Red light-induced localized release of carbon monoxide for alleviating postoperative cognitive dysfunction.

Inflammation within the central nervous system (CNS), which may be triggered by surgical trauma, has been implicated as a significant factor contributing to postoperative cognitive dysfunction (POCD). The relationship between mitigating inflammation at peripheral surgical sites and its potential to attenuate the CNS inflammatory response, thereby easing POCD symptoms, remains uncertain. Notably, carbon monoxide (CO), a gasotransmitter, exhibits pronounced anti-inflammatory effects. Herein, we have developed carbon monoxide-releasing micelles (CORMs), a nanoparticle that safely and locally liberates CO upon exposure to 650 nm light irradiation. In a POCD mouse model, treatment with CORMs activated by light (CORMs + hv) markedly reduced the concentrations of interleukin (IL)-6, IL-1ß, and tumor necrosis factor-alpha (TNF-α) in both the peripheral blood and the hippocampus, alongside a decrease in ionized calcium-binding adapter molecule 1 in the hippocampal CA1 region. Furthermore, CORMs + hv treatment diminished Evans blue extravasation, augmented the expression of tight junction proteins zonula occludens-1 and occludin, enhanced neurocognitive functions, and fostered fracture healing. Bioinformatics analysis and experimental validation has identified Htr1b and Trhr as potential key regulators in the neuroactive ligand-receptor interaction signaling pathway implicated in POCD. This work offers new perspectives on the mechanisms driving POCD and avenues for therapeutic intervention.

Single-Component High-Resolution Dual-Tone EUV Photoresists Based on Precision Self-Immolative Polymers.

Electron beam (EB) and extreme ultraviolet (EUV) lithography are advanced techniques capable of achieving sub-10 nm resolutions, critical for fabricating next-generation nanostructures and semiconductor devices. However, developing EUV photoresists that meet all demands for resolution, line edge roughness (LER), and sensitivity (RLS) remains a significant challenge. Herein, we introduce high-performance photoresists based on single-component self-immolative polymers (SIPs) with inherent signal amplification via cascade degradation. These SIPs function as dual-tone photoresists under both EB and EUV lithography, with performance primarily determined by the exposure dose. Lithographic evaluations show that discrete SIPs provide significant improvements over disperse counterparts, achieving higher resolution and reduced LER. Specifically, a discrete SIP with a DP of 12 produces a line-space pattern with a resolution of approximately 18 nm and an LER of 1.8 nm, compared to 21 nm resolution and 2.5 nm LER for disperse SIPs. Additionally, these SIP-based photoresists, enriched with aromatic structures, exhibit excellent etch resistance. The single-component nature and potential to address the RLS trade-off underscore the promise of discrete SIPs for EUV lithography.

Efficient Encapsulation of ß-Lapachone into Self-Immolative Polymer Nanoparticles for Cyclic Amplification of Intracellular Reactive Oxygen Species Stress.

The selective upregulation of intracellular oxidative stress in cancer cells presents a promising approach for effective cancer treatment. In this study, we report the integration of enzyme catalytic amplification and chemical amplification reactions in ß-lapachone (Lap)-loaded micellar nanoparticles (NPs), which are self-assembled from reactive oxygen species (ROS)-responsive self-immolative polymers (SIPs). This integration enables cyclic amplification of intracellular oxidative stress in cancer cells. Specifically, we have developed ROS-responsive SIPs with phenylboronic ester triggering motifs and hexafluoroisopropanol moieties in the side chains, significantly enhancing Lap loading efficiency (98%) and loading capacity (33%) through multiple noncovalent interactions. Upon ROS activation in tumor cells, the Lap-loaded micellar NPs disassemble, releasing Lap and generating additional ROS via enzyme catalytic amplification. This process elevates intracellular oxidative stress and triggers polymer depolymerization in a positive feedback loop. Furthermore, the degradation of SIPs via chemical amplification produces azaquinone methide intermediates, which consume intracellular thiol-related substrates, disrupt intracellular redox hemostasis, further intensify oxidative stress, and promote cancer cell apoptosis. This work introduces a strategy to enhance intracellular oxidative stress by combining enzymatic and chemical amplification reactions, providing a potential pathway for the development of highly efficient anticancer agents.

Advancing Artificial Cells with Functional Compartmentalized Polymeric Systems - In Honor of Wolfgang Meier.

The fundamental building block of living organisms is the cell, which is the universal biological base of all living entities. This micrometric mass of cytoplasm and the membrane border have fascinated scientists due to the highly complex and multicompartmentalized structure. This specific organization enables numerous metabolic reactions to occur simultaneously and in segregated spaces, without disturbing each other, but with a promotion of inter- and intracellular communication of biomolecules. At present, artificial nano- and microcompartments, whether as single components or self-organized in multicompartment architectures, hold significant value in the study of life development and advanced functional materials and in the fabrication of molecular devices for medical applications. These artificial compartments also possess the properties to encapsulate, protect, and control the release of bio(macro)molecules through selective transport processes, and they are capable of embedding or being connected with other types of compartments. The self-assembly mechanism of specific synthetic compartments and thus the fabrication of a simulated organelle membrane are some of the major aspects to gain insight. Considerable efforts have now been devoted to design various nano- and microcompartments and understand their functionality for precise control over properties. Of particular interest is the use of polymeric vesicles for communication in synthetic cells and colloidal systems to reinitiate chemical and biological communication and thus close the gap toward biological functions. Multicompartment systems can now be effectively created with a high level of hierarchical control. In this way, these structures can not only be explored to deepen our understanding of the functional organization of living cells, but also pave the way for many more exciting developments in the biomedical field.

Femtosecond laser direct nanolithography of perovskite hydration for temporally programmable holograms.

Modern nanofabrication technologies have propelled significant advancement of high-resolution and optically thin holograms. However, it remains a long-standing challenge to tune the complex hologram patterns at the nanoscale for temporal light field control. Here, we report femtosecond laser direct lithography of perovskites with nanoscale feature size and pixel-level temporal dynamics control for temporally programmable holograms. Specifically, under tightly focused laser irradiation, the organic molecules of layered perovskites (PEA)2PbI4 can be exfoliated with nanometric thickness precision and subwavelength lateral size. This creates inorganic lead halide capping nanostructures that retard perovskite hydration, enabling tunable hydration time constant. Leveraging advanced inverse design methods, temporal holograms in which multiple independent images are multiplexed with low cross talk are demonstrated. Furthermore, cascaded holograms are constructed to form temporally holographic neural networks with programmable optical inference functionality. Our work opens up new opportunities for tunable photonic devices with broad impacts on holography display and storage, high-dimensional optical encryption and artificial intelligence.

Two new saponins from the rhizomes of Paris yunnanensis Franch.

The phytochemical investigation on the rhizomes of Paris yunnanensis Franch. resulted in the discovery and characterisation of six compounds, including two new saponins named parisyunnanosides M-N (1-2), and four known ones (3-6). The structures of isolated compounds were determined by spectroscopic data analysis and chemical methods. Compound 2 is a pregnane-type saponin with a special α,ß-unsaturated carboxylic acid moiety at C-17, which is first discovered in genus Paris. The anti-inflammatory activity of the isolated compounds was assessed in vitro. The results demonstrated that compounds 3 and 4 could significantly inhibit the production of NO which was induced by LPS in RAW 264.7 cells with IC50 values of 0.67 ± 0.17 µM and 0.85 ± 0.12 µM, respectively.

Biomimetic Activation of N-Nitrosamides with Red Light-Triggered Nitric Oxide Release via Mediated Electron Transfer.

Mediated electron transfer (MET) is fundamental to many biological functions, including cellular respiration, photosynthesis, and enzymatic catalysis. However, leveraging the MET process to enable the release of therapeutic gases has been largely unexplored. Herein, we report the bio-inspired activation of a series of UV-absorbing N-nitrosamide derivatives (NOA) under red light exposure, enabling the quantitative release of nitric oxide (NO) gasotransmitter via an MET process. The cornerstone of our design is the covalent linkage of a 2,4-dinitroaniline moiety, which acts as an electron mediator to the N-nitrosamide groups. This facilitates efficient electron transfer from the excited palladium(II) meso-tetraphenyltetrabenzoporphyrin (PdTPTBP) photocatalyst and the selective activation of NOA. Our approach has been validated with distinct photocatalysts and various N-nitrosamides, including those derived from carbamates, amides, and ureas. Notably, the modulation of the linker length between the electron mediator and N-nitrosamide groups serves as a regulatory mechanism for controlling NO release kinetics. Moreover, this biomimetic NO release platform demonstrates effective operation under both normoxic and hypoxic conditions, and it enables localized delivery of NO under physiological conditions, exhibiting significant anticancer efficacy within the phototherapeutic window and enhanced selectivity towards tumor cells.

Advanced Synthesis, Structural Characterization, and Functional Applications of Precision Polymers.

In the realm of biological macromolecules, entities such as nucleic acids and proteins are distinguished by their homochirality, consistently defined chain lengths, and integral sequence-dependent functionalities. Historically, these refined attributes have eluded traditional synthetic polymers, which often exhibit wide variabilities in chain lengths, limited batch-to-batch reproducibility, and stochastic monomer arrangements. Bridging this divide represents a pivotal challenge within the domain of polymer science-a challenge that the burgeoning discipline of precision polymer chemistry is poised to address. Recent advancements have yielded precision polymers that boast prescribed monomer sequences and narrow molecular weight distributions, heralding a new era for developing model systems to decipher structure-property correlations within functional polymers, analogous to those within biological matrices. This review discusses the innovative liquid-phase and solid-phase synthesis techniques for creating precision polymers and the advanced characterization tools essential for dissecting their structure and properties. We highlight potential applications in self-assembly, catalysis, data storage, imaging, and therapy, and provide insights into the future challenges and directions of precision polymers.

Controlled switching thiocarbonylthio end-groups enables interconvertible radical and cationic single-unit monomer insertions and RAFT polymerizations.

To emulate the ordered arrangement of monomer units found in natural macromolecules, single-unit monomer insertion (SUMI) have emerged as a potent technique for synthesizing sequence-controlled vinyl polymers. Specifically, numerous applications necessitate vinyl polymers encompassing both radically and cationically polymerizable monomers, posing a formidable challenge due to the distinct thiocarbonylthio end-groups required for efficient control over radical and cationic SUMIs. Herein, we present a breakthrough in the form of interconvertible radical and cationic SUMIs achieved through the manipulation of thiocarbonylthio end-groups. The transition from a trithiocarbonate (for radical SUMI) to a dithiocarbamate (for cationic SUMI) is successfully accomplished via a radical-promoted reaction with bis(thiocarbonyl) disulfide. Conversely, the reverse transformation utilizes the reaction between dithiocarbamate and bistrithiocarbonate disulfide under a cationic mechanism. Employing this strategy, we demonstrate a series of synthetic examples featuring discrete oligomers containing acrylate, maleimide, vinyl ether, and styrene, compositions unattainable through the SUMI of a single mechanism alone.

Impact of dietary supplementation with ß-alanine on the rumen microbial crude protein supply, nutrient digestibility and nitrogen retention in beef steers elucidated through sequencing the rumen bacterial community.

This study investigated the effects of ß-alanine (ß-Ala) on rumen fermentation, nutrient digestibility, nitrogen (N) metabolism, plasma biochemical parameters, and rumen bacterial communities in beef steers. Six steers with initial liveweight of 252.8 ± 5.2 kg and 3 treatments of supplementing with 0, 30, or 60 g ß-Ala per day to basal diet were allocated in a replicated 3 × 3 Latin square design. Each experimental period was 20 d, of which the first 15 d were for adaptation and the subsequent 5 d were for sampling. The results showed that ß-Ala linearly increased the ruminal concentration of microbial crude protein (MCP) (P = 0.005), but it did not affect the ruminal concentrations of ammonia N and total volatile fatty acids (P > 0.10). ß-Ala also linearly increased the dry matter (DM) (P = 0.009), organic matter (OM) (P = 0.017) and crude protein (CP) (P = 0.043) digestibility, tended to decrease the acid detergent fiber digestibility (P = 0.077), but it did not affect the neutral detergent fiber digestibility (P = 0.641). ß-Ala quadratically increased the relative abundance of ruminal Bacteroidota (P = 0.021) at the phylum level, and increased Prevotella (P = 0.028) and Prevotellaceae_UCG-003 (P = 0.014), and decreased the relative abundance of NK4A214_group (P = 0.009) at the genus level. Feeding steers with ß-Ala linearly increased the urinary N (P = 0.006), urea excretions (P = 0.002) and the N retention (P = 0.004), but it did not affect the N utilization efficiency (P = 0.120). ß-Ala quadratically increased the plasma concentration of the total antioxidant capacity (P = 0.011) and linearly increased the plasma concentration of insulin-like growth factor-1 (P < 0.001). In summary, dietary supplementation with ß-Ala improved the rumen MCP supply and increased the digestibility of DM, OM, CP and the N retention. Further research is necessary to verify the ruminal degradability of ß-Ala and to investigate the mechanism of the impact of absorbed ß-Ala on the anti-oxidative ability in steers.

Dental Caries Management with Antibacterial Silver-Doped Prussian Blue Hydrogel by the Combined Effects of Photothermal Response and Ion Discharge.

Caries is a destructive condition caused by bacterial infection that affects the hard tissues of the teeth, significantly reducing the quality of life for individuals. Photothermal therapy (PTT) offers a noninvasive and painless treatment for caries, but the use of unsafe laser irradiance limits its application. To address this challenge, we prepared nanoparticles of silver ion-doped Prussian blue (AgPB), which was encased within cationic guar gum (CG) to form the antibacterial PTT hydrogel CG-AgPB with a photothermal conversion efficiency of 34.4%. When exposed to an 808 nm laser at a power density of 0.4 W/cm2, the hydrogel readily reached a temperature of over 50 °C in just 3 min, synchronized by the discharge of Ag+ ions from the interstitial sites of AgPB crystals, resulting in broad-spectrum and synergistic antibacterial activities (>99%) against individual oral pathogens (Streptococcus sanguinis, Streptococcus mutans, and Streptococcus sobrinus) and pathogen-induced biofilms. In vivo, CG-AgPB-mediated PTT demonstrated a capability to profoundly reduce the terminal number of cariogenic bacteria to below 1% in a rat model of caries. Given the outstanding biocompatibility, injectability, and flushability, this CG-AgPB hydrogel may hold promise as a next-generation oral hygiene adjunct for caries management in a clinical setting.

Inhibition of esophageal cancer progression through HACE1-TRIP12 interaction and associated RAC1 ubiquitination and degradation.

Objective: This study investigated the significance of HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) in esophageal cancer (ESCA) and its underlying mechanism in ESCA regulation through the induction of RAC1 ubiquitination and degradation. Methods: Characterization studies of HACE1 in ESCA clinical tissues and cell lines were performed. Next, the effects of HACE1 on the biological behavior of ESCA cells were examined by silencing and overexpressing HACE1. Protein-protein interactions (PPIs) involving HACE1 were analyzed using data from the String website. The function of HACE1 in RAC1 protein ubiquitination was validated using the proteasome inhibitor MG132. The effects of HACE1 on ESCA cells through RAC1 were elucidated by applying the RAC1 inhibitor EHop-016 in a tumor-bearing nude mouse model. To establish the relationship between HACE1 and TRIP12, rescue experiments were conducted, mainly to evaluate the effect of TRIP12 silencing on HACE1-mediated RAC1 regulation in vitro and in vivo. The PPI between HACE1 and TRIP12 and their subcellular localization were further characterized through co-immunoprecipitation and immunofluorescence staining assays, respectively. Results: HACE1 protein expression was notably diminished in ESCA cells but upregulated in normal tissues. HACE1 overexpression inhibited the malignant biological behavior of ESCA cells, leading to restrained tumor growth in mice. This effect was coupled with the promotion of RAC1 protein ubiquitination and subsequent degradation. Conversely, silencing HACE1 exhibited contrasting results. PPI existed between HACE1 and TRIP12, compounded by their similar subcellular localization. Intriguingly, TRIP12 inhibition blocked HACE1-driven RAC1 ubiquitination and mitigated the inhibitory effects of HACE1 on ESCA cells, alleviating tumor growth in the tumor-bearing nude mouse model. Conclusion: HACE1 expression was downregulated in ESCA cells, suggesting that it curbs ESCA progression by inducing RAC1 protein degradation through TRIP12-mediated ubiquitination.

Codelivery of Gaseous Signaling Molecules for Biomedical Applications.

Gaseous signaling molecules (GSMs) including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) have presented excellent therapeutic efficacy such as anti-inflammatory, anti-microbial and anti-cancer effects and multiple biomedical applications in recent years. As the three most vital signaling molecules in human physiology, these three GSMs show so intertwined and orchestrated interactions that the synergy of multiple gases may demonstrate a more complex therapeutic potential than single gas delivery. Consequently, researchers have been devoted to developing codelivery systems of GSMs by synthesizing a single molecule as a dual donor to maximize the gaseous therapeutic efficacy. In this minireview, we summarize the recent developments of molecules or materials enabling codelivery of GSMs for biomedical applications. It appears that compared with the abundant cases of codelivery of NO and H2S, research on codelivery of CO and the other two GSMs separately remains to be explored.

Scale-Up Preparation of Manganese-Iron Prussian Blue Nanozymes as Potent Oral Nanomedicines for Acute Ulcerative Colitis.

Prussian blue (PB) nanozymes are demonstrated as effective therapeutics for ulcerative colitis (UC), yet an unmet practical challenge remains in the scalable production of these nanozymes and uncertainty over their efficacy. With a novel approach, a series of porous manganese-iron PB (MnPB) colloids, which are shown to be efficient scavengers for reactive oxygen species (ROS) including hydroxyl radical, superoxide anion, and hydrogen peroxide, are prepared. In vitro cellular experiments confirm the capability of the nanozyme to protect cells from ROS attack. In vivo, the administration of MnPB nanozyme through gavage at a dosage of 10 mg kg-1 per day for three doses in total potently ameliorates the pathological symptoms of acute UC in a murine model, resulting in mitigated inflammatory responses and improved viability rate. Significantly, the nanozyme produced at a large scale can be achieved at an unprecedented yield weighting ≈11 g per batch of reaction, demonstrating comparable anti-ROS activities and treatment efficacy to its small-scale counterpart. This work represents the first demonstration of the scale-up preparation of PB analog nanozymes for UC without compromising treatment efficacy, laying the foundation for further testing of these nanozymes on larger animals and promising clinical translation.

Coupling effect of key factors on ecosystem services in border areas: a study of the Pu'er region, Southwestern China.

The coupling effects created by transboundary and local factors on ecosystem services are often difficult to determine. This poses great challenges for ecosystem protection and management in border areas. To decrease uncertainty, it is crucial to quantify and spatialize the impact multiple factors have on ecosystem services within different scenarios. In this study, we identified key transboundary and local factors from a set of 15 sorted factors related to four main ecosystem services. We employed a Bayesian Network-Geographic Information System (BN-GIS) model to simulate 90 scenarios with multiple factors combinations, quantifying and spatializing the coupling effects on the main ecosystem services. These simulations were conducted in the Pu'er region, which is situated alongside three countries, and serves as a representative border area in southwest China. The results showed that: (1) The coupling effects of multiple factors yield significant variations when combined in different scenarios. Managers can optimize ecosystem services by strategically regulating factors within specific areas through the acquisition of various probabilistic distributions and combinations of key factors in positive coupling effect scenarios. The outcome is a positive coupling effect. (2) Among the four main ecosystem services in the Pu'er region, food availability and biodiversity were affected by key transboundary and local factors. This suggests that the coupling of transboundary and local factors is more likely to have a significant impact on these two ecosystem services. Of the 45 combination scenarios on food availability, the majority exhibit a negative coupling effect. In contrast, among the 45 combination scenarios on biodiversity, most scenarios have a positive coupling effect. This indicates that food availability is at a higher risk of being influenced by the coupling effects of multiple factors, while biodiversity faces a lower risk. (3) Transboundary pests & diseases, application of pesticides, fertilizer & filming , population density, and land use were the key factors affecting food availability. Bio-invasion, the normalized differential vegetation index, precipitation, and the landscape contagion index were the key factors affecting biodiversity. In this case, focusing on preventing transboundary factors such as transboundary pests & disease and bio-invasion should be the goal. (4) Attention should also be paid to the conditions under which these transboundary factors combine with local factors. In the areas where these negative coupling effects occur, enhanced monitoring of both transboundary and local factors is essential to prevent adverse effects.

Mechanism of effect of stenting on hemodynamics at iliac vein bifurcation.

When performing stent intervention for iliac vein compression syndrome, the operator selects the appropriate stent and determines its implantation depth according to the type and severity of iliac vein stenosis in the patient. However, there is still uncertainty regarding how the structure of the stent and its implantation depth affect hemodynamics at the site of lesion. In this paper, we analyzed three commonly used stents (Vena stent from Venmedtch, Venovo from Bard, and Smart stent from Cordis) with different implantation depths (0, 10, 20 mm) using computational fluid dynamics (CFD). We focused on evaluating hemorheological parameters such as time-averaged wall shear stress (TAWSS), oscillatory shear index (OSI), etc., within one pulsatile cycle after stent implantation. The correlation between geometric parameters of the stents and hemodynamic indicators was assessed using Pearson correlation coefficient (r), which was further validated through PIV velocity measurement experiment. The results revealed that an increase in implantation depth led to a more pronounced disturbance effect on blood flow at bifurcation for densely arranged support body-type stents. This effect was particularly significant during periods of smooth blood flow. On the other hand, crown-shaped Vena stents exhibited relatively less disruption to blood flow post-implantation. Implantation depth showed a strong negative correlation with TAWSS but a strong positive correlation with OSI and RRT. These findings suggest an increased risk of thrombosis at iliac vein bifurcation following stent placement. Amongst all three tested stents, Vena Stent demonstrated more favorable periodic parameters after implantation compared to others. These results provide valuable theoretical insights into understanding contralateral circulation thrombosis associated with iliac vein stenting.

Engineering Semicarbazide-Bearing Polypeptide Conjugates for Efficient Tumor Chemotherapy and Imaging of Tumor Metastasis.

Polypeptide materials offer scalability, biocompatibility, and biodegradability, rendering them an ideal platform for biomedical applications. However, the preparation of polypeptides with specific functional groups, such as semicarbazide moieties, remains challenging. This work reports, for the first time, the straightforward synthesis of well-defined methoxy-terminated poly(ethylene glycol)-b-polypeptide hybrid block copolymers (HBCPs) containing semicarbazide moieties. This synthesis involves implementing the direct polymerization of environment-stable N-phenoxycarbonyl-functionalized α-amino acid (NPCA) precursors, thereby avoiding the handling of labile N-carboxyanhydride (NCA) monomers. The resulting HBCPs containing semicarbazide moieties enable facile functionalization with aldehyde/ketone derivatives, forming pH-cleavable semicarbazone linkages for tailored drug release. Particularly, the intracellular pH-triggered hydrolysis of semicarbazone moieties restores the initial semicarbazide residues, facilitating endo-lysosomal escape and thus improving therapeutic outcomes. Furthermore, the integration of the hypoxic probe (Ir(btpna)(bpy)2 ) into the pH-responsive nanomedicines allows sequential responses to acidic and hypoxic tumor microenvironments, enabling precise detection of metastatic tumors. The innovative approach for designing bespoke functional polypeptides holds promise for advanced drug delivery and precision therapeutics.

A Single-Component Dual Donor Enables Ultrasound-Triggered Co-release of Carbon Monoxide and Hydrogen Sulfide.

The development of dual gasotransmitter donors can not only provide robust tools to investigate their subtle interplay under pathophysiological conditions but also optimize therapeutic efficacy. While conventional strategies are heavily dependent on multicomponent donors, we herein report an ultrasound-responsive water-soluble copolymer (PSHF) capable of releasing carbon monoxide (CO) and hydrogen sulfide (H2 S) based on single-component sulfur-substituted 3-hydroxyflavone (SHF) derivatives. Interestingly, sulfur substitution can not only greatly improve the ultrasound sensitivity but also enable the co-release of CO/H2 S under mild ultrasound irradiation. The co-release of CO/H2 S gasotransmitters exerts a bactericidal effect against Staphylococcus aureus and demonstrates anti-inflammatory activity in lipopolysaccharide-challenged macrophages. Moreover, the excellent tissue penetration of ultrasound irradiation enables the local release of CO/H2 S in the joints of septic arthritis rats, exhibiting superior therapeutic efficacy without the need for any antibiotics.

Biofilm heterogeneity-adaptive photoredox catalysis enables red light-triggered nitric oxide release for combating drug-resistant infections.

The formation of biofilms is closely associated with persistent and chronic infections, and physiological heterogeneity such as pH and oxygen gradients renders biofilms highly resistant to conventional antibiotics. To date, effectively treating biofilm infections remains a significant challenge. Herein, we report the fabrication of micellar nanoparticles adapted to heterogeneous biofilm microenvironments, enabling nitric oxide (NO) release through two distinct photoredox catalysis mechanisms. The key design feature involves the use of tertiary amine (TA) moieties, which function as sacrificial agents to avoid the quenching of photocatalysts under normoxic and neutral pH conditions and proton acceptors at acidic pH to allow deep biofilm penetration. This biofilm-adaptive NO-releasing platform shows excellent antibiofilm activity against ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) biofilms both in vitro and in a mouse skin infection model, providing a strategy for combating biofilm heterogeneity and biofilm-related infections.

Label-Free Quantification of Digital Nanorods Assembled from Discrete Oligourethane Amphiphiles.

Polymeric nanoparticles (NPs) have been extensively designed for theranostic agent delivery. Previous methods for tracking their biological behavior and assessing theranostic efficacy heavily rely on fluorescence or isotope labeling. However, these labeling techniques may alter the physicochemical properties of the labeled NPs, leading to inaccurate biodistribution information. Therefore, it is highly desirable to develop label-free techniques for accurately assessing the biological fate of polymeric NPs. Here, we create discrete oligourethane amphiphiles (DOAs) with methoxy (OMe), hydroxyl (OH), and maleimide (MI) moieties at the dendritic oligo(ethylene glycol) (dOEG) ends. We obtained four types of digital nanorods (NRs) with distinct surface functional groups through self-assembly of a single DOA (OMe and OH NRs) or coassembly of two DOAs (OMe-MI and OH-MI NRs). These unique NRs can be directly quantified in a label-free manner by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Specifically, OMe-MI NRs exhibited the best blood circulation, and OH-MI showed the highest area under the curve (AUC) value after intravenous injection. Biodistribution studies demonstrated that MI-containing NRs generally had lower accumulation in the liver and spleen compared to that of MI-free NRs, except for the comparison between OMe and OMe-MI NRs in the liver. Proteomics studies unveiled the formation of distinct protein coronas that may greatly affect the biological behavior of NRs. This study not only provides a label-free technique for quantifying the pharmacokinetics and biodistribution of polymeric NRs but also highlights the significant impact of surface functional groups on the biological fate of polymeric NPs.