Albumin-based therapeutics are widely used in cancer treatment for their biocompatibility and hydrophobic drug-loading capacity, but their efficacy is often limited by poor target specificity and weak binding affinity. Inspired by the multivalent and cooperative binding of immunoglobulin M (IgM), we developed a biomimetic tandem Y-shaped Sgc8 aptamer-albumin delivery system (TYS-HSA). By grafting two hydrophilic aptamers onto each hydrophobic C18 side chain of poly(maleic anhydride-alt-1-octadecene) (C18PMH), we constructed well-defined multivalent aptamer units that self-assembled with human serum albumin (HSA) into an IgM-like ligand corona. Quantitative analysis revealed a high ligand valency of approximately 240 aptamers per TYS-HSA nanoparticle, which, combined with its tandem Y-shaped topology, enables cooperative multivalent recognition. This design achieved high-affinity, stable target recognition while maintaining strong loading capacity for hydrophobic drugs such as paclitaxel. Compared with lower-valency conjugates (MS-HSA, approximately 95 aptamers per nanoparticle), TYS-HSA showed enhanced target binding, prolonged cellular retention, and potent antitumor efficacy after a single intravesical administration in an orthotopic bladder cancer model. With broad drug compatibility and excellent physiological stability, this platform offers a promising and generalizable strategy for the targeted design of albumin-based nanomedicines.

mRNA vaccines hold remarkable promise for cancer immunotherapy, yet current nanoparticle systems face challenges in efficacy, dendritic cell (DC) targeting, and safety. Herein, we report a nanoplatform, Manganese‐Coordinated Polyvalent Aptameric System (COMPASS), enabling targeted co‐delivery of mRNA and Mn 2 + to lymph node dendritic cells (DC) to boost potent antitumor immunity. The COMPASS employed rolling circle amplification to generate single‐stranded DNA scaffolds with multivalent DC‐targeting aptamers and polyT domains, enabling stable mRNA hybridization via A‐T pairing. Various metal ions were screened, and Mn 2 + was found to enhance mRNA endosomal escape and activate the STING pathway in DCs, promoting their maturation and antigen presentation. Controlled nanoparticle size (∼200 nm) and aptamer‐mediated DC targeting markedly enhanced lymphatic accumulation. In vivo evaluations revealed that COMPASS achieved potent prophylactic and therapeutic antitumor efficacy comparable to commercial LNPs (e.g., SM‐102), while exhibiting significantly enhanced safety profiles. Importantly, lyophilized COMPASS formulations retained their structural integrity and bioactivity for at least three months at room temperature. Overall, COMPASS represents a promising next‐generation nanoplatform with significant translational potential for safe and effective cancer immunotherapy.

Bacterial infection, insufficient angiogenesis, and oxidative damage are generally regarded as key issues that impede wound healing, making it necessary to prepare new biomaterials to simultaneously address these problems. In this work, monodispersed CeO2@CuS nanocomposites (NCs) were successfully prepared with tannin (TA) as the reductant and linker. Due to abundant oxygen vacancies in CeO2 and the polyphenolic structure of TA, the TA-CeO2@CuS NCs exhibited a remarkable antioxidant ability to scavenge excessive reactive oxygen species (ROS), which would likely induce serious inflammation. In addition, the TA-CeO2@CuS NCs demonstrated excellent antibacterial capability with near-infrared ray (NIR) irradiation, and the released copper ions could promote the regeneration of blood vessels. These synergistic effects indicated that the synthesized TA-CeO2@CuS NCs could serve as a promising biomaterial for multimodal wound therapy.

The progression of atherosclerosis (AS) is marked by escalating chronic inflammation and oxidative stress within the arterial wall, which heightens the risk of plaque rupture and subsequent acute ischemic cardiovascular and cerebrovascular events. Conventional anti-inflammatory and antioxidant therapies, however, are often limited by modest efficacy and potential side effects. Here, we synthesized iron-curcumin coordination polymers (Fe-Cur CPs) coordinated by trivalent iron ions and the natural product curcumin (Cur). These Fe-Cur CPs effectively scavenged excessive reactive oxygen species (ROS) in endothelial cells and macrophages, significantly reduced monocyte adhesion to activated endothelial cells, and attenuated the production of inflammatory factors by macrophages, thereby demonstrating potent antioxidant and anti-inflammatory properties. Additionally, they inhibited foam cell formation. In atherosclerotic ApoE -/- mice, intravenous administration of Fe-Cur CPs significantly reduced plaque burden. Furthermore, these nanoparticles mitigated macrophage aggregation within plaques, effectively inhibited ROS levels and inflammatory cytokine production, enhanced collagen deposition and α-smooth muscle actin (α-SMA) levels, and downregulated matrix metalloproteinase 9 (MMP9) levels, thereby collectively contributing to plaque stabilization. This study proposed a safe and efficient self-assembly strategy for constructing multifunctional coordination polymers that possessed drug-delivery capabilities. These nanoparticles can synergistically modulate multiple risk factors in the atherosclerotic plaque microenvironment, thereby offering a promising therapeutic approach for the treatment of AS.

Single-atom enzymes (SAEs), integrating the catalytic efficiency of single-atom catalysts with enzymatic functions, represent a paradigm shift in biomedicine. Comprising natural enzymes, mimic enzymes, and single-atom nanozymes, SAEs leverage isolated metal atoms as catalytic centers. Natural enzymes, evolved over billions of years, feature monoatomic active sites for precise biocatalysis under physiological conditions. Mimic enzymes (e.g., DNAzymes) represent a biomimetic adaptation, replicating natural active sites via programmable molecular scaffolds to enhance stability while inheriting an evolutionary bias that prioritizes structural robustness over catalytic diversity, limiting multifunctionality. In contrast, nanozymes embody an evolutionary leap: they sacrifice partial biocompatibility to achieve multienzyme-mimicking capabilities and scalable production through inorganic nanomaterial engineering, thereby expanding the catalytic landscape beyond biological boundaries, though this advancement introduces concomitant immunogenicity challenges. This review systematically examines cutting-edge advances in SAE applications across biomedical domains including biosensing, oncotherapy, antimicrobial strategies, and oxidative stress management. This review particularly presents a critical analysis of current challenges and emerging opportunities, proposing rational design principles for next-generation SAEs with enhanced multifunctionality. By elucidating fundamental design strategies and translational potential, this work aims to accelerate the development of precision catalytic platforms for modern biomedicine.

Enzymes with ingenious structures and diverse functions are crucial for biomedical applications but face challenges like instability, limited targetability, and delivery complexity. We developed core-shell DNA-enzyme conjugates using rolling circle amplification (RCA), creating RCA-based DNA-enzyme nanostructure (RCA-DEN) for efficient enzyme immobilization and functionalization. RCA-DEN, characterized by densely packed nucleic acids and negligible disruption of enzyme activity, increases the stability of enzymes and nucleic acids while reducing technical difficulties, making it a versatile platform for diverse biomedical applications. This approach facilitates the modular customization of enzymes and the incorporation of functionalities such as aptamers and DNAzymes. The efficacy of RCA-DEN has been demonstrated in several areas, including selective catalysis, cascade catalysis, dynamic monitoring of intracellular chemical processes, and synergistic therapeutic interventions against tumors. Overall, this work provides a new perspective on enzyme immobilization and functionalization, paving the way for broader biomedical applications of enzymes.

Diabetic wounds are refractory and recurrent chronic conditions, characterized by insufficient tissue nutrition, persistent infection, and immune dysregulation. These challenges underscore the need for innovative, multifunctional wound dressings. In this study, we synthesized cobalt-doped FeS₂ (Co-FeS₂) nanozymes that exhibit superior peroxidase (POD)-like and superoxide dismutase (SOD)-like activities, enhanced photothermal performance, and greater antioxidant capacity compared to Fe₃O₄ and FeS₂. The Co-FeS₂ nanozyme was encapsulated together with H₂O₂ in a hydrogel matrix composed of polyvinyl alcohol (PVA)-borax modified with sodium alginate (SA) and tannic acid (TA), resulting in a material with strong skin adhesion, self-healing property, and excellent biodegradability. The incorporated H₂O₂ serves a dual purpose: it regulates the hydrogel's degradation kinetics and provides early-stage antibacterial activity through reactive oxygen species (ROS) generation, while subsequently being catalyzed by Co-FeS₂ to produce oxygen. This oxygen supply, along with ROS scavenging, promotes the polarization of pro-inflammatory M1 macrophages to anti-inflammatory M2 macrophages, thereby resolving chronic inflammation. Both in vitro and in vivo evaluations demonstrated that the composite hydrogel possesses excellent biocompatibility, sustained antibacterial efficacy, antioxidant activity, anti-inflammatory regulation, and pro-angiogenic effects. These findings highlight its potential as a promising wound dressing for diabetic and other chronic wounds, effectively addressing multiple pathological challenges in the healing process.

Preparation for the potential emergence of future human coronaviruses (HCoVs) calls for the development of versatile and effective treatment strategies. The signs and symptoms of HCoVs include an immune inflammatory response. Therefore, our study focuses on the simultaneous inhibition of HCoV infection and the alleviation of lung inflammation. Inspired by conformational epitope matching, we engineered a de novo antigen spatial-matching polyaptamer (ASM-pApt) nanostructure designed to align perfectly with multiple spike (S) proteins on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus (PsV). Compared with monovalent aptamer, the dissociation constant (K-D) of the ASM-pApt nanostructure decreased by over 1,000-fold, and its viral semi-inhibitory concentration (IC50) improved by over 100,000fold to 89.7 fM (fmol/L), indicating the effectiveness of antigen spatial matching. By loading polyphenol as anti-inflammatory drug and chitosan (CS) as an excipient, the ASM- pApt nanostructure showed anti-inflammatory and long drug retention properties. Our design shows the promise of polyaptamer as an antiviral/antiinflammatory candidate against emerging HCoVs in the future.

The fast multipole method (FMM) based on the plane wave expansion is known to suffer from numerical instability in the low-frequency regime. This paper presents a low-frequency fast multipole boundary element method (LF-FMBEM) for acoustic problems in a subsonic uniform flow. First, a hybrid convected boundary integral formula based on the Burton-Miller method is derived to overcome the non-uniqueness difficulty at fictitious eigenfrequencies. The explicit evaluation of hypersingular integrals in the convected boundary integral formulae is also introduced. Then, the formulae of FMM based on the series expansion for convected BEM are derived to improve the calculation efficiency. The recursive calculation method is derived in the expansion of the derivative of the integrands. Besides, the rotation-coaxial translation-rotation back (RCR) technique is employed to accelerate the multipole translation. The numerical implementation process of the developed algorithm is presented in detail. Several numerical experiments are performed to validate the computational efficiency and accuracy of the developed LF-FMBEM. Results show that the proposed algorithm can achieve large-scale computation of one million degrees of freedom (DOF) on a personal computer, and the computational accuracy is still high when the Mach number reaches 0.95. The non-uniqueness problem for convected acoustics problems is also effectively overcome.

Patients with methicillin-resistant Staphylococcus aureus (MRSA) infections may have higher death rates than those with non-drug-resistant infections. Nanozymes offer a promising approach to eliminating bacteria by producing reactive oxygen species. However, most of the conventional nanozyme technologies encounter significant challenges with respect to size, composition, and a naturally low number of active sites. The present study synthesizes a iron-single-atom structure (Fe-SAC) via nitrogen doped-carbon, a Fe-N5 catalyst (Fe-SAC) with a high metal loading (4.3 wt.%). This catalyst permits the development of nanozymes consisting of single-atom structures with active sites resembling enzymes, embedded within nanomaterials. Fe-SAC displays peroxidase-like activities upon exposure to H2O2. This structure facilitates the production of hydroxyl radicals, well-known for their strong bactericidal effects. Furthermore, the photothermal properties augment the bactericidal efficacy of Fe-SAC. The findings reveal that Fe-SAC disrupts the bacterial cell membranes and the biofilms, contributing to their antibacterial effects. The bactericidal properties of Fe-SAC are harnessed, which eradicates the MRSA infections in wounds and improves wound healing. Taken together, these findings suggest that single Fe atom nanozymes offer a novel perspective on the catalytic mechanism and design, holding immense potential as next-generation nanozymes.

Cuproptosis, a copper-dependent cell death process, has been confirmed to further activate the immune response and mediate the immune resistance. However, hypoxic tumor microenvironment hampers cuproptosis sensitivity and suppresses the body's antitumor immune response. Herein, we have successfully immobilized and functionalized catalase (CAT) with long single-stranded DNA containing polyvalent CpG sequences through rolling circle amplification (RCA) techniques, obtaining an enzyme-cored spherical nucleic acid nanoplatform (CAT-ecSNA-Cu) to deliver copper ions for cuproptosis. The presence of long-stranded DNA-protected CAT enhances mitochondrial respiration by catalyzing the conversion of H2O2 to O2, thereby sensitizing cuproptosis. Meanwhile, increased tumor oxygenation suppresses the expression of the hypoxia-inducible factor-1 (HIF-1) protein, resulting in the alleviation of the immunosuppressive tumor microenvironment. Of note, cuproptosis induces immunogenic cell death (ICD), which facilitates dendritic cell (DC) maturation and enhances antigen presentation through polyCpG-supported Toll-like receptor 9 (TLR9) activation. Furthermore, cuproptosis-induced PD-L1 upregulation in tumor cells complements checkpoint blockers (αPD-L1), enhancing antitumor immunity. The strategy of enhancing cuproptosis-mediated antitumor immune responses by alleviating hypoxia effectively promotes the activation and proliferation of effector T cells, ultimately leading to long-term immunity against cancer.

Nanomaterial-based in vivo tumor imaging and therapy have attracted extensive attention; however, they suffer from the unintelligent "always ON" or single-parameter responsive signal output, substantial off-target effects, and high cost. Therefore, achieving in vivo easy-to-read tumor imaging and precise therapy in a multi-parameter responsive and intelligent manner remains challenging. Herein, an intelligent DNA nanoreactor (iDNR) was constructed following the "AND" Boolean logic algorithm to address these issues. iDNR-mediated in situ deposition of photothermal substance polydopamine (PDA) can only be satisfied in tumor tissues with abundant membrane protein biomarkers "AND" hydrogen peroxide (H2 O2 ). Therefore, intelligent temperature-based in vivo easy-to-read tumor imaging is realized without expensive instrumentation, and its diagnostic performance matches with that of flow cytometry, and photoacoustic imaging. Moreover, precise photothermal therapy (PTT) of tumors could be achieved via intelligent heating of tumor tissues. The precise PTT of primary tumors in combination with immune checkpoint blockade (ICB) therapy suppresses the growth of distant tumors and inhibits tumor recurrence. Therefore, highly programmable iDNR is a powerful tool for intelligent biomedical applications.

Piezocatalytic therapy (PCT) based on 2D layered materials has emerged as a promising non-invasive tumor treatment modality, offering superior advantages. However, a systematic investigation of PCT, particularly the mechanisms underlying the reactive oxygen species (ROS) generation by 2D nanomaterials, is still in its infancy. Here, for the first time, biodegradable piezoelectric 2D bilayer nickel-iron layered double hydroxide (NiFe-LDH) nanosheets (thickness of ≈1.86 nm) are reported for enhanced PCT and ferroptosis. Under ultrasound irradiation, the piezoelectric semiconducting NiFe-LDH exhibits a remarkable ability to generate superoxide anion radicals, due to the formation of a built-in electric field that facilitates the separation of electrons and holes. Notably, the significant excitonic effect in the ultrathin NiFe-LDH system enables long-lived excited triplet excitons (lifetime of ≈5.04 µs) to effectively convert triplet O2 molecules into singlet oxygen. Moreover, NiFe-LDH exhibited tumor microenvironment (TME)-responsive peroxidase (POD)-like and glutathione (GSH)-depleting capabilities, further enhancing oxidative stress in tumor cells and inducing ferroptosis. To the best of knowledge, this is the first report on piezoelectric semiconducting sonosensitizers based on LDHs for PCT and ferroptosis, providing a comprehensive understanding of the piezocatalysis mechanism and valuable references for the application of LDHs and other 2D materials in cancer therapy.

The excessive release of reactive oxygen species (ROS) after myocardial infarction (MI) disrupts the natural healing process, leading to cardiac fibrosis and compromising patient prognosis. However, the clinical application of many antioxidant drugs for MI treatment is hindered by their poor antioxidant efficacy and inability to specifically target the heart. Here we developed a tannic acid-modified MnO2 nanozyme (named MnO2@TA), which can achieve cardiac targeting to inhibit post-MI fibrosis and enhance cardiac function. Specifically, the MnO2@TA nanozyme, endowed with superoxide dismutase (SOD) and catalase (CAT) activities, effectively scavenges ROS, suppressing fibroblast activation and mitigating cardiac fibrosis without affecting cardiac repair. Notably, the incorporation of TA improves the nanozyme’s affinity for the elastin and collagen-rich extracellular matrix in cardiac tissues, significantly increasing its retention and uptake within the heart and thereby enhancing its anti-fibrotic efficacy. In a murine myocardial infarction model, MnO2@TA demonstrates remarkable cardiac protection and safety, significantly improving cardiac function while attenuating cardiac fibrosis. This study presents a valuable reference for clinical research aimed at inhibiting cardiac fibrosis and advancing myocardial infarction treatments.

Cuproptosis, a recently identified form of copper-dependent cell death, shows promising tumor suppressive effects with minimal drug resistance. However, its therapeutic efficacy is hampered by its dependence on copper ions and the glutathione (GSH)-rich microenvironment in tumors. Here, we have developed polyvalent aptamer nanodrug conjugates (termed CuPEs@PApt) with a nucleosome-like structure to improve tumor cuproptosis therapy by exploiting mitochondrial copper overload and GSH depletion. Polyvalent aptamer (PApt), comprising polyvalent epithelial cell adhesion molecule aptamers for tumor targeting and repetitive PolyT sequences for copper chelation, facilitates efficient loading and targeted delivery of copper peroxide-Elesclomol nanodots (CuPEs). Upon internalization by tumor cells, Elesclomol released from CuPEs@PApt accumulates copper ions in mitochondria to initiate cuproptosis, while lysosomal degradation of CuP nanodots generates exogenous Cu2+ and H2O2, triggering a Fenton-like reaction for GSH depletion to enhance cuproptosis. In vitro and in vivo experiments confirm the efficacy of this strategy in inducing tumor cell cuproptosis and immunogenic cell death, the latter contributing to the activation of the antitumor immune response for synergistic tumor growth inhibition.

Bacterial infections are a growing global public health problem, exacerbated by the widespread and often inappropriate use of antibiotics, leading to the emergence of non-antibiotic pathogens. Herein, we synthesized a chitosan-Prussian blue nanozyme (CS@PB), a non-antibiotic agent, for universal antibacterial and anti-inflammatory treatment of bacterial infections. Confocal microscopy images showed that CS@PB significantly enhanced the physical interaction between chitosan and bacteria, thereby increasing the antibacterial ability. Moreover, these nanozymes exhibited potent antioxidant and anti-inflammatory properties, promoting macrophage polarization toward the M2-like phenotype, reducing oxidative stress, and alleviating inflammation. This dual-action approach effectively accelerates the healing of bacteria-infected inflammatory wounds. The synergistic bactericidal and anti-inflammatory properties of CS@PBs inhibited wound infection and promoted the healing of skin infections in a mouse model. In addition, CS@PB displayed remarkable lung retention and potent bactericidal effects, resulting in significantly improved survival rates in mouse models of acute pulmonary bacterial infections. In conclusion, CS@PBs exhibited exceptional bactericidal capabilities, anti-inflammatory properties, and minimal toxicity, suggesting that they are promising candidates for a new generation of non-antibiotic antimicrobial agents for the treatment of bacterial infections.

Single-atom catalysts (SACs) with atomically dispersedactive sitesand maximum atomic utilization efficiency provide new opportunitiesto develop high-performance nanozymes. However, the preparation ofSACs with a high metal content still faces serious challenges. Herein,we report a pyrolysis method for achieving a Cu single-atom catalyst(Cu-SAC) on nitrogen-doped carbon with a Cu loading of 7.98 wt %.Isolated Cu atoms with Cu-N-3-C coordinationwere confirmed by spherical aberration-corrected transmission electronmicroscopy and X-ray absorption spectroscopy. The synthesized Cu-SACdisplayed outstanding peroxidase-like activity by effectively catalyzingthe reaction between 3,3 ',5,5 '-tetramethylbenzidine(TMB) and H2O2 to show a blue color. Based onthe inhibition effect on the oxidation of TMB by ascorbic acid (AA),a colorimetric assay for AA was established with a limit of detection(LOD) of 0.63 mu M. Furthermore, the total antioxidant capacities(TACs) of practical samples including vitamin C tablets, commercialbeverages, and fresh fruit were successfully detected by the proposedcolorimetric assay. This study provided a facile method for the preparationof high-metal-loading SACs, which exhibited high enzymatic propertieswith promising applications in food and drug safety.

Current clinical approaches to osteoporosis primarily target osteoclast biology, overlooking the synergistic role of bone cells, immune cells, cytokines, and inorganic components in creating an abnormal osteoporotic microenvironment. Here, metal-polyDNA nanoparticles (Ca-polyCpG MDNs) composed of Ca 2+ and ultralong single-stranded CpG sequences were developed to reconstruct the osteoporotic microenvironment and suppress osteoporosis. Ca-polyCpG MDNs can neutralize osteoclast-secreted hydrogen ions, provide calcium repletion, promote remineralization, and repair bone defects. Besides, the immune-adjuvant polyCpG in MDNs could induce the secretion of osteoclastogenesis inhibitor interleukin-12 and reduce the expression of osteoclast function effector protein to inhibit osteoclast differentiation, further reducing osteoclast-mediated bone resorption. PPi 4− generated during the rolling circle amplification reaction acts as bisphosphonate analog and enhances bone targeting of Ca-polyCpG MDNs. In ovariectomized mouse and rabbit models, Ca-polyCpG MDNs prevented bone resorption and promoted bone repair by restoring the osteoporotic microenvironment, providing valuable insights into osteoporosis therapy.

Comprehensive SummaryNucleic acids are the hereditary information storage medium of life. Due to its high programmability and good biocompatibility, the applications of nucleic acids are not limited to their natural function. However, the efficiency of nucleic acids is often hampered by inherent limitations in numerous practical applications, including limited access to complex functional patterns due to only four building blocks, facile degradation by nucleases, rapid renal clearance, poor pharmacokinetic properties, and so on. To end this, the researchers developed unnatural base pairs (UBPs) and numerous artificial analogues of nucleosides and oligonucleotides in recent decades. The developed UBPs and nucleoside base analogues together constitute artificial nucleobase compilation, which promotes the development of biomedical sciences. Here, we describe the development of artificial nucleobase compilation and summarized its applications in precise molecular medicine, including PCR‐based diagnostics, aptamer‐based diagnostics, nucleobase analogue drugs construction, ASO modification, aptamer‐based therapeutics and biomaterials construction. This review provides an overview of current opportunities and challenges of artificial nucleobase‐related precise molecular medicine.