeutic options, and the growing challenge of antifungal resistance have significantly constrained the clinical efficacy, leading to poor patient outcomes. Recently, the integration of revolutionary drug delivery platforms with classical antifungal agents, such as optimized nebulized amphotericin B, voriconazole-loaded liposomes and inhalable amphotericin B microspheres, has demonstrated significant clinical potential, particularly in pulmonary applications, by markedly enhancing biodistribution at the infection site while substantially minimizing systemic adverse effects. This comprehensive review synthesized recent advances in IPFD research, encompassing epidemiological characteristics, molecular pathogenesis, clinical manifestations, cutting-edge diagnostic technologies (including advanced imaging, fungal-specific biomarkers and molecular techniques like polymerase chain reaction (PCR) and next-generation sequencing) as well as formulation-based therapeutics that optimize pulmonary targeting to improve efficacy and reduce systemic toxicity. This review aimed to provide insights for the future development of precision-targeted delivery mechanisms and next-generation antifungal agents.

Carbon monoxide (CO)-involving gas therapy, with advantages of high transmembrane diffusivity, multiple pharmacodynamic functions, and non-resistance, holds tremendous potential in cancer therapeutics. However, the main challenges of medicinal CO come from poor tumor targeting and high toxicity. The development of stimuli-responsive CO-releasing molecules (CORMs) enables controlled CO release and reduced gas poisoning. Particularly, advancements in stimulus-ignited nanogenerators built on CORMs create new avenues for precision targeting of malignant tumors and gas-sensitized synergistic therapy. This review initially elucidates the association between CO and tumor progression, and discusses the significance of designing stimulus-ignited CO nanogenerators from the perspective of the dilemma and opportunity of CO treatment. Then, the applications and rationale of CO nanogenerators in spatiotemporally targeted cancer therapy are outlined from different stimulation modalities, highlighting the recent advancements and their primary synergistic effects with other cancer therapeutic paradigms. Finally, the challenges and possibilities of the emerging CO nanogenerators for cancer gas therapy are discussed. This review elucidates the design strategy of stimulus-responsive CO nanogenerators and their synergistic mechanism in precision tumor therapy, which lays down a theoretical framework for the paradigm shift of CO from lethal toxin to therapeutic agent.

The advent of the most representative commercially available formulations of paclitaxel, Taxol and Abraxane, resolved the intravenous challenge of paclitaxel by increasing the water solubility. How-ever, the severe excipient-related toxicity and poor stability of Taxol, along with the low drug loading (10%), complex preparation processes, and poor tumor selectivity of Abraxane, present significant clini-cal dilemma. To overcome the challenges, 16-methylheptadecanoic acid (16-MH), with excellent biocom-patibility was selected as the assembly module. The paclitaxel-16-MH prodrug nanoassemblies (PSSMH NPs) were constructed by conjugating 16-MH with redox-sensitive disulfide bonds and paclitaxel through an ethylene glycol, PSSMH NPs featured the advantages of easy preparation, high drug loading (> 50%) and superior stability (stable storage for 60 days at 25 degrees C). Notably, the area under the concentration-time curve (AUCo34) of PSSMH NPs was 14.95-fold compared with Taxol, indicating a significant improve-ment in the in vivo fate of paclitaxel. Moreover, the existence of redox-sensitive disulfide bonds endowed PSSMH NPs with increased tumor selectivity, resulting in exceptional tolerance and antitumor efficacy. Overall, the redox-triggered prodrug nano-system with high tumor selectivity and biocompatibility ex-hibits substantial potential for clinical translation. 2026 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Dendritic cell (DC) vaccines have made substantial progress in cancer immunotherapy; however, their efficacy is still limited by the transient in vivo fate of mature DCs and suboptimal lymphatic transport. Here, we report a metabolically glycoengineered, nanovesicle-based and personalized nanovaccine (GSNVs) that displays upregulated C-C chemokine receptor 7 (CCR7) and major histocompatibility (MHC)-I complexes to promote lymph node homing and effectively presents tumor antigens to CD8+ T cells, ultimately triggering a strong antigen-specific antitumor immune response. GSNVs were generated from ManNAc-engineered bone marrow-derived DCs (BMDCs) pulsed with highly immunogenic exosomes derived from senescent tumor cells. Metabolic glycoengineering endows BMDCs with enhanced antigen cross-presentation, elevated CCR7 expression, and negligible PD-L1 levels, thereby promoting robust and persistent CD8+ T cell responses. Notably, GSNVs treatment elicits robust antitumor immunity, rescues T cell exhaustion, and markedly inhibits tumor growth of B16-OVA-bearing mice. Collectively, these results reveal that our metabolically glycoengineered GSNVs could be an effective strategy to overcome the inherent limitation of DC vaccines in inducing adaptive antitumor immunity for its potential application in personalized cancer immunotherapy.

Despite demonstrating significant anti-tumor potential as an artemisinin derivative, artesunate faces delivery efficiency challenges due to low water solubility and insufficient targeting specificity. To improve the delivery efficiency, we engineered three artesunate (ART) derivatives, AC15 -L (linear), AC15 -B (branched), and AC15 -C (cyclic) with distinct aliphatic chain architectures. Unexpectedly, we observed that AC15 -C exhibited superior cytotoxicity against 4T1 breast cancer cells, and had the highest binding affinity for Lon protease 1 (LONP1) (-72.6 kcal/mol). Subsequently, disulfide bond-containing lipid-PEG (DSPESS-PEG2K ) modified chain architecture-engineered ART derivatives nanoassemblies (NAs) were developed to mitigate solubility-related limitations while enhancing targeting precision. Molecular docking and experimental validation demonstrated that ART derivatives inhibited LONP1 through hydrophobic interactions while preserved Fe2 + -mediated Fenton-like reaction activity. In vitro and in vivo evaluations demonstrated that AC15 -C NAs outperformed free ART and other NAs, suppressing 4T1 tumor growth via dual action: LONP1-directed mitochondrial proteostasis collapse and reactive oxygen species (ROS) amplification through Fe2 + -ART interactions. This study elucidated a novel anti-tumor mechanism of ART through the rational design of derivatives with spatially configured aliphatic chains, and developed reductionresponsive NAs to provide an advanced delivery strategy. (c) 2025 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Cancer immunotherapy has revolutionized oncologic treatment, yet its efficacy remains constrained by tumor immune evasion and the immunosuppressive tumor microenvironment. Addressing these multifaceted barriers calls for strategies that can both eliminate cancer cells and simultaneously amplify antitumor immunity. Pyroptosis, a lytic and highly immunogenic form of programmed cell death mediated by gasdermin proteins, has recently emerged as a compelling approach to reprogram the tumor immune landscape. By releasing abundant damage-associated molecular patterns and pro-inflammatory cytokines, pyroptosis not only destroys tumor cells but also promotes antigen presentation and robust local-to-systemic immune responses. With the rapid advancement of nanotechnology, pyroptosis-engineered nanomedicine has gained increasing interest for synergizing cell killing and immune activation to enhance cancer immunotherapy. This review summarizes recent progress in the molecular mechanisms of pyroptosis and highlights emerging nanomedicine strategies designed to precisely induce pyroptosis within tumors. The discussion further extends to design principles, activation modalities, and therapeutic outcomes in preclinical models. Finally, current challenges and future directions toward clinical translation are outlined. Collectively, this review integrates pyroptosis biology with nanoengineering concepts to inspire next-generation immunotherapeutic interventions against cancer.

Diabetic wounds are notoriously refractory to healing due to a self-perpetuating pathological microenvironment, perpetuated by a synergistic interplay of oxidative stress, chronic inflammation, infection, and metabolic dysregulation. Conventional therapeutic strategies often fail to dynamically respond to these challenges or achieve synergistic, multi-targeted interventions. Recently, nanoenzyme-engineered hydrogels have emerged as a promising platform for reprogramming the diabetic wound microenvironment by combining the catalytic activity of nanoenzymes with the dynamic responsiveness of hydrogels. This review comprehensively summarizes recent advancements in nanoenzyme-engineered hydrogels for diabetic wound healing. We begin by delving into the core pathological mechanisms that sustain the hostile microenvironment of diabetic wounds. Subsequently, we catalog the development of rationally designed synergistic nanoenzyme-engineered hydrogels, highlighting precision engineering strategies that tailor catalytic functionalities to specific clinical demands. Furthermore, we elucidate the fundamental mechanisms and multifaceted interactions through which these catalytic systems drive microenvironmental reprogramming. Ultimately, this review aims to establish a solid theoretical framework and offer valuable technical insights to guide the development of next-generation nanoenzyme-engineered hydrogels for effective diabetic wound repair.