Emerging trends in chiral inorganic nanomaterials for enantioselective catalysis.

Asymmetric transformations and synthesis have garnered considerable interest in recent decades due to the extensive need for chiral organic compounds in biomedical, agrochemical, chemical, and food industries. The field of chiral inorganic catalysts, garnering considerable interest for its contributions to asymmetric organic transformations, has witnessed remarkable advancements and emerged as a highly innovative research area. Here, we review the latest developments in this dynamic and emerging field to comprehensively understand the advances in chiral inorganic nanocatalysts and stimulate further progress in asymmetric catalysis.

Modulation by Co (II) Ion of Optical Activities of L/D-glutathione (GSH)-modified Chiral Copper Nanoclusters for Sensitive Adenosine Triphosphate Detection.

Chiral nanoscale enantiomers exhibit different biological effects in living systems. However, their chirality effect on the detection sensitivity for chiral biological targets still needs to be explored. Here, we discovered that Co2+ can modulate the luminescence performance of L/D-glutathione (GSH)-modified copper nanoclusters (L/D-Cu NCs) and induce strong chiroptical activities as the asymmetric factor was enhanced 223-fold with their distribution regulating from the ultraviolet to visible region. One Co2+ coordinated with two GSH molecules that modified on the surface of Cu NCs in the way of CoN2O2. On this basis, dual-modal chiral and luminescent signals of Co2+ coordinated L/D-Cu NCs (L/D-Co-Cu NCs) were used to detect the chiral adenosine triphosphate (ATP) based on the competitive interaction between surficial GSH and ATP molecules with Co2+. The limits of detection of ATP obtained with fluorescence and circular dichroism intensity were 9.15 µM and 15.75 nM for L-Co-Cu NCs, and 5.35 µM and 4.69 nM for D-Co-Cu NCs. This demonstrated that selecting suitable chiral configurations of nanoprobes effectively enhances detection sensitivity. This study presents not only a novel method to modulate and enhance the chiroptical activity of nanomaterials but also a unique perspective of chirality effects on the detection performances for bio-targets.

Controllable Assembly of Cu2+ and Chlorin E6 for H2 S-Activatable Recognition of Bacterial Infection and Enhanced Antibacterial Therapy.

Antibacterial photodynamic therapy (APDT) has emerged as one of the intriguing strategies to combat bacterial resistance. However, the antibacterial efficacy of APDT is found to be severely impacted by the hydrogen sulfide (H2 S)-overproduced bacterial infection microenvironment. Herein, a multifunctional APDT platform is developed by assembling Cu2+ and chlorin e6 (Ce6), which exhibits unique H2 S-activatable fluorescence (FL) and antibacterial features. Noteworthily, the assembly conditions are crucial for achievement of Cu-Ce6 nanoassemblies (NAs) with the on-demand responsive properties. The quenched FL and photosensitization of Cu-Ce6 NAs can be selectively activated by the overexpressed H2 S in infected area, enabling specific recognition of bacterial infection and localized antibacterial therapy with minimized side effects. Significantly, amplified oxidative stress is achieved owning to the effective consumption of H2 S by Cu2+ in the NAs, leading to an enhanced APDT. The antibacterial mechanisms including broad-spectrum APDT activity of released Ce6, inherent sterilization effects of produced copper polysulfides and the accompanying disturbance of bacterial sulphide metabolism are further identified. This study may pave a new avenue for the rational design of intelligent APDT platform using minimalist biological building units and thus facilitating the clinical translation of nano-antibacterial agents.

Chiral Cux Coy S-Cuz S Nanoflowers with Bioinspired Enantioselective Catalytic Performances.

Nanomaterials with biomimetic catalytic abilities have attracted significant attention. However, the stereoselectivity of natural enzymes determined by their unique configurations is difficult to imitate. In this work, a kind of chiral Cux Coy S-Cuz S nanoflowers (L/D-Pen-NFs) is developed, using porous Cux Coy S nanoparticles (NPs) as stamens, Cuz S sheets as petals, and chiral penicillamine as surface stabilizers. Compared to the natural laccase enzyme, L/D-Pen-NFs exhibit significant advantages in catalytic efficiency, stability against harsh environments, recyclability, and convenience in construction. Most importantly, they display high enantioselectivity toward chiral neurotransmitters, which is proved by L- and D-Pen-NFs' different catalytic efficiencies toward chiral enantiomers. L-Pen-NFs are more efficient in catalyzing the oxidation of L-epinephrine and L-dopamine compared with D-Pen-NFs. However, their catalytic efficiency in oxidizing L-norepinephrine and L-DOPA is lower than that of D-Pen-NFs. The reason for the difference in catalytic efficiency is the distinct binding affinities between Cux Coy S-Cuz S nano-enantiomers and chiral molecules. This work can spur the development of chiral nanostructures with biomimetic functions.

Facilitating Near-Infrared Persistent Luminescence in Cr3+ -Doped Gadolinium Gallium Garnets.

Near-infrared persistent luminescence (NIR PersL) materials provide great potential in the fields of night vision, biological imaging, and information encryption. However, among various crystal structures, Cr3+ -doped gallium garnets show inferior PersL property, which turns out to be the bottleneck of their versatile applications. The rational design and facile preparation of high-performance NIR PersL materials are crucial for the emerging applications. In this work, a series of Gd3 Mgx Gex Ga5-2x O12 :Cr3+ (x = 0, 0.25, 0.5, 0.75, 1) is investigated by microwave-assisted solid-state (MASS) approach. Furthermore, by employing chemical composition co-substitution, PersL performance is further improved and the optimum working temperature is adjusted to the lower temperature at 10 °C. Trap level distribution of Gd3 Mg0.5 Ge0.5 Ga4 O12 :Cr3+ phosphor is revealed based on the temperature and fading-time dependent PersL and thermoluminescence property. Further study demonstrates the reduction of the bandgap and the trap distribution forwards at shallow-lying trap energy levels. The synergistic effect, from both energy-band manipulation and trap-level optimization, facilitates NIR PersL in Cr3+ -doped gadolinium gallium garnets. These findings confirm the applicability of MASS-based bandgap and defect level engineering for improving the PersL properties in non/inferior-PersL materials. This burgeoning MASS method may facilitate a wide range of PersL materials for various emerging applications.

Activation-Induced Senescent Cell Death based on Chiral CoHAu Nanoassemblies with Enantioselective Cascade-Catalytic Ability.

Chirality is common in nature, which determines the high enantioselectivity of living systems. Selecting suitable chiral configurations is of great meaning for nanostructures to function better in biological systems. In this study, chiral Co3O4-H2TPPS-Au (CoHAu) nanoassemblies are constructed to accelerate the production ∙OH by consuming D-glucose (D-Glu, widely spread in nature) based on their outstanding enantioselective cascade-catalytic abilities. In particular, D-CoHAu nanoassemblies are more effective in the catalytic conversion of D-Glu than L-CoHAu nanoassemblies. This phenomenon is due to the stronger binding affinity of D-CoHAu nanoassemblies indicated by the lower Km value. Moreover, D-CoHAu nanoassemblies display excellent consumption-ability of D-Glu and production of ∙OH in living cells, which can eliminate senescent cells effectively based on their intracellular enantioselective cascade-catalysis. This research establishes the foundation for bio-mimicking nanostructures with unique functionalities to regulate abnormal biological activities better.

Visualizing temperature inhomogeneity using thermo-responsive smart materials.

Despite the substantial progress made, the responsiveness of thermo-responsive materials upon various thermal fields is still restricted to monochromatic visualization with single-wavelength light emission. This stems from a poor understanding of the photophysical processes within the materials and the unvarying optical performance of luminescent centers' response to various ambient temperatures. Conventional techniques to assess the inhomogeneities of thermal fields can be time-consuming, require specialized equipment and suffer from inaccuracy due to the inevitable interference from background signals, especially at high temperature. To this end, we overcome these limitations for the first time, to flexibly visualize temperature inhomogeneities by developing a thermochromic smart material, SrGa12-xAlxO19:Dy3+. Two distinct modes of thermochromic properties (steady-state temperature-dependent luminescence and thermally stimulated luminescence) are investigated. It is revealed that the abundant colors (from yellow, green to red) and amazing color-changing features are due to the superior optical integration of the host (SrGa12-xAlxO19) and dopant (Dy3+) emissions under specific thermal stimulations. We suggest that this thermo-responsive smart material can be used to realize highly efficient and simple visualization of invisible thermal distribution in industry and beyond.

Construction of Pt/Pt-Au doped chiral nanostructures using arginine and porphyrin assemblies as templates for enantioselective photocatalysis.

Chiral nanomaterials with different functions have been widely developed, but the deep understanding of the structural effects of nanocatalysts on enantioselective photocatalytic efficiency is still highly demanded. Herein, Pt and Pt-Au-bimetal-doped chiral nanostructures with various morphologies and compositions are facilely constructed using L-/D-arginine (L-/D-Arg) and mono-sulfonate tetraphenyl porphyrin (H2TPPS) assemblies as chiral templates. Interestingly, these Pt and Pt-Au-doped chiral nanostructures, including nanorods (NR) and nanospheres (NS), can be well regulated by controlling pH, ionic strength, and reaction time of the assembling system of Arg and H2TPPS. More impressively, specific Au growth direction along the Pt-doped chiral NR (L-/D-Pt-NR) is observed (from tip to middle) during the preparation of Pt-Au-bimetal-doped chiral NR (L-/D-Pt-Au-NR) and their compositions can be finely controlled by simply adjusting the concentrations of HAuCl4. As expected, the chiral nanostructures exhibit superior enantioselective photocatalytic ability toward chiral organics under visible light: the oxidation rate of L-dihydroxy-phenylalanine (L-DOPA) catalyzed by L-Pt-NR (or D-DOPA catalyzed by D-Pt-NR) is about 60% higher than that of L-DOPA catalyzed by D-Pt-NR (or L-DOPA catalyzed by D-Pt-NR). This study provides a facile strategy to construct chiral nanostructures for the photocatalytic conversion of chiral organics.

Specific Chemiluminescence Imaging and Enhanced Photodynamic Therapy of Bacterial Infections by Hemin-Modified Carbon Dots.

Antibacterial photodynamic therapy (aPDT) is a promising antibiotics-alternative strategy for bacterial infectious diseases, which features broad-spectrum antibacterial activity with a low risk of inducing bacterial resistance. However, clinical applications of aPDT are still hindered by the hydrophobicity-caused inadequate photodynamic activity of conventional photosensitizers and the hypoxic microenvironment of bacterial infections. To address these problems, herein, a promising strategy is developed to achieve specific chemiluminescence (CL) imaging and enhanced PDT of bacterial infections using hemin-modified carbon dots (H-CDs). The H-CDs can be facilely prepared and exhibit favorable water solubility, augmented photodynamic activity, and unique peroxidase-mimicking capacity. Compared with the free CDs, the photodynamic efficacy of H-CDs is significantly augmented due to the increased electron-hole separation efficiency. Moreover, the peroxidase catalytic performance of H-CDs enables not only infection identification via bacterial infection microenvironment-responsive CL imaging but also oxygen self-supplied aPDT with hypoxia-relief-enhanced bacteria inactivation effects. Finally, the enhanced aPDT efficiencies of H-CDs are validated in both in vivo abscess and infected wound models. This work may provide an effective antibacterial platform for the selective imaging-guided treatment of bacterial infections.

A near-infrared fluorescent nanoprobe for senescence-associated ß-galactosidase sensing in living cells.

A near-infrared fluorescent nanoprobe based on semiconducting polymer nanoparticles (SPNs) for the detection of senescence-associated ß-gal (SA-ß-gal) is developed. Benefiting from the intrinsic lysosome-locating feature, this probe can be successfully used for the visualization of SA-ß-gal in living cells.

Chiral inorganic nanomaterials for biological applications.

Chiral nanomaterials in biology play indispensable roles in maintaining numerous physiological processes, such as signaling, site-specific catalysis, transport, protection, and synthesis. Like natural chiral nanomaterials, chiral inorganic nanomaterials can also be established with similar size, charge, surface properties, and morphology. However, chiral inorganic nanomaterials usually exhibit extraordinary properties that are different from those of organic materials, such as high g-factor values, broad distribution range, and symmetrical mirror configurations. Because of these unique characteristics, there is great potential for application in the fields of biosensing, drug delivery, early diagnosis, bio-imaging, and disease therapy. Related research is summarized and discussed in this review to showcase the bio-functions and bio-applications of chiral inorganic nanomaterials, including the construction methods, classification and properties, and biological applications of chiral inorganic nanomaterials. Moreover, the deficiencies in existing studies are noted, and future development is prospected. This review will provide helpful guidance for constructing chiral inorganic nanomaterials with specific bio-functions for problem solving in living systems.

Enantiomeric NIR-II Emitting Rare-Earth-Doped Ag2 Se Nanoparticles with Differentiated In Vivo Imaging Efficiencies.

Here, chiral second near-infrared (NIR-II) emitting rare-earth doped silver selenide nanoparticles (R- or S-Ag2 Se:Nd/Yd/Er NPs) were fabricated, exhibiting circular dichroism peak at 850 nm and fluorescence peak at 1550 nm, with 145.7-fold enhanced intensity compared to the reported Ag2 Se NPs. Compared with S-Ag2 Se:Nd/Yd/Er NPs, imaging efficiency of R-Ag2 Se:Nd/Yd/Er NPs in living cells was significantly improved due to a higher cellular uptake rate and 927.7-fold higher affinity. Furthermore, R-Ag2 Se:Nd/Yd/Er NPs reached at the tumor 2-fold faster than S type of NPs in vivo. We discover that chirality leads to differences in the affinity between chiral Ag2 Se:Nd/Yd/Er NPs and cluster of differentiation 44 (CD44) onto the surface of murine mammary carcinoma cell to cause different in vivo imaging efficiency. These results reveal that chiral Ag2 Se:Nd/Yd/Er NPs have high photoluminescence intensity and high in vivo imaging efficiency reflecting wide applications in biomedical diagnosis.

Biomolecule-based stimuli-responsive nanohybrids for tumor-specific and cascade-enhanced synergistic therapy.

Poor tumor specificity is one of the key obstacles for clinical applications of nanotheranostic agents, consequently leading to serious side effects and unsatisfactory therapeutic efficacy. Herein, biomolecule-based nanohybrids (named as Hb-PDA-GOx) with multiple stimuli-responsiveness were designed and fabricated to enhance tumor-specific therapy. The nanohybrids embodied two proteins, i.e., hemoglobin (Hb) and glucose oxidase (GOx), which exhibited cascade catalytic activity selectively within the tumor microenvironment (TME). Specifically, GOx catalyzes the overexpressed glucose into gluconic acid and hydrogen peroxide (H2O2), which not only initiated starvation therapy (ST) through cutting off the nutrition supply for carcinoma cells, but also provided H2O2 for sequential Fenton reaction induced by Hb that generating biotoxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT). Moreover, localized heat generation from polydopamine (PDA) in the nanohybrids can implement photothermal therapy (PTT) and reinforce the CDT efficacy. Excitingly, effective eradication of solid tumors and significant suppression of metastatic tumors growth were achieved by utilizing Hb-PDA-GOx as a versatile theranostic agent. All these results had been verified by in vitro and/or in vivo experiments. In light of the superior anticancer effects and insignificant systemic toxicity, the as-fabricated biomolecule-based nanohybrids could be employed as a promising agent for tumor-specific therapy. More importantly, the high biocompatibility and biodegradability of the selected biomolecules would facilitate subsequent clinical translation. STATEMENT OF SIGNIFICANCE: (1) A facile one-pot synthesis strategy was proposed to fabricate biomolecule-based tumor theranostic agent with high biocompatibility and biodegradability, which would facilitate subsequent clinical translation; (2) The as-developed theranostic agent was endowed with multiple stimuli-responsiveness for achieving tumor-specific and cascade-enhanced synergistic therapy; (3) The in vivo experiments demonstrated that the as-developed theranostic agent can not only effectively eradicate solid tumors, but also significantly suppress metastatic tumors growth.

Proactive functional classification of all possible missense single-nucleotide variants in KCNQ4.

Clinical exome sequencing has yielded extensive disease-related missense single-nucleotide variants (SNVs) of uncertain significance, leading to diagnostic uncertainty. KCNQ4 is one of the most commonly responsible genes for autosomal dominant nonsyndromic hearing loss. According to the gnomAD cohort, approximately one in 100 people harbors missense variants in KCNQ4 (missense variants with minor allele frequency > 0.1% were excluded), but most are of unknown consequence. To prospectively characterize the function of all 4085 possible missense SNVs of human KCNQ4, we recorded the whole-cell currents using the patch-clamp technique and categorized 1068 missense SNVs as loss of function, as well as 728 loss-of-function SNVs located in the transmembrane domains. Further, to mimic the heterozygous condition in Deafness nonsyndromic autosomal dominant 2 (DFNA2) patients caused by KCNQ4 variants, we coexpressed loss-of-function variants with wild-type KCNQ4 and found 516 variants showed impaired or only partially rescued heterogeneous channel function. Overall, our functional classification is highly concordant with the auditory phenotypes in Kcnq4 mutant mice and the assessments of pathogenicity in clinical variant interpretations. Taken together, our results provide strong functional evidence to support the pathogenicity classification of newly discovered KCNQ4 missense variants in clinical genetic testing.

Endowing matrix-free carbon dots with color-tunable ultralong phosphorescence by self-doping.

Color-tunable ultralong phosphorescence is urgently desired in optoelectronic applications. Herein, we report a new type of full-color-tunable ultralong phosphorescence carbon dots (CDs) without matrix-assistance by a self-doping method under ambient conditions. The phosphorescence color can be rationally tuned from blue to red by changing the excitation wavelength from 310 to 440 nm. The CDs exhibit an ultralong lifetime of up to 1052.23 ms at 484 nm. From the experimental data, we speculate that the excitation-dependent multi-color phosphorescence is attributed to the presence of multiple emitting centers related to carbonyl units. Given the unique color-tunability of CDs, we demonstrate their potential applications in information encryption, light detection ranging from UV to visible light and LED devices. This finding not only takes a step towards the fundamental design of full-color emissive materials, but also provides a broader scope for the applications of phosphorescent materials.

Enabling robust and hour-level organic long persistent luminescence from carbon dots by covalent fixation.

The first carbon dot (CD)-based organic long persistent luminescence (OLPL) system exhibiting more than 1 h of duration was developed. In contrast to the established OLPL systems, herein, the reported CDs-based system (named m-CDs@CA) can be facilely and effectively fabricated using a household microwave oven, and more impressively, its LPL can be observed under ambient conditions and even in aqueous media. XRD and TEM characterizations, afterglow decay, time-resolved spectroscopy, and ESR analysis were performed, showing the successful composition of CDs and CA, the formation of exciplexes and long-lived charged-separated states. Further studies suggest that the production of covalent bonds between CA and CDs plays pivotal roles in activating LPL and preventing its quenching from oxygen and water. To the best of our knowledge, this is a very rare example of an OLPL system that exhibits hour-level afterglow under ambient conditions. Finally, applications of m-CDs@CA in glow-in-the-dark paints for emergency signs and multicolored luminous pearls were preliminarily demonstrated. This work may provide new insights for the development of rare-earth-free and robust OLPL materials.

Programmed Stimuli-Responsive Carbon Dot-Nanogel Hybrids for Imaging-Guided Enhanced Tumor Phototherapy.

For harmonizing the contradiction of nanotheranostic agents between enhanced tumor accumulation and penetration, efficient cell internalization and fast elimination are key tactics for promoting their clinical applications. Herein, programmed stimuli-responsive poly(N-isopropylacrylamide)-carbon dot (PNIPAM-CD) hybrid nanogels are designed to address the abovementioned conflicts. The enlarged particle size of PNIPAM-CDs enables one to effectively improve their accumulation at tumor sites. Once the hybrid nanogels are docked in tumors and exposed to deep-red-light (660 nm) irradiation, heat and reactive oxygen species (ROS) are generated from the CDs, consequently activating photothermal therapy (PTT) and photodynamic therapy (PDT) effects and meanwhile inducing partial degradation of PNIPAM-CDs for deep tissue penetration. Further, enhanced cellular internalization of the functional components can be achieved owing to the pH-responsive charge reversal and temperature-dependent hydrophilic/hydrophobic conversion characteristics of PNIPAM-CDs. Finally, the overexpressed glutathione (GSH) in tumor cells would trigger further cleavage of the partially degraded hybrid nanogels, which is beneficial for their rapid clearance from the body. This work not only proposed a novel strategy to fabricate nanotheranostic agents using just a single functional component (i.e., the versatile CDs) to simplify the preparation process but also achieved effective delivery of agents into tumor cells by overcoming the multiple biological barriers to enhance therapeutic efficacy and decrease side effects.

Green and Near-Infrared Dual-Mode Afterglow of Carbon Dots and Their Applications for Confidential Information Readout.

Near-infrared (NIR), particularly NIR-containing dual-/multi-mode afterglow, is very attractive in many fields of application, but it is still a great challenge to achieve such property of materials. Herein, we report a facile method to prepare green and NIR dual-mode afterglow of carbon dots (CDs) through in situ embedding o-CDs (being prepared from o-phenylenediamine) into cyanuric acid (CA) matrix (named o-CDs@CA). Further studies reveal that the green and NIR afterglows of o-CDs@CA originate from thermal activated delayed fluorescence (TADF) and room temperature phosphorescence (RTP) of o-CDs, respectively. In addition, the formation of covalent bonds between o-CDs and CA, and the presence of multiple fixation and rigid effects to the triplet states of o-CDs are confirmed to be critical for activating the observed dual-mode afterglow. Due to the shorter lifetime and insensitiveness to human vision of the NIR RTP of o-CDs@CA, it is completely covered by the green TADF during directly observing. The NIR RTP signal, however, can be readily captured if an optical filter (cut-off wavelength of 600 nm) being used. By utilizing these unique features, the applications of o-CDs@CA in anti-counterfeiting and information encryption have been demonstrated with great confidentiality. Finally, the as-developed method was confirmed to be applicable to many other kinds of CDs for achieving or enhancing their afterglow performances.

Modulating Triplet Excited-State Energy in Phosphorescent Carbon Dots for Information Encryption and Anti-Counterfeiting.

Room-temperature phosphorescent carbon dots (RTP-CDs) may be used in anti-counterfeiting, information encryption, and optoelectronic devices, but modulating their triplet-state energy is still challenging. Here, a type of RTP-CDs was developed via hydrothermal polymerization-carbonization of azamacrocycle and poly(acrylic acid). The introduction of nitrogen heterocycle promotes the intersystem crossing from the singlet state to the triplet state, and the functional groups of CDs can form interdot hydrogen bonds to protect the triplet state. In addition, the uncarbonized heterocycle groups in the CDs provide coordination sites for metal ions. In this case, the excited triplet-state energy of CDs is quenched by paramagnetic ions (Co2+ and Cu2+) or transfers to luminescent ions (Tb3+ and Eu3+). Furthermore, the modulation of the triplet state by metal ion binding was demonstrated in information encryption and anti-counterfeiting applications.

Supra-Carbon Dots Formed by Fe3+-Driven Assembly for Enhanced Tumor-Specific Photo-Mediated and Chemodynamic Synergistic Therapy.

We herein report a facile method to fabricate a multifunctional cancer theranostic nanoplatform via Fe3+-driven assembly of photosensitizer (chlorine e6, Ce6)-decorated red emissive carbon dots (Ce6-RCDs). The as-prepared Supra-CDs (i.e., CD clusters; also termed as Fe-Ce6-RCDs) are found to not only retain the intrinsic photosensitization, fluorescence (FL), and photothermal properties of the Ce6-RCDs component but also be endowed with the chemodynamic therapy (CDT) function by the introduced Fe3+via the Fenton reaction that can specifically occur in tumor sites. The suitable size (∼36 nm) of the Supra-CDs enables enhanced tumor accumulation, thus achieving significantly improved FL imaging-guided anticancer performance by combining photodynamic, photothermal, and chemodynamic therapeutic modalities. More interestingly, the multi-subcellular structure (including nucleolus and cytoplasm)-targeting capacity of the Supra-CDs further enhances their therapeutic outcomes. This work not only develops a Fe3+-mediated self-assembly approach to construct a multifunctional cancer theranostic nanoplatform but also emphasizes the ion-interference role of the Fe3+-mediated CDT in anticancer nanomedicines.