A novel biomimetic and redox-responsive hybrid lipid polymer nanoparticle for targeting sepsis microenvironment and modulating inflammation.

Stimuli-responsive logical gate biosensor based on integrated DNAzyme probe for the discrimination of cancer cells.

Ion storage in a quadrupole linear ion trap (QLIT) in the x- and y-dimensions relies on a quadrupolar electric field that oscillates at a radio-frequency. In the z-dimension, trapping can take place either via a fixed DC electrostatic potential, via oscillatory AC voltages, or via a combination of the two applied to plates situated at the ends of the QLIT. With a combination of an AC barrier with an attractive DC potential, it is possible to effect storage in the z-dimension that is mass-to-charge (m/z) dependent. In this work, the m/z-dependent release of ions from a QLIT to an adjacent time-of-flight (TOF) mass spectrometer is demonstrated. An application of this phenomenon is demonstrated with gas-phase ion/ion proton transfer reactions in which high m/z ions generated via charge-state reduction are released to a TOF mass analyzer before a significant degree of neutralization can take place. The transfer of a product ion from a QLIT to an adjacent mass analyzer is referred to as 'valet parking'. Valet parking has been demonstrated previously using ion/molecule proton transfer reactions with the transfer of ions within a narrow band of m/z values. The selective release of ions that exceed a threshold m/z value allows for the simultaneous valet parking of ions derived from mixtures of analytes. This is referred to a 'parallel valet parking', which is demonstrated here with a three-protein mixture of cytochrome c, ubiquitin, and myoglobin.

Osteosarcoma (OS) remains the most prevalent malignant bone tumor, with stagnant survival rates and high recurrence risk due to residual tumor cells, and limited post-resection bone regeneration. Existing bifunctional bone graft substitutes integrating anticancer activity with osteogenesis are hindered by uncontrolled drug release and inefficient intracellular delivery. Here, we report a pH-sensitive nano-microparticle linking strategy, in which imine bonds are used as interfacial linkers between therapeutic nanoparticles and bone scaffolds to enable tumor microenvironment-triggered, on-demand nanotherapeutic release. In this study, we develop β-tricalcium phosphate (β-TCP) granules decorated with selenium (Se)-doped mesoporous silica nanoparticles (SeMIA@TCP), in which nanoparticles are functionalized with imine bonds for acidic pH-responsive detachment and alendronate for strong β-TCP binding. This design ensures stable nanoparticle immobilization under physiological conditions while enabling selective release within the mildly acidic OS microenvironment. In vitro, the SeMIA@TCP showed significant pH-dependent cytotoxicity toward OS cells, while maintaining low toxicity toward human mesenchymal stem cells (hMSCs) under physiological conditions, indicating a OS-targeting profile. Furthermore, the released nanoparticles enhanced alkaline phosphatase (ALP) expression and mineralization in hMSCs, underscoring their osteogenic potential. Collectively, these results demonstrate the potential of tumor microenvironment-responsive Se-doped MSN-assembled TCP granules as a design platform for bifunctional scaffolds in bone cancer treatment.

Transthyretin (TTR) is a tetrameric protein present in plasma and cerebrospinal fluid that binds to thyroxine (T4) and retinol (vitamin A) to transport them across the blood-retina barrier and to the liver. Mutations on the TTR gene cause destabilization of the tetramer structure leading to misfolded monomers and aggregates, thus triggering several pathologies (i.e., cardiomyopathy and neurodegeneration). The stabilization of TTR tetramer architecture and the silencing of TTR gene expression represent viable therapeutic strategies for amyloidosis. Moreover, the TTR role as a delivery system using drug (bio)conjugates has increasingly been interrogated over the last years to facilitate the transport of different drugs displaying poor pharmacokinetic properties. In this Perspective, we highlight TTR two-faced features as a drug target and carrier, reporting the latest findings in TTR stabilization and its involvement as a drug carrier for the selective drug release on different receptors and cells, thus providing insights for future medicinal chemistry applications.

Precise discrimination between protein abundance and catalytic activity of proteases remains a critical yet challenging objective in biomedical diagnostics due to overlapping biological functions, intricate regulatory mechanisms, and extensive interference from endogenous biomolecules. Herein, we report a novel dual-lock DNA biosensing platform, exemplified through myeloperoxidase (MPO), which concurrently integrates aptamer-mediated molecular recognition and hypochlorous acid (HOCl)-triggered oxidative cleavage to rigorously assess both MPO protein expression and enzymatic functionality. Specifically, MPO interaction with a conformationally structured DNA aptamer facilitates selective release of a trigger strand, while HOCl, produced enzymatically by active MPO, cleaves a strategically phosphorothioate-modified hairpin structure. Only upon simultaneous fulfillment of these two molecular conditions does the sensing mechanism activate a downstream catalytic hairpin assembly (CHA), achieving significant signal amplification. This stringent AND logic gate configuration markedly suppresses false positives and nonspecific background signals, demonstrating exceptional reliability across diverse and complex biological samples including serum, saliva, and cellular lysates. The proposed biosensing strategy thus provides a versatile, accurate, and broadly applicable analytical tool for simultaneous quantification of protease content and functional activity, holding considerable promise for advancing clinical diagnostics and pathological investigations.

Photoresponsive and UCST-Type thermoresponsive block Copolymer-Based composite micelles for Dual-Stimuli-Triggered selective and programmable release

Albumin is a promising vehicle for anticancer drug delivery due to its high plasma concentration, long half-life and known tumor accumulation. Drugs can be covalently conjugated to albumin via the free thiol at Cys34, using maleimide chemistry. Interestingly, such strategies have not yet been applied to tyrosine kinase inhibitors (TKIs), e.g. crucial in lung cancer treatment. This study investigates a prodrug delivery system for a derivative of the approved epidermal growth factor receptor (EGFR) inhibitor osimertinib, incorporating a maleimide for albumin binding and a cathepsin B-cleavable valine-citrulline (ValCit) dipeptide for selective drug release. In silico and in vitro studies confirmed the prodrug nature. Additionally, selective albumin-binding and efficient cathepsin B-mediated drug release were demonstrated. In non-small cell lung cancer (NSCLC) xenografts, the prodrug exhibited enhanced anticancer activity compared to osimertinib and a noncleavable glycine-glycine (GlyGly) control. These results highlight covalent albumin-binding as a promising strategy for TKI delivery.

Abstract Glioblastoma (GBM) is a very aggressive and invasive brain tumor that is difficult to treat due to its genetic variation, resistance to conventional treatment, and high recurrence. Even though there has been a great advancement in surgical, chemotherapy, and radiotherapy treatments, the poor prognosis for patients and low survival rates remain unchanged. Boron Neutron Capture Therapy (BNCT) is a new targeted treatment that offers precision with maximum efficacy while minimizing invasiveness. Through this process, the selective release of boron into the tumor cells was distributed to the tumor site. This review article discusses the mechanism of BNCT and its advantages and disadvantages, clinical research on BNCT in GBM patients, and their future aspects to manage glioblastoma. Overall, the review critically evaluates its reliability problems and future possibilities, emphasizing its potential to transform treatment results for this life-threatening condition.

Laser-assisted transfer printing has gained attention for integrating microdevices on unusual substrates. However, conventional technologies exhibit limited fault tolerance during laser-matter interactions, reducing transfer accuracy due to unavoidable irradiation deviations. We report a self-aligned laser transfer (SALT) that enables high-precision, programmable assembly of microchips without precise laser-to-die alignment. A thermal conductivity gradient carbon (TCGC), with an upper graphene layer and lower amorphous carbon layer, is embedded in the stamp via excimer laser self-limited carbonization of polyimide. The TCGC converts asymmetric light input into uniform heat output under non-uniform/misaligned infrared laser irradiation, whereas the upper graphene layer absorbs heat from the lower amorphous carbon and rapidly conducts heat laterally, ensuring uniform heat distribution of the underlying adhesive layer. This guarantees synchronous chip release at all adhesive sites, mitigating transfer deviations. Additionally, periodically arranged, grayscale-controlled TCGC can be fabricated by modulating excimer laser parameters during carbonization, thereby enabling selective microchip release without pre-planned scanning paths. SALT achieves excellent size compatibility ( < 100 micrometers) and high tolerance for irradiation deviations (transfer accuracy <5 micrometers). Demonstrations of RGB micro-LED display highlight its self-aligned and batch-selective capabilities.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by profound metabolic rewiring and a strongly immunosuppressive tumor microenvironment, both of which contribute to poor therapeutic responses. Immunogenic cell death (ICD) represents a potential strategy to overcome immune suppression by coupling tumor cell death to anti-tumor immune activation. Here, we investigated whether targeting amino acid metabolism in PDAC can induce ICD and promote tumor immunity. Through a focused metabolic screen in a panel of syngeneic mouse cancer cell lines, we identified cysteine restriction as a robust inducer of multiple damage-associated molecular patterns (DAMPs) in vitro, hallmark features of ICD. In addition to driving DAMPs, cystine-deprived tumor cells also promoted dendritic cell phagocytosis, maturation, and proinflammatory cytokine production in vitro. Because cysteine deprivation is a known trigger of ferroptosis, we further demonstrated that pharmacologic inhibition of glutathione peroxidase 4 (GPX4) similarly elicited ICD-associated features, which were reversible by the ferroptosis inhibitor Ferrostatin-1.To define additional immune-modulatory signals associated with ferroptosis, we performed metabolomic and lipidomic profiling of cells undergoing, but not yet committed to, ferroptotic death. These analyses revealed selective release of immunosuppressive metabolites and oxidized phospholipids. Consistent with this, conditioned media from ferroptotic cells impaired CD8+ T cell proliferation and cytotoxicity in vitro. Thus, together our results indicated that the induction of ferroptotic immunogenic cell death led to the release of both pro- and anti-inflammatory signals. Subsequent analysis in vivo revealed that ferroptotic tumor cells predominantly contributed to a tumor-protective environment. In particular, tumors inoculated with ferroptotic cells were enriched with immunosuppressive myeloid cells and exhibited reduced populations of tumor-infiltrating CD8+ T cells. Further investigation using immune compromised mice suggested that ferroptotic cells may suppress both adaptive and innate immune responses. Collectively, these results underscore the complex and highly context-dependent effects of ferroptosis on tumor immunity, highlighting the critical importance of in vivo models to determine true immunogenic potential within the tumor microenvironment.

Dual-photoresponsive substrates enabling light-induced single-cell patterning and sorting of nonadherent mammalian cells.

Due to the inherent defects of photodynamic therapy (PDT), its application in the treatment of deep-tissue metastatic tumors remains challenging. To extend the applicability of PDT, a novel chemiexcited photosensitizer, Cy7-EOM, was developed by covalently coupling the photosensitizer Cy7 with a peroxycatechol derivative and encapsulating it within folate-modified and disulfide-containing nano-micelles. Upon targeted delivery and selective release, positively charged Cy7-EOM would target the mitochondria and efficiently generate singlet oxygen (1O2) through intramolecular chemical energy transfer (ICET), directly inducing mitochondrial damage and cell apoptosis, realizing an efficient PDT for deep-tissue metastatic tumors. Remarkably, the covalent tethering of the photosensitizer to the peroxyoxalate ensures their spatial proximity to within 1 nm. This configuration profoundly boosts the efficiency of ICET, achieving potent PDT even at low endogenous levels of H2O2. Moreover, the tumor-specific decomposition of the nano-micelles eliminates the quenching effect caused by aggregation and removes the diffusion barrier to 1O2, while in normal tissues the integrity of the nano-micelles shields the tissues against the lethal effects of 1O2. This method provides a new strategy for transforming adjuvant photosensitizers into direct therapeutic drugs, with significant potential for clinical application in the treatment of metastatic tumors.

Development of PI3K/mTOR-HSP90 ligand conjugates for improved colorectal cancer therapy.

Spatiotemporal control of prodrug activation through external stimuli for effective and safe on-site release in solid tumors: From current advances to future perspectives.

Optimization of oxygen and hydrogen analysis in salts by inert gas fusion.

Oxidative dehydrogenation (ODHE) of C2H6 and CO2 to generate C2H4 and CO is industrially important but remains a long-standing challenge due to the complexity of this co-conversion and the thermodynamically stable and kinetically inert nature of both reactants. Herein, we theoretically demonstrated that the RhxNby- (x + y = 5) bimetallic clusters can drive the ODHE of C2H6 and CO2 to produce C2H4, CO, and H2O. The results indicated that the desorption of C2H4 and CO takes place under mild conditions, and the increased number of Rh atoms in RhxNby- leads to progressively more difficult C2H4 desorption. In contrast, the formation and evaporation of H2O represent the kinetically and thermodynamically demanding pathway to govern the overall efficiency of ODHE. This finding provides an integrated picture to understand the fundamental mechanisms of the ODHE of C2H6 and CO2. The selective release of C2H4 and the rate-determining behaviour of H2O generation were rationalized.

Bio-responsive self-assembled nanoparticles of fatty acid prodrugs of sulfapyridine for the management of Rheumatoid arthritis.

Droplet-based microfluidics enables miniaturized, high-throughput biochemical assays but faces challenges in selective droplet retrieval, particularly after long-term monitoring. While light-induced bubble generation offers a promising, hardware-simplified strategy for releasing individual droplets from passive traps, current implementations suffer from fabrication complexity or slow-release kinetics. To overcome these limitations, we previously developed a light-responsive fluorosurfactant using fluorinated plasmonic nanoparticles (f-PNPs) that enables millisecond-scale vapor bubble formation and efficient droplet release using a 532 nm laser, without requiring integrated photothermal materials. However, automation of this approach was limited by the need for manual droplet identification and release decisions. In this work, we introduce a fully automated Fluorescence-Activated Droplet Release (FADR) system by integrating the light-triggered release mechanism with a deep-learning-based droplet detector. This AI module autonomously identifies and localizes droplets in real-time, triggering selective release based on fluorescence intensity without human intervention. The closed-loop FADR platform offers a scalable and intelligent solution for precise droplet manipulation, enabling robust, high-throughput screening workflows with minimal hardware complexity.

Bacteria-targeted dual-lock delivery for closed-loop immune modulation in colorectal cancer.