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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.

Understanding how nanoparticles move near liquid-solid interfaces is central to nanoscale transport in catalysis, biology, and soft materials. Here, we uncover the physical mechanisms governing anomalous surface diffusion of PEG-coated gold nanorods (AuNRs) near the silicon nitride (SiNx) membrane in liquid-phase transmission electron microscopy (LPTEM). By systematically tuning the ionic environment (H2O, 5 mM H2SO4, 1.5 mM NaCl, 5 mM PBS), we show how electrostatic screening and ion-specific surface interactions modulate the interaction landscape, altering the strength and abundance of binding sites that govern the confinement and mobility of nanoparticles. Statistical analyses and deep learning classification of particle trajectories reveal a tunable transition between fractional Brownian motion (FBM) in strongly interacting systems (H2O, H2SO4) and annealed transient time motion (ATTM) in screened environments (NaCl, PBS). These results establish electrostatic screening and specific ion effects as external controls that program near-surface transport, shifting the diffusion mechanism from FBM to ATTM and tuning the particle mobility. To further elucidate the interfacial dynamics, we introduce a passive nanorheology framework in LPTEM, modeling the near-surface environment of FBM-classified conditions as an effective viscoelastic medium. Leveraging translational and rotational trajectories as nanoscale rheological probes, we reconstruct frequency-dependent viscoelastic moduli to extract relaxation times and elastic-to-viscous crossover moduli that report on interaction strength at the SiNx interface. Together, these advances provide both control and diagnosis of interfacial mechanical response in LPTEM, positioning it as a quantitative tool for probing nanoscale transport in complex soft-matter and interfacial systems.

Point-of-care diagnostic tools, such as lateral flow assays (LFAs), play a critical role in disease management and outbreak control. LFAs detect the presence of target antigens in disease-relevant biofluids, utilizing nanoparticles (termed detection probes) to produce colorimetric readouts. However, significant intra- and interpatient variation in the biochemical composition of biofluids has downstream consequences for assay performance. Robust LFAs must be able to function alongside such variability to produce reliable and reproducible test outcomes. Beyond this, biofluids (such as serum) contain significant amounts of proteins, which can interact with detection probes used in LFAs to form a protein corona. The consequences of protein corona formation on LFA performance are poorly understood. Using a model antigen-biofluid LFA (human epidermal growth factor receptor 2 (HER2) and human serum), we observed significant discrepancies in LFA performance when using conventional nanoparticle functionalization methods, including the use of generic, nonhuman protein blocking agents. To overcome these performance differences, we developed a methodology for Bionano interface Optimization for LFA Design (termed BOLD). The BOLD workflow employs mass spectrometry-based proteomics to characterize the native protein corona, followed by formation of an engineered corona to produce an optimized bionano interface. We identified a specific protein (kininogen-1, KNG1) that demonstrated negative interference, significantly reducing the observed LFA test line intensity. This experimental finding is complemented by Molecular Dynamics simulations, which probe the binding modes of KNG1 to platinum nanoparticles. Further, through the employment of an apolipoprotein engineered corona (apolipoprotein A1, B, and C3), a robust LFA was developed, increasing test line intensity and significantly reducing intersample variation (with over a 4-fold improvement in the coefficient of variation). Overall, the BOLD workflow presents a method for the rational optimization of detection probes in LFAs through the characterization of the bionano interface to produce robust LFAs.

Polyelectrolyte multilayer (PEM) membranes have shown great promise in a wide range of membrane-based separations. However, a continuous challenge is the permeability-selectivity trade-off. One method of avoiding this trade-off is by reducing the thickness of the selective layer. However, PEM membranes have a limit to this reduction, as they first have to fill the pores of their support membrane before they can form a defect-free selective layer. To overcome this limitation, we propose the use of nanoparticles as sacrificial pore fillers. Therefore, we first coated SiO2 nanoparticles in the initial bilayer of a poly-(diallyldimethylammonium chloride)/poly-(sodium 4-styrenesulfonate) PDADMAC/PSS PEM to fill the pores of the support membrane and prevent subsequent PDADMAC/PSS bilayers from entering. Subsequently, we dissolved them in a NaOH solution. The results show that the optimal membrane, formulated with 12 nm sacrificial nanoparticles, successfully enhanced the permeability up to 2× (achieving 24 L m-2 h-1 bar-1) while maintaining a comparable molecular weight cutoff (MWCO) of 312 Da. Membranes showed a slight change in ion retentions as the negatively charged membranes lost some of their overall charge due to the dissolution of the negatively charged SiO2 nanoparticles. However, Donnan exclusion remained the dominant separation mechanism. These results establish nanoparticles as effective sacrificial pore fillers, enabling PEM membranes to achieve superior performance compared to commercial nanofiltration membranes by reducing their energy requirements in separation processes.

Antimicrobial photothermal therapy requires nanomaterials that combine high plasmonic performance, colloidal stability, and scalable synthesis. In this work, we prepared bimetallic silver nanoplates partially coated with an ultrathin gold layer in a larger-volume batch (160 mL), while preserving stable optical properties and tunable photothermal performance in the biological near-infrared range. The resulting silver-gold nanoplates efficiently convert near-infrared light into heat and exert potent antimicrobial effects against Pseudomonas aeruginosa and Staphylococcus aureus. Systematic evaluation showed that thiol-terminated polyethylene glycol functionalization preserves the optical response of the nanoplates while improving colloidal stability in biologically relevant media. Furthermore, we investigated the trade-off between multifunctionality, stability, and photothermal efficiency observed after silica coating followed by covalent BSA conjugation, which increases surface functionalization versatility but reduces antimicrobial performance under the tested conditions. This work presents an efficient route to synthesize bimetallic Ag-Au nanoplates in large-volume batch for noninvasive antimicrobial photothermal applications and outlines key design principles to guide the development of next-generation multifunctional plasmonic nanoplatforms for antimicrobial therapy.

Nanopore is a single-molecule technology for sensing biomolecules. Biomolecular interactions are essential biological processes that govern biological functions and therapeutic responses. However, high-resolution nanopore sensing of biomolecular interactions, such as protein-ligand interactions, remains challenging. In this study, we demonstrate that a YaxAB nanopore with LiCl-modulated electrostatic potential enables detection of molecular interactions of the BRD4 protein with histone peptides, as well as diverse small-molecule drugs, at the single-molecule level. Our electrical recordings and molecular dynamics simulations confirm that the oscillating dynamics of BRD4 within the funneled YaxAB nanopore generate two-level current transitions between narrow- and wide-pore regions. Using the parameters derived from dual-level dynamics and their signal decomposition, a YaxAB nanopore sensing approach enables the sensitive discrimination of BRD4-small-molecule drug complexes with a subtle mass difference as small as 2.5 Da. This near-atomic, high-resolution sensing capability of YaxAB nanopores may enable applications in single-molecule-based drug discovery, proteomics, and diagnostics.

Nanozymes with multienzyme-like capabilities can function as self-catalytic reactors, exhibiting significant advantages over natural enzymes. However, it is still challenging to develop a general strategy to regulate the multienzyme-like activities of nanozymes and clarify their intricate catalytic mechanisms. Herein, we establish a seed-mediated strategy to modulate the multienzyme-like activities of gold@cerium oxide (Au@CeO2) by altering the morphology of gold seeds. The end-coated nanostructure exhibits superior phosphatase-like (POP-like) activity compared to the core@shell nanostructure. Through structure-activity correlation, we reveal that Lewis acidity (LA) and oxygen-vacancy density serve as key descriptors governing the POP-like activity, synergistically activating the phosphoester substrate and water nucleophile. This work elucidates the mechanisms underlying morphology-dependent catalytic regulation, offering a rational design strategy for developing hydrolase-mimicking nanozymes.

Revealing dynamic local-structure changes of (sub)nanometric metal species under operating conditions is essential. In heterogeneous catalysis, this insight enables the rationalization of operation and optimization of catalyst efficiency and stability. Extended X-ray absorption fine structure (EXAFS) provides element-specific access to metal-metal coordination numbers, interatomic distances, and local disorder, which is pivotal when active motifs lack long-range order. Yet, accurate determination of structural parameters from EXAFS signatures is often complicated by the convolution of static heterogeneity and thermal vibration effects, encoded in the Debye-Waller factor: σ2=σdynamic2(T)+σstatic2. This coupling, especially at elevated temperatures typical of in situ and operando studies, obscures genuine structural changes. Here we present a temperature-resolved EXAFS study geared toward deconvoluting σdynamic2(T) in three supported Ag catalysts spanning different σstatic2 levels and metal aggregation states: Al2O3-supported Ag nanocrystals, few-atom Ag clusters confined to a zeotype host, and single-atom Ag dispersed on WOx/Al2O3. Over 298-723 K, representative of catalyst activation and deployment conditions, we observe a nuclearity-dependent vibrational stiffness: Ag-Ag bonds in nanoparticles show strong thermal disorder, whereas Ag-O bonds in single-atoms and confined clusters remain comparatively rigid, limiting dynamic fluxionality. While a classical formalism, such as the correlated Einstein model, adequately captures nanocrystal dynamics, it fails for few- and single-atom motifs. Therefore, a direct parametrization of σ2(T) is proposed, better capturing vibrational disorder in low-nuclearity metal catalysts. The results provide guidance for decoupling thermal and static contributions in temperature-resolved EXAFS studies, enabling a more reliable structural analysis of (sub)nanometric metal species under operando conditions.

The development of lightweight, flame-retardant thermal insulation materials capable of withstanding both extreme cold and potential fire hazards continues to be a significant challenge in the field of personal protective equipment. This study presents a facile method based on humidity-induced electrospinning to fabricate polyimide/silica (PI/SiO2) nanofibrous sponges (NFS) for high-performance thermal insulation. Regulating the rapid phase inversion within the whipping jet leads to the formation of a fluffy assembly of curly, porous nanofibers, and the PI nanofibrous sponge is further obtained following the imidization process. Furthermore, the introduction of nano-SiO2 particles creates a synergistic effect with the PI matrix at high temperature, promoting a dense, stable composite carbon layer that significantly improves flame retardancy. The final PI/SiO2-NFS exhibits ultralight property (2.77 mg cm-3), robust mechanical properties (withstand loads 10,000 times its own weight and remarkable elasticity and fatigue resistance), a low thermal conductivity (25.1 mW m-1 K-1), as well as outstanding flame retardancy. This work presents a novel pathway for developing next-generation high-performance thermal protection materials for personal safety in harsh environments.

Understanding degradation mechanisms in halide perovskites under operation is crucial to improving device stability, yet direct nanoscale observation during electrical biasing remains challenging. Here, we report the fabrication of planar nano-perovskite LEDs integrated into an electron-transparent circuit, enabling simultaneous electrical, structural, and optical characterization of perovskite devices directly inside electron microscopes. In situ biasing shows that volatilization of Br2 accompanied by the formation of Pb0, PbBr2, and CsBr phases is significantly more pronounced at the cathodic region, indicating a pathway closely linked to cathodic reduction rather than anodic oxidation. The nano-LEDs also exhibit electroluminescence (EL) within the microscope, enabling temperature estimation via EL tracking, which is valuable for nanoscale devices in operando TEM, where thermal probing is difficult. Cathodoluminescence (CL) mapping further identifies regions susceptible to material loss prior to biasing through a characteristic red shift in the CL spectrum, highlighting the link between local defect density and electrical instability. Remarkably, applying a moderate reverse bias (≤7 V) induced reversibility of the degraded structure, while higher reverse biases promoted defect formation. These results establish a comprehensive in situ platform for probing degradation, recovery, and biasing strategies in perovskite optoelectronic devices.

Diabetes mellitus leads to systemic immunosuppression, increasing susceptibility to persistent infections and elevating the risk of severe complications. Concurrently, multidrug-resistant (MDR) pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) further exacerbate therapeutic difficulties. To address this challenge, we engineered peroxidase (POD)-like nanoassemblies (DC/Cu) through the copper-coordinated self-assembly of ε-poly(L-lysine)-derived carbon dots (CDs) and anti-inflammatory agent diclofenac sodium (DS). These nanoassemblies integrate antibacterial, anti-inflammatory, and tissue-reparative functionalities for the treatment of MDR bacteria-induced diabetic infections. Cationic DC/Cu can selectively adhere to bacterial membranes, enabling microenvironment-responsive spatiotemporal drug release. The POD-like activity of CDs catalyzes the endogenous H2O2, inducing membrane lipid peroxidation and enhancing cell membrane permeability, which facilitates copper influx. This self-cascade induces lethal intracellular copper overload in MRSA, with transcriptomic profiling confirming Cu2+-mediated inhibition of Fe-S cluster proteins and disruption of the tricarboxylic acid cycle, leading to subsequent activation of cuproptosis-like death pathway. Simultaneously, the released DS mitigates the inflammatory response, while Cu2+ facilitates tissue regeneration. MRSA-infected diabetic foot ulcers and diabetic MRSA keratitis models validated DC/Cu's multifunctional efficacy in bacterial eradication, inflammatory mitigation, and tissue regeneration. Collectively, these multifunctional nanoassemblies demonstrate a promising and effective approach for precision therapeutic intervention against MDR pathogen-aggravated diabetic complications.

Cancer therapy is often constrained by targeting single pathogenic mechanisms without addressing the complex tumor microenvironment (TME). Here, we introduce FINAL (Fucoidan-docetaxel Immunomodulatory Nanoparticles as an Antitumoral Lancer), a surface-engineered nanoplatform that simultaneously targets P-selectin-expressing cancer cells and tumor-associated macrophages (TAMs). Beyond targeting specificity, fucoidan surface modification provides intrinsic bioactivities that individually modulate both cell types while coordinately reshaping the TME. FINAL achieves dual-cell orchestration through P-selectin-mediated targeting, activating both receptor-dependent signaling pathways and receptor-independent bioactivities of fucoidan and DTX. P-selectin-mediated targeting enhances cellular uptake and disrupts tumor-TAM adhesion, reducing the level of circulating hybrid cell (CHC) formation. Independent of targeting, fucoidan's bioactivity reduces cellular reactive oxygen species in cancer cells, promotes M1 macrophage polarization, and suppresses VEGF-A-mediated angiogenesis. RNA-seq transcriptomic profiling demonstrated that FINAL drives synergistic immune activation pathways while simultaneously repressing tumor progression signatures, providing mechanistic evidence for concurrent tumor-immune dynamics at the molecular level. In triple-negative breast cancer (TNBC) models, this system-level approach achieved breakthrough therapeutic outcomes, including doubling survival duration, suppressing primary tumor growth, inhibiting lung metastasis, and preserving bone marrow hematopoietic function, demonstrating translational potential compared to conventional docetaxel formulations. Importantly, FINAL maintained therapeutic benefits while reducing systemic toxicity, establishing an optimal balance between antitumor efficacy and safety. The rationally designed fucoidan nanobio interface establishes FINAL as a versatile platform for P-selectin-expressing diseases for next-generation immunochemotherapy agents with broad translational potential across multiple cancer types.

Efficient photodynamic antibacterial activity relies on the close interfacial association between photosensitizers and bacterial surfaces. While cationic functional groups can enhance bacterial binding, they often cause nonspecific membrane disruption and substantial dark toxicity. Here, we demonstrate that engineering a mixed-charge surface on conjugated oligomer nanoparticles enables programmable interfacial interactions and, consequently, controllable antibacterial performance. Charge-complementary conjugated oligomers, OFTF(+) bearing quaternary ammonium groups, and OFTF(-) bearing carboxyl groups, were assembled into photofunctional nanoparticles (OFTFNPs) by controlling their molar ratio. The mixed-charge surface maintained stable bacterial binding while reducing the overly strong electrostatic contact. This shifted the dominant interaction contribution toward hydrophobic association, thereby reducing nonspecific damage. Based on the balanced nano-bio interface, OFTFNPs predominantly generate reactive oxygen species via a Type II mechanism upon light irradiation, achieving the eradication of bacteria with minimal dark toxicity and improved cytocompatibility relative to OFTF(+) alone. These results demonstrate that mixed-charge surface engineering is a practical approach for separating potent photodynamic antibacterial efficacy from cationic dark cytotoxicity in photosensitizer platforms.

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disorder characterized by progressive joint destruction and erosive pathology. Synovitis is considered the hallmark pathological manifestation of RA, often affecting multiple joints throughout the body. Hence, developing strategies for accurate delivery of therapeutics to inflamed joints is crucial to improving drug delivery efficiency. Herein, we rationally constructed a nanosystem that consists of gold nanoparticles serving as both drug carriers and radiosensitizers, fibroblast activation protein inhibitor (FAPI) as a targeting ligand for pathological neovascularization, and β-cyclodextrin (β-CD) as a host matrix for encapsulating BET inhibitor I-BET151. The targeted delivery enabled selective accumulation of I-BET151 at inflamed joints to mitigate immune activation by inhibiting the abnormal proliferation and migration of synovial fibroblasts in collagen-induced arthritis mice. Single-cell profiling dissected this nanosystem effectively suppressing synovial inflammation by eliminating activated B cells and reversing the hypoxia-inducible factor 1-alpha (Hif 1α)-driven profibrotic and migratory program of fibroblast-like synoviocytes. Combined with low-dose radiotherapy, comprehensive transcriptome standardization and cellular remodeling in RA were achieved. Therefore, our strategy holds considerable promise for advancing the management of rheumatoid arthritis and offers a potent therapeutic modality for refractory RA.

Hepatic ischemia-reperfusion injury (IRI), driven primarily by excessive mitochondrial reactive oxygen species (ROS) generation, is a major cause of liver dysfunction, graft failure, and postoperative complications. However, no pharmacological agents have been clinically approved for its prevention or treatment, and there is an urgent need for effective therapeutic strategies. In this study, we established a nanoplatform composed of PEGylated polydopamine nanoparticles modified with the mitochondrial-targeting peptide SS-31 (PPS NPs). SS-31 peptide modification confers PPS NPs with efficient mitochondrial-targeting capability, thereby restoring mitochondrial membrane potential and reducing ROS accumulation in the hypoxia/reoxygenation model. Furthermore, treatment with PPS NPs significantly mitigates liver injury, decreases inflammatory factor levels, and inhibits neutrophil recruitment in mice subjected to IRI. Transcriptome sequencing and metabolomics analyses indicate that PPS NPs can protect the liver from ischemia-reperfusion injury by preserving mitochondrial integrity, reducing ROS generation, and regulating arachidonic acid and glutathione metabolism. By preserving mitochondrial function, maintaining cellular redox homeostasis, and suppressing inflammatory cascades, PPS NPs ultimately inhibit mitochondria-dependent apoptosis and confer protection against liver IRI, providing a practical therapeutic strategy for hepatic IRI clinical management.

Platelet storage remains a critical challenge in transfusion medicine, with current WHO and FDA guidelines limiting storage to just 72 h due to the risk of platelet dysfunction and bacterial contamination. This study examines how platelet adhesion is influenced by the interstructured distance of various microstructured geometries printed by mask-free nanoimprinting fluid force microscopy (FluidFM) technology. Microstructures of multiple geometries (circles, Pacman, lines, grids, and triangles) were printed on glass surfaces using the commercial Loctite AA3491, composed of multiple acrylate monomers, at three different peak-to-peak distances: 10 μm, 5 μm, and 2 μm. Atomic force microscopy (AFM) was employed to characterize the topography and printing precision of these structures. All structures exhibited nanoscale heights and demonstrated high fidelity to the designed patterns. Adhered platelets on the structured surfaces were quantified using confocal laser scanning microscopy. Results demonstrated that platelet attachment is significantly affected by both structural geometry and peak-to-peak distance. Circular and Pacman-like structures consistently showed reduced platelet adhesion, particularly at the largest peak-to-peak distance of 10 μm. Platelet attachment generally increased with decreasing peak-to-peak distance between the microstructures, yet all structured surfaces showed reduced adhesion compared to unstructured glass and nonpatterned Loctite, indicating that microtopographical modifications can effectively inhibit platelet attachment. Our results provide insights into designing antifouling surfaces for medical applications, demonstrating the potential of FluidFM technology in fabricating precision microstructures to mitigate platelet attachment as a mechanistic model to study geometry-dependent platelet-surface interactions.

The preservation of physiological thermal homeostasis serves as a fundamental prerequisite for human endurance at all times. However, conventional single-purpose thermoregulatory materials frequently lack highly efficient integrated strategies to cope with diverse environmental demands. Here, an interface-confined assembly strategy that leverages interfacial rheology is developed to synthesize a carbon nanofiber metafabric with a hollow aerogel architecture for high-efficiency thermoregulation. By manipulating the interfacial viscosity gradient to suppress the inward radial diffusion of the sheath layer, phase separation within the shell layer is confined to an extremely thin thickness. Subsequently, the metafabric is obtained following the synchronized hierarchical pores evolution through preoxidation and optimized graphitization. With an ultrathin thickness of only 85 μm, the resulting metafabric exhibits efficient electrothermal capability (adjustable from 28 to 163 °C), photothermal property (radiation raised temperature by 44 °C), and passive thermal insulation (surface temperature ≈4 °C closer to ambient than that of commercial cotton). Simultaneously, the metafabric retains robust bending flexibility (fracture-free under large-angle) and breathability (water vapor transmission rate ≈3.2 kg m-2 d-1), ensuring both durability and wearable comfort. This work provides rich possibilities to develop advanced carbon nanomaterials for thermoregulation, holding great potential for next-generation smart textiles, all-weather personal thermal management, and energy-efficient wearable electronics.

A pivotal hurdle in traumatic brain injury (TBI) therapy is the self-perpetuating cycle between neuroinflammation and oxidative stress. Concurrent targeting of both pathways offers a promising strategy to overcome the key limitation in current therapy. Herein, a programmed streptavidin-condensed bifunctional nucleic acid nanoplatform (DZ-G4/H NPs) was developed via rolling circle amplification (RCA) to integrate numerous C1qa-cleaving DNAzymes with the peroxidase-like G-quadruplex/hemin (G4/H) complex. The platform ingeniously enhances the stability and drug-loading capacity of nucleic acid structures, enabling improved therapeutic efficacy through disruption of the self-perpetuating inflammation-oxidative stress cycle, which is superior to individual monotherapies. Consequently, it alleviated key pathophysiological hallmarks such as brain edema and cerebral blood flow (CBF) deficits, promoted holistic recovery of motor and cognitive functions, and ultimately improved survival in TBI mice. Beyond its promising application in TBI therapy that consolidates multiple therapeutic advantages, this nanostrategy offers a versatile method for streamlined programmed assembly of multifunctional modules, thereby providing an adaptable technical platform for the design and development of multifunctional nucleic acid drugs.

Triple-negative breast cancer (TNBC) remains a therapeutic challenge due to its aggressive behavior and lack of targeted treatments. We developed Sor@AKAExo, a bioinspired exosomic nanoplatform that utilizes Anoectochilus roxburghii-derived exosomes both as a nanotherapeutic delivering endogenous miRNAs and as a carrier for incorporating and delivering ferroptosis inducer sorafenib. Functionalization with the AS1411 aptamer enables tumor targeting, while conjugation with the KLA peptide facilitates mitochondrial localization, achieving spatiotemporal codelivery of both miRNAs and sorafenib. Accordingly, Sor@AKAExo synergistically induces ferroptosis and apoptosis through sorafenib-induced GPX4 suppression, lipid peroxidation, mitochondrial dysfunction, and caspase-3 activation. These effects are further enhanced by exosomal miRNA-mediated downregulation of the MAPK pathway and upregulation of the IL-17 and cholesterol metabolism pathways. This dual death-initiating mechanism disrupts the redox homeostasis, overcomes metabolic resistance, and remodels the immunosuppressive tumor microenvironment. In vivo, Sor@AKAExo exhibits potent antitumor efficacy with excellent biosafety. This work presents a bioinspired plant-derived exosome-based immunotherapy that synergistically activates both ferroptosis and apoptosis circuits with precise spatiotemporal control, addressing the obstacles of absent active targeting, limited drug delivery efficacy, and adaptive drug resistance in TNBC treatment.