Atomic Au3Cu Palisade Interlayer in Core@Shell Nanostructures for Efficient Kirkendall Effect Mediation.

Plasmonic Cu@semiconductor heteronanocrystals (HNCs) have many favorable properties, but the synthesis of solid structures is often hindered by the nanoscale Kirkendall effect. Herein, we present the use of an atomically thin Au3Cu palisade interlayer to reduce lattice mismatch and mediate the Kirkendall effect, enabling the successive topological synthesis of Cu@Au3Cu@Ag, Cu@Au3Cu@Ag2S, and further transformed solid Cu@Au3Cu@CdS core-shell HNCs via cation exchange. The atomically thin and intact Au3Cu palisade interlayer effectively modulates the diffusion kinetics of Cu atoms as demonstrated by experimental and theoretical investigations and simultaneously alleviates the lattice mismatch between Cu and Ag as well as Cu and CdS. The Cu@Au3Cu@CdS HNCs feature exceptional crystallinity and atomically organized heterointerfaces between the plasmonic metal and the semiconductor. This results in the efficient plasmon-induced injection of hot electrons from Cu@Au3Cu into the CdS shell, enabling the Cu@Au3Cu@CdS HNCs to achieve high activity and selectivity for the photocatalytic reduction of CO2 to CO.

McWRKY43 Confers Cold Stress Tolerance in Michelia crassipes via Regulation of Flavonoid Biosynthesis.

WRKY transcription factor (TF) plays a crucial role in plant abiotic stress response, but it is rarely reported in Michelia crassipes. Our studies have found that the transcription factor McWRKY43, a member of the IIc subgroup, is strongly upregulated under cold stress. In this study, we cloned the full length of McWRKY43 to further investigate the function of McWRKY43 in resistance to cold stress and its possible regulatory pathways in M. crassipes. Under cold stress, the seed-germination rate of transgenic tobacco was significantly higher than that of the wild type, and the flavonoid content, antioxidant enzyme activities, and proline content of transgenic tobacco seedlings were significantly increased, which promoted the expression of flavonoid pathway structural genes. In addition, the transient transformation of McWRKY43 in the M. crassipes leaves also found the accumulation of flavonoid content and the transcription level of flavonoid structural genes, especially McLDOX, were significantly increased under cold stress. Yeast one-hybrid (Y1H) assay showed that McWRKY43 could bind to McLDOX promoter, and the transcription expression of McLDOX was promoted by McWRKY43 during cold stress treatment. Overall, our results indicated that McWRKY43 is involved in flavonoid biosynthetic pathway to regulate cold stress tolerance of M. crassipes, providing a basis for molecular mechanism of stress resistance in Michelia.

Three-Component Donor-π-Acceptor Covalent-Organic Frameworks for Boosting Photocatalytic Hydrogen Evolution.

Two-dimensional covalent-organic frameworks (2D COFs) have recently emerged as great prospects for their applications as new photocatalytic platforms in solar-to-hydrogen conversion; nevertheless, their inefficient solar energy capture and fast charge recombination hinder the improvement of photocatalytic hydrogen production performance. Herein, two photoactive three-component donor-π-acceptor (TCDA) materials were constructed using a multicomponent synthesis strategy by introducing electron-deficient triazine and electron-rich benzotrithiophene moieties into frameworks through sp2 carbon and imine linkages, respectively. Compared with two-component COFs, the novel TCDA-COFs are more convenient in regulating the inherent photophysical properties, thereby realizing outstanding photocatalytic activity for hydrogen evolution from water. Remarkably, the first sp2 carbon-linked TCDA-COF displays an impressive hydrogen evolution rate of 70.8 ± 1.9 mmol g-1 h-1 with excellent reusability in the presence of 1 wt % Pt under visible-light illumination (420-780 nm). Utilizing the combination of diversified spectroscopy and theoretical prediction, we show that the full π-conjugated linkage not only effectively broadens the visible-light harvesting of COFs but also enhances charge transfer and separation efficiency.

Vertical Heterogeneous Integration of Metal Halide Perovskite Quantum-Wires/Nanowires for Flexible Narrowband Photodetectors.

Charge collection narrowing (CCN) has been reported to be an efficient strategy to achieve optical filter-free narrowband photodetection (NPD) with metal halide perovskite (MHP) single crystals. However, the necessity of utilizing thick crystals in CCN limits their applications in large scale, flexible, self-driven, and high-performance optoelectronics. Here, for the first time, we fabricate vertically integrated MHP quantum wire/nanowire (QW/NW) array based photodetectors in nanoengineered porous alumina membranes (PAMs) showing self-driven broadband photodetection (BPD) and NPD capability simultaneously. Two cutoff detection edges of the NPDs are located at around 770 and 730 nm, with a full-width at half-maxima (fwhm) of around 40 nm. The optical bandgap difference between the NWs and the QWs, in conjunction with the high carrier recombination rate in QWs, contributes to the intriguing NPD performance. Thanks to the excellent mechanical flexibility of the PAMs, a flexible NPD is demonstrated with respectable performance. Our work here opens a new pathway to design and engineer a nanostructured MHP for novel color selective and full color sensing devices.

Artificial stem cells mediated inflammation-tropic delivery of antiviral drugs for pneumonia treatment.

BACKGROUND: Cytomegalovirus (CMV) pneumonia is a major cause of morbidity and mortality in immunodeficiency individuals, including transplant recipients and Acquired Immune Deficiency Syndrome patients. Antiviral drugs ganciclovir (GCV) and phosphonoformate (PFA) are first-line agents for pneumonia caused by herpesvirus infection. However, the therapy suffers from various limitations such as low efficiency, drug resistance, toxicity, and lack of specificity. METHODS: The antiviral drugs GCV and PFA were loaded into the pH-responsive nanoparticles fabricated by poly(lactic-co-glycolic acid) (PLGA) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), and further coated with cell membranes derived from bone marrow mesenchymal stem cells to form artificial stem cells, namely MPDGP. We evaluated the viral suppression effects of MPDGP in vitro and in vivo. RESULTS: MPDGP showed significant inflammation tropism and efficient suppression of viral replication and virus infection-associated inflammation in the CMV-induced pneumonia model. The synergistic effects of the combination of viral DNA elongation inhibitor GCV and viral DNA polymerase inhibitor PFA on suppressing the inflammation efficiently. CONCLUSION: The present study develops a novel therapeutic intervention using artificial stem cells to deliver antiviral drugs at inflammatory sites, which shows great potential for the targeted treatment of pneumonia. To our best knowledge, we are the first to fabricate this kind of artificial stem cell to deliver antiviral drugs for pneumonia treatment.

Oral Administration of Starting Materials for In Vivo Synthesis of Antibacterial Gold Nanoparticles for Curing Remote Infections.

Oral administration is a facile and safe way for medication. However, most of the reported nanomedicines could not be taken orally, partially due to their unsatisfied stability, poor absorbance, or toxicity in the gastrointestinal tract. Here, we demonstrate that we could robustly synthesize gold nanoparticles (GNPs) in vivo by orally administering two starting materials, tetrachloroauric acid and aminophenyl boronic acid (ABA). The ABA-activated GNPs (A-GNPs) synthesized in vivo could be absorbed by the gastrointestinal tract and reach the remote infection lesions such as peritonitis caused by multidrug resistant (MDR) bacteria in mice. The A-GNPs exhibit excellent antibacterial efficacy (MIC, 3 µg/mL), long half-life (16-17 h), effective clearance (residual concentration is near 0 within 72 h), and high biosafety (safe dose/effective dose, 8 times). Our study is a pioneering attempt for synthesizing and taking nanomedicines orally just like preparing and drinking a cocktail.

The Density of Surface Coating Can Contribute to Different Antibacterial Activities of Gold Nanoparticles.

With the widespread use of antibiotics, the number of complex infection cases caused by unknown pathogens is increasing and novel antibiotics with tunable antibacterial spectra and low toxicity are highly desirable. Herein, we report that, by selecting thiol or amine, two groups with different binding affinities with gold, as anchoring groups, phenylboronic acid can be decorated on gold nanoparticles (AuNPs) with different densities, which contributes to Gram-selective antibacterial activities of the AuNPs. The AuNPs modified with amine- or thiol-tethered phenylboronic acids specifically bind to lipopolysaccharide (LPS, Gram-negative) or lipoteichoic acid (LTA, Gram-positive), respectively. By modifying AuNPs with different ratios of thiol- and amine-tethered phenylboronic acids, the resulting AuNPs show potent and tunable antibacterial activity. The AuNP-based antibacterial agents with optional Gram selectivity are promising for applications in personalized therapy.

Reversing the Chirality of Surface Ligands Can Improve the Biosafety and Pharmacokinetics of Cationic Gold Nanoclusters.

Severe toxicity and rapid in vivo clearance of cationic nanomaterials seriously hinder their clinical translation. Present strategies to improve the biosafety and in vivo performance of cationic nanomaterials require neutralization of positive charge, which often compromises their efficacy. Herein, we report that substituting L-glutathione (L-GSH) on cationic gold nanoclusters (GNCs) with its D-counterpart can effectively improve the biosafety and pharmacokinetics. Compared with L-GNCs, D-GNCs do not exhibit cellular cytotoxicity, hemolysis, or acute damage to organs. Cationic D-GNCs show less cell internalization than L-GNCs, and do not induce cellular apoptosis. In vivo, the chirality of surface ligands distinctly affects the pharmacokinetics and tumor targeting abilities of D-/L-GNCs. D-GNCs show higher extended circulation time in blood plasma compared to similarly-sized and poly (ethylene glycol)-modified gold nanoparticles. This work demonstrates that the choice of chirality of surface ligands can determine toxicities and pharmacokinetics of cationic nanomaterials.

Anti-Coronaviral Nanocluster Restrain Infections of SARS-CoV-2 and Associated Mutants through Virucidal Inhibition and 3CL Protease Inactivation.

Antivirals that can combat coronaviruses, including SARS-CoV-2 and associated mutants, are urgently needed but lacking. Simultaneously targeting the viral physical structure and replication cycle can endow antivirals with sustainable and broad-spectrum anti-coronavirus efficacy, which is difficult to achieve using a single small-molecule antiviral. Thus, a library of nanomaterials on GX_P2V, a SARS-CoV-2-like coronavirus of pangolin origin, is screened and a surface-functionalized gold nanocluster (TMA-GNC) is identified as the top hit. TMA-GNC inhibits transcription- and replication-competent SARS-CoV-2 virus-like particles and all tested pseudoviruses of SARS-CoV-2 variants. TMA-GNC prevents viral dissemination through destroying membrane integrity physically to enable a virucidal effect, interfering with viral replication by inactivating 3CL protease and priming the innate immune system against coronavirus infection. TMA-GNC exhibits biocompatibility and significantly reduces viral titers, inflammation, and pathological injury in lungs and tracheas of GX_P2V-infected hamsters. TMA-GNC may have a role in controlling the COVID-19 pandemic and inhibiting future emerging coronaviruses or variants.

Aminophenol-modified gold nanoparticles kill bacteria with minimal ototoxicity.

We report aminophenol (A)-modified gold nanoparticles (AGNPs), which have potent antibacterial effects against multidrug-resistant bacteria with a broad antibacterial spectrum. Moreover, a series of in vitro and in vivo models indicate that AGNPs are much less ototoxic than aminoglycosides. AGNPs thus have the potential to replace aminoglycosides as novel antibacterial agents for clinical applications.

Facile and Controllable Synthesis of the Renal-Clearable "Luminous Pearls" for in Vivo Afterglow/Magnetic Resonance Imaging.

To date, the strategic exploration of a synthetic approach to afford persistent luminescent nanoparticles (PLNPs) integrated with precisely controlled size/monodispersity and renal-clearable capability remains extremely challenging. Herein, we report a facile synthetic process with an elucidated mechanism to fine-tune the size for acquiring renal-clearable PLNPs, using mesoporous silica nanoparticles (MSNs) as a template. This strategy relies on the controlled crystallization of the precursor ions in the pore channels of MSNs at a high temperature, leading to the formation of monodispersed PLNPs with an average diameter as small as 2.5 nm after complete removal of MSN templates. The as-prepared ultrasmall PLNPs coated with polyethylene glycol exhibit uniform size, excellent water-dispersibility, good persistent luminescence, and high T1 relaxivity (17.6 mM-1·S-1), ensuring their suitability for afterglow/magnetic resonance dual-modality imaging and subsequent in vivo renal clearance. Thus, our study provides a strategy to inspire the controlled synthesis of diverse PLNPs by using MSN templates, simultaneously addressing the critical issues of precise adjustment of size and body clearance for versatile biomedical applications.

Breathable and Stretchable Dressings for Accelerating Healing of Infected Wounds.

Multidrug-resistant (MDR) bacteria-infected wounds are challenging issues that threaten human health. Herein, L-thioproline (T) and Boc-capped L-thioproline (BT)-decorated gold nanoparticles (TBT-GNPs) with potent antibacterial activity against MDR bacteria are reported. The TBT-GNPs are composited with bacterial cellulose to form wound dressings which show excellent antimicrobial performance both in vitro and in vivo. Moreover, this dressing is both breathable and stretchable which is favorable for gas exchange to accelerate the wound healing. This work is insightful for developing multifunctional dressings to satisfy the clinical requirements.

Multifunctional Gold Nanoclusters for Effective Targeting, Near-Infrared Fluorescence Imaging, Diagnosis, and Treatment of Cancer Lymphatic Metastasis.

Developing effective lymph-node (LN) targeting and imaging probes is crucial for the early detection and diagnosis of tumor metastasis to improve patient survival. Most current clinical LN imaging probes are based on small organic dyes (e.g., indocyanine green) or radioactive 99mTc-complexes, which often suffer from limitations, such as rapid photobleaching, poor signal contrast, and potential biosafety issues. Moreover, these probes cannot easily incorporate therapeutic functions to realize beneficial theranostics without affecting their LN-targeting ability. Herein, we have developed dual-ligand-/multiligand-capped gold nanoclusters (GNCs) for specific targeting, near-infrared (NIR) fluorescence imaging, diagnosis, and treatment of LN cancer metastasis in in vivo mouse models. By optimizing the surface ligand coating, we have prepared Au25(SR1)n(SR2)18-n (where SR1 and SR2 are different functional thiol ligands)-type GNCs, which display highly effective LN targeting, excellent stability and biocompatibility, and optimal body-retention time. Moreover, they can provide continuous NIR fluorescence imaging of LNs for >3 h from a single dose, making them well-suited for fluorescence-guided surgery. Importantly, we have further incorporated methotrexate, a chemotherapeutic drug, into the GNCs without affecting their LN-targeting ability. Consequently, they can significantly improve the efficiency of methotrexate delivery to target LNs, achieving excellent therapeutic efficacy with up to 4-fold lower hepatotoxicity. Thus, the GNCs are highly effective and safe theranostic nanomedicines against cancer lymphatic metastasis.

Ultrasensitive point-of-care biochemical sensor based on metal-AIEgen frameworks.

Point-of-care (POC) biochemical sensors have found broad applications in areas ranging from clinical diagnosis to environmental monitoring. However, POC sensors often suffer from poor sensitivity. Here, we synthesized a metal-organic framework, where the ligand is the aggregation-induced emission luminogen (AIEgen), which we call metal-AIEgen frameworks (MAFs), for use in the ultrasensitive POC biochemical sensors. MAFs process a unique luminescent mechanism of structural rigidity-enhanced emission to achieve a high quantum yield (~99.9%). We optimized the MAFs to show 102- to 103-fold enhanced sensitivity for a hydrogel-based POC digital sensor and lateral flow immunoassays (LFIA). MAFs have a high affinity to directly absorb proteins, which can label antibodies for immunoassays. MAFs-based LFIA with enhanced sensitivity shows robust serum detection for POC clinical diagnosis.

Superassembly of Surface-Enriched Ru Nanoclusters from Trapping-Bonding Strategy for Efficient Hydrogen Evolution.

Hydrogen evolution reaction (HER) through water splitting is a potential technology to realize the sustainable production of hydrogen, yet the tardy water dissociation and costly Pt-based catalysts inhibit its development. Here, a trapping-bonding strategy is proposed to realize the superassembly of surface-enriched Ru nanoclusters on a phytic acid modified nitrogen-doped carbon framework (denoted as NCPO-Ru NCs). The modified framework has a high affinity to metal cations and can trap plenty of Ru ions. The trapped Ru ions are mainly distributed on the surface of the framework and can form Ru nanoclusters at 50 °C with the synergistic effect of vacancies and phosphate groups. By adjusting the content of phytic acid, surface-enriched Ru nanoclusters with adjustable distribution and densities can be obtained. Benefiting from the adequate exposure of the active sites and dense distribution of ultrasmall Ru nanoclusters, the obtained NCPO-Ru NCs catalyst can effectively drive HER in alkaline electrolytes and show an activity (at overpotential of 50 mV) about 14.3 and 9.6 times higher than that of commercial Ru/C and Pt/C catalysts, respectively. Furthermore, the great performance in solar to hydrogen generation through water splitting provides more flexibility for wide applications of NCPO-Ru NCs.

A High Conductivity 1D π-d Conjugated Metal-Organic Framework with Efficient Polysulfide Trapping-Diffusion-Catalysis in Lithium-Sulfur Batteries.

The shuttling behavior and sluggish conversion kinetics of the intermediate lithium polysulfides (LiPS) represent the main obstructions to the practical application of lithium-sulfur batteries (LSBs). Herein, a 1D π-d conjugated metal-organic framework (MOF), Ni-MOF-1D, is presented as an efficient sulfur host to overcome these limitations. Experimental results and density functional theory calculations demonstrate that Ni-MOF-1D is characterized by a remarkable binding strength for trapping soluble LiPS species. Ni-MOF-1D also acts as an effective catalyst for S reduction during the discharge process and Li2 S oxidation during the charging process. In addition, the delocalization of electrons in the π-d system of Ni-MOF-1D provides a superior electrical conductivity to improve electron transfer. Thus, cathodes based on Ni-MOF-1D enable LSBs with excellent performance, for example, impressive cycling stability with over 82% capacity retention over 1000 cycles at 3 C, superior rate performance of 575 mAh g-1 at 8 C, and a high areal capacity of 6.63 mAh cm-2 under raised sulfur loading of 6.7 mg cm-2 . The strategies and advantages here demonstrated can be extended to a broader range of π-d conjugated MOFs materials, which the authors believe have a high potential as sulfur hosts in LSBs.

Nanoscale Metal-Organic Frameworks That are Both Fluorescent and Hollow for Self-Indicating Drug Delivery.

Nanoscale metal-organic frameworks (MOFs) that are both fluorescent and hollow are attracting increasing interest in recent years, but ideal candidates prepared by reliable methods for biomedical applications are still very limited. Herein, we for the first time prepared tetrakis[4-(4-carboxyphenyl)phenyl]ethene (TCBPE)-based MOF nanotubes with hollow nanostructures, which could emit strong fluorescence. It was further discovered that the formation of this hollow hexagonal nanotube underwent a self-templated growth and a subsequent concaving process, which revealed that the synthesis of this MOF was kinetic rather than thermodynamic. This new MOF showed high biocompatibility, optical stability, sensitivity to pH response, and capability for exotic loading. This new MOF was further employed for efficient anti-cancer drug delivery in a self-indicating manner based on these attractive features. Therefore, this work could bring in valuable insights into the exploration of multifunctional MOFs in the field of biomedical applications by providing a new exemplar with high practical utility.

Evaluation of the in vivo behavior of antibacterial gold nanoparticles for potential biomedical applications.

The pharmacokinetics is a critical factor determining the clinical applicability of nanomaterials. Systematic study of the pharmacokinetics of functional nanomaterials is thus significant for promoting their applications. Herein, we take aminophenylboronic acid and mercaptophenylboronic acid-co-modified gold nanoparticles (A/M-Au NPs) with potent and tunable antibacterial activity as an example to study their behaviors in vitro and in vivo. The maximum concentration (Cmax, 2 mg L-1), the time to reach the maximum concentration (Tmax, 6 h), and the half-life (T1/2, 12 h) in the plasma of mice reflect appropriate pharmacokinetics of the gold nanoparticles as an ideal nano-antibiotic. Strikingly, the A/M-Au NPs show an extremely high median lethal dose (920 mg kg-1), which is about 100 times their effective dose (7.2 mg kg-1), suggesting their outstanding biosafety. The adequate pharmacokinetic profile and the high biosafety of the gold nanoparticles pave the way for their potential biomedical applications.

Controlling the pyridinium-zwitterionic ligand ratio on atomically precise gold nanoclusters allowing for eradicating Gram-positive drug-resistant bacteria and retaining biocompatibility.

Infections caused by multidrug-resistant (MDR) bacteria are an increasing global healthcare concern. In this study, we developed a dual-ligand-functionalised Au25(SR1) x (SR2)18-x -type gold nanocluster and determined its antibacterial activity against MDR bacterial strains. The pyridinium ligand (SR1) provided bactericidal potency and the zwitterionic ligand (SR2) enhanced the stability and biocompatibility. By optimising the ligand ratio, our gold nanocluster could effectively kill MDR Gram-positive bacteria via multiple antibacterial actions, including inducing bacterial aggregation, disrupting bacterial membrane integrity and potential, and generating reactive oxygen species. Moreover, combining the optimised gold nanocluster with common antibiotics could significantly enhance the antibacterial activity against MDR bacteria both in in vitro and animal models of skin infections. Furthermore, the fluorescence of the gold nanocluster at the second near-infrared (NIR-II) biological window allowed for the monitoring of its biodistribution and body clearance, which confirmed that the gold nanoclusters had good renal clearance and biocompatibility. This study provides a new strategy to combat the MDR challenge using multifunctional gold nanomaterials.

Ligand-regulated self-assembly of luminescent Au nanoparticles towards diverse controllable superstructures.

Only using one type of amphiphilic block copolymers as a template, we present a facile and robust approach to in situ fabricate a series of brightly emitting Au nano-assemblies with high controllability and tunability. Simply by altering thiol ligands, the Au nano-assemblies display diverse superstructures including fibers, vesicles, and honeycombs.