Enantiomer-dependent immunological response to chiral nanoparticles.

Chirality is a unifying structural metric of biological and abiological forms of matter. Over the past decade, considerable clarity has been achieved in understanding the chemistry and physics of chiral inorganic nanoparticles1-4; however, little is known about their effects on complex biochemical networks5,6. Intermolecular interactions of biological molecules and inorganic nanoparticles show some commonalities7-9, but these structures differ in scale, in geometry and in the dynamics of chiral shapes, which can both impede and strengthen their mirror-asymmetric complexes. Here we show that achiral and left- and right-handed gold biomimetic nanoparticles show different in vitro and in vivo immune responses. We use irradiation with circularly polarized light (CPL) to synthesize nanoparticles with controllable nanometre-scale chirality and optical anisotropy factors (g-factors) of up to 0.4. We find that binding of nanoparticles to two proteins from the family of adhesion G-protein-coupled receptors (AGPCRs)-namely cluster-of-differentiation 97 (CD97) and epidermal-growth-factor-like-module receptor 1 (EMR1)-results in the opening of mechanosensitive potassium-efflux channels, the production of immune signalling complexes known as inflammasomes, and the maturation of mouse bone-marrow-derived dendritic cells. Both in vivo and in vitro immune responses depend monotonically on the g-factors of the nanoparticles, indicating that nanoscale chirality can be used to regulate the maturation of immune cells. Finally, left-handed nanoparticles show substantially higher (1,258-fold) efficiency compared with their right-handed counterparts as adjuvants for vaccination against the H9N2 influenza virus, opening a path to the use of nanoscale chirality in immunology.

Tapered chiral nanoparticles as broad-spectrum thermally stable antivirals for SARS-CoV-2 variants.

The incessant mutations of viruses, variable immune responses, and likely emergence of new viral threats necessitate multiple approaches to novel antiviral therapeutics. Furthermore, the new antiviral agents should have broad-spectrum activity and be environmentally stable. Here, we show that biocompatible tapered CuS nanoparticles (NPs) efficiently agglutinate coronaviruses with binding affinity dependent on the chirality of surface ligands and particle shape. L-penicillamine-stabilized NPs with left-handed curved apexes display half-maximal inhibitory concentrations (IC50) as low as 0.66 pM (1.4 ng/mL) and 0.57 pM (1.2 ng/mL) for pseudo-type SARS-CoV-2 viruses and wild-type Wuhan-1 SARS-CoV-2 viruses, respectively, which are about 1,100 times lower than those for antibodies (0.73 nM). Benefiting from strong NPs-protein interactions, the same particles are also effective against other strains of coronaviruses, such as HCoV-HKU1, HCoV-OC43, HCoV-NL63, and SARS-CoV-2 Omicron variants with IC50 values below 10 pM (21.8 ng/mL). Considering rapid response to outbreaks, exposure to elevated temperatures causes no change in the antiviral activity of NPs while antibodies are completely deactivated. Testing in mice indicates that the chirality-optimized NPs can serve as thermally stable analogs of antiviral biologics complementing the current spectrum of treatments.

Tri-mode Responses to Reactive Oxygen Species In Vivo by Chiral Vanadium-Based Nanoparticles.

Reactive oxygen species (ROS) are closely associated with the redox balance of the physiological environment, and monitoring ROS can aid in the early diagnosis of many diseases, including cancer. In this study, chiral vanadium trioxide/vanadium nitride (V2O3/VN) nanoparticles (NPs) modified with an organic dye (cyanine 3 [Cy3]) were prepared for ROS sensing. Chiral V2O3/VN NPs were prepared with the "ligand-induced chirality" strategy and showed a g-factor of up to 0.12 at a wavelength of 512 nm. To the best of our knowledge, this g-factor is the highest value of all chiral ceramic nanomaterials. The very high g-factor of the nanoprobe confers very high sensitivity, because the higher g-factor, the higher sensitivity. In the presence of ROS, V3+ in the chiral V2O3/VN nanoprobe undergoes a redox reaction to form V2O5, reducing the circular dichroism and absorbance signals, whereas the fluorescence signal of Cy3 is restored. With this nanoprobe, the limits of detection for the circular dichroic and fluorescence signals in living cells are 0.0045 nmol/106 and 0.018 nmol/106 cells, respectively. This chiral nanoprobe can also monitor ROS levels in vivo by fluorescence. This strategy provides an innovative approach to the detection of ROS and is expected to promote the wider application of chiral nanomaterials for biosensing.

Recent Progress in Detecting Enantiomers in Food.

The analysis of enantiomers in food has significant implications for food safety and human health. Conventional analytical methods employed for enantiomer analysis, such as gas chromatography and high-performance liquid chromatography, are characterized by their labor-intensive nature and lengthy analysis times. This review focuses on the development of rapid and reliable biosensors for the analysis of enantiomers in food. Electrochemical and optical biosensors are highlighted, along with their fabrication methods and materials. The determination of enantiomers in food can authenticate products and ensure their safety. Amino acids and chiral pesticides are specifically discussed as important chiral substances found in food. The use of sensors replaces expensive reagents, offers real-time analysis capabilities, and provides a low-cost screening method for enantiomers. This review contributes to the advancement of sensor-based methods in the field of food analysis and promotes food authenticity and safety.

Interfacial Self-assembly of Chiral Selenide Nanomembrane for Enantiospecific Recognition.

Here, we report the synthesis of chiral selenium nanoparticles (NPs) using cysteine and the interfacial assembly strategy to generate a self-assembled nanomembrane on a large-scale with controllable morphology and handedness. The selenide (Se) NPs exhibited circular dichroism (CD) bands in the ultraviolet and visible region with a maximum intensity of 39.96 mdeg at 388 nm and optical anisotropy factors (g-factors) of up to 0.0013 while a self-assembled monolayer nanomembrane exhibited symmetrical CD approaching 72.8 mdeg at 391 nm and g-factors up to 0.0034. Analysis showed that a photocurrent of 20.97±1.55 nA was generated by the D-nanomembrane when irradiated under light while the L-nanomembrane generated a photocurrent of 20.58±1.36 nA. Owing to the asymmetric intensity of the photocurrent with respect to the handedness of the nanomembrane, an ultrasensitive recognition of enantioselective kynurenine (Kyn) was achieved by the ten-layer (10L) D-nanomembrane exhibiting a photocurrent for L-kynurenine (L-Kyn) that was 8.64-fold lower than that of D-Kyn, with a limit of detection (LOD) of 0.0074 nM for the L-Kyn, which was attributed to stronger affinity between L-Kyn and D-Se NPs. Noticeably, the chiral Se nanomembrane precisely distinguished L-Kyn in serum and cerebrospinal fluid samples from Alzheimer's disease patients and healthy subjects.

Ultrasmall Magneto-chiral Cobalt Hydroxide Nanoparticles Enable Dynamic Detection of Reactive Oxygen Species in Vivo.

Biological application of chiral nanoparticles (NPs) has aroused enormous levels of attention over recent years. Here, we synthesized magneto-chiral cobalt hydroxide (Co(OH)2) NPs that exhibited strong chiroptical and unique magnetic properties and applied these NPs to detect and monitor reactive oxygen species (ROS) in living cells and in vivo. Circular dichroism (CD) and magnetic resonance imaging (MRI) signals of the magneto-chiral Co(OH)2 NPs exhibited a wide intracellular ROS detection range from 0.673 to 612.971 pmol/106 cells with corresponding limits of detection (LOD) at 0.087 and 0.179 pmol/106 cells, far below that of currently available probes; the LOD for d-aspartic acid coated Co(OH)2 NPs (d-Co(OH)2 NPs) was 5.7 times lower than that for l-aspartic acid coated Co(OH)2 NPs (l-Co(OH)2 NPs) based on the CD signals. In addition, d-Co(OH)2 NPs also exhibited dynamic ROS monitoring ability. The high levels of selectivity and sensitivity to ROS in complex biological environments can be attributed to the Co2+ oxidation reaction on the surface of the NPs. Furthermore, magneto-chiral Co(OH)2 NPs were able to quantify the levels of ROS in living mice by fluorescence and MRI signals. Collectively, these results reveal that magneto-chiral Co(OH)2 NPs exhibit a remarkable ability to quantify ROS levels in living organisms, and could therefore provide new tools for exploring chiral nanomaterials as a potential biosensor to investigate biological events.

Six-Pointed Star Chiral Cobalt Superstructures with Strong Antibacterial Activity.

Chiral inorganic nanomaterials have shown promise as a potential means of combating bacteria due to their high levels of biocompatibility, easy surface modification, and excellent optical properties. In this study, a diverse range of chiral hierarchical nanomaterials are prepared from Co2+ and L/D-Tartaric acid (Tar) ligands. By combining the ligands in different ratios, chiral Co superstructures (Co SS) are obtained with different morphologies, including chiral nanoflowers, chiral nanohanamaki, a chiral six-pointed star, a chiral fan shape, and a chiral fusiform shape. It is found that the chiral six-pointed star structures exhibit chiroptical activity across a broad range of wavelengths from 300 to 1300 nm and that the g-factor is as high as 0.033 with superparamagnetic properties. Under the action of electromagnetic fields, the chiral six-pointed star Co SS shows excellent killing ability against Gram-positive Staphylococcus aureus (ATCC 25923). Compared to L-Co SS, D-Co SS shows stronger levels of antibacterial ability. It is found that the levels of reactive oxygen species generated by D-Co SS are 1.59-fold higher than L-Co SS which is attributed to chiral-induced spin selectivity effects. These findings are of significance for the further development of chiral materials with antibacterial properties.

Chiral-Solvent-Mediated Manganese-Based Hierarchical Supraparticles with Chiroptical Activity.

In this study, manganese-based multiply hierarchical chiral supraparticles (SPs), with an anisotropy factor (g-factor) of 0.102 and circular dichroism (CD) intensity of 260 mdeg at 530 nm, are successfully synthesized with polar-solvent-mediated strategies. Notably, the g-factor of the SPs is further enhanced to 0.121 by the addition of an external chiral solvent, generating a chiral biased environment, which increases their CD intensity to 320 mdeg at 500 nm. The mechanism underlying the different chirality is proposed to be a difference in the angle of tilt of ±33° between the two enantiomers of the chiral SPs, which involves a difference of ±7° between the orientation of individual nanoplatelets. Chiral solvents induce the angle between adjacent nanoplatelets to get smaller than the original structure that leads to their higher anisotropic value. These findings potentially provide a practical method for the construction of complex chiral superstructures and the regulation of chiroptical activity.

Quantitative zeptomolar imaging of miRNA cancer markers with nanoparticle assemblies.

Multiplexed detection of small noncoding RNAs responsible for posttranscriptional regulation of gene expression, known as miRNAs, is essential for understanding and controlling cell development. However, the lifetimes of miRNAs are short and their concentrations are low, which inhibits the development of miRNA-based methods, diagnostics, and treatment of many diseases. Here we show that DNA-bridged assemblies of gold nanorods with upconverting nanoparticles can simultaneously quantify two miRNA cancer markers, namely miR-21 and miR-200b. Energy upconversion in nanoparticles affords efficient excitation of fluorescent dyes via energy transfer in the superstructures with core-satellite geometry where gold nanorods are surrounded by upconverting nanoparticles. Spectral separation of the excitation beam and dye emission wavelengths enables drastic reduction of signal-to-noise ratio and the limit of detection to 3.2 zmol/ngRNA (0.11 amol or 6.5 × 104 copies) and 10.3 zmol/ngRNA (0.34 amol or 2.1 × 105 copies) for miR-21 and miR-200b, respectively. Zeptomolar sensitivity and analytical linearity with respect to miRNA concentration affords multiplexed detection and imaging of these markers, both in living cells and in vivo assays. These findings create a pathway for the creation of an miRNA toolbox for quantitative epigenetics and digital personalized medicine.

Chiral Self-Assembled Film from Semiconductor Nanorods with Ultra-Strong Circularly Polarized Luminescence.

Chiroptical nanomaterials have generated significant levels of interest for generating strong circularly polarized luminescence (CPL) signals. We used the Langmuir-Schaeffer technique to generate the continuous and compact assembly of CdSe/CdS chiral film. We assembled achiral CdSe/CdS nanorods by controlling the number of layers and angles between different layers. This allowed us to tailor chiroptical properties to achieve high CPL signals. The chiral film was symmetrical and had the highest circular dichroism (CD) response and CPL signals with ten layers (RH (right-handed)-/LH (left-handed)-5 + 5 layers) and a 45° inter-angle. Specifically, RH-5+5 of the chiral film exhibited 1431 mdeg of CD activity and strong CPL signals with a dissymmetry factor (glum) of 0.0997. The helical stacked crystal plates with linear birefringence resulted in strong circular birefringence, as determined by the Reusch model. Electromagnetic simulations indicated that such remarkable optical activity was attributed to the birefringence and dichroism of the well-aligned CdSe/CdS nanorod layers in the chiral films. Under right/left circular polarized (RCP/LCP) light excitation, the well aligned semiconductor nanorods exhibited differences in the coupling efficiencies to RCP and LCP light. Our CdSe/CdS chiral films, which exhibit ultra-strong CPL activity, will provide a novel strategy for the fabrication of chiroptical devices.

Tailored Chiral Copper Selenide Nanochannels for Ultrasensitive Enantioselective Recognition and Detection.

We constructed a tailorable membrane channel system consisting of penicillamine molecules intercalated in copper selenide nanoparticles (Cu2-x Se NPs), which exhibited circular dichroism (CD) bands in the near infrared region (CD, 800-1600 nm) with a maximum intensity of 164.5 mdeg at 1440 nm. The chiral ligand hybridized to the surface of achiral Cu2-x Se NPs by breaking the intrinsic symmetry of Cu2-x Se NPs and further large-scale assembly induced strong optical activity. The fabricated multilayer chiral membrane achieved an increased rectification ratio (RR) up to 114. The integration of penicillamine allowed for high enantioselective recognition against naproxen,which displayed high sensitivity with a limit of detection (LOD) as low as 0.027 nM.

Improved Reactive Oxygen Species Generation by Chiral Co3 O4 Supraparticles under Electromagnetic Fields.

One of the most common methods to treat thromboembolism is the use of thrombolytic drugs to activate fibrinolytic protease. The aim of this treatment was to initiate the lysis of fibrin; however, there are many side-effects associated with this form of treatment. Herein, we fabricated chiral Co3 O4 supraparticles (SPs) with a g-factor of up to 0.02 at 550 nm and paramagnetic performance applied in the treatment of thromboembolism under an electromagnetic field (MF). In vitro experiments showed that d-SPs degraded blood clot within 8 hours under MF. Compared to l-SPs, d-SPs exhibited much stronger thrombolytic ability and effectively enhanced the survival rate of thrombosis model mice more than 70 % in the 25 d of observation. The results of mechanism study showed that under MF, the level of reactive oxygen species (ROS) produced by d-SPs were 1.5 times higher than that of l-SPs, which might be attributed to the chiral-induced spin selectivity effects.

Chiromagnetic Plasmonic Nanoassemblies with Magnetic Field Modulated Chiral Activity.

Chiral plasmonic nanoassemblies, which exhibit outstanding chiroptical activity in the visible or near-infrared region, are popular candidates in molecular sensing, polarized nanophotonics, and biomedical applications. Their optical chirality can be modulated by manipulating chemical molecule stimuli or replacing the building blocks. However, instead of irreversible chemical or material changes, real-time control of optical activity is desired for reversible and noninvasive physical regulating methods, which is a challenging research field. Here, the directionally and reversibly switching optical chirality of magneto-plasmonic nanoassemblies is demonstrated by the application of an external magnetic field. The gold-magnetic nanoparticles core-satellite (Au@Fe3 O4 ) nanostructures exhibit chiral activity in the UV-visible range, and the circular dichroism signal is 12 times greater under the magnetic field. Significantly, the chiral signal can be reversed by regulating the direction of the applied magnetic field. The attained magnetic field-regulated chirality is attributed to the large contributions of the magnetic dipole moments to polarization rotation. This magnetic field-modulated optical activity may be pivotal for photonic devices, information communication, as well as chiral metamaterials.

Light-Induced Chiral Iron Copper Selenide Nanoparticles Prevent ß-Amyloidopathy In†Vivo.

The accumulation and deposition of ß-amyloid (Aß) plaques in the brain is considered a potential pathogenic mechanism underlying Alzheimer's disease (AD). Chiral l/d-Fex Cuy Se nanoparticles (NPs) were fabricated that interfer with the self-assembly of Aß42 monomers and trigger the Aß42 fibrils in dense structures to become looser monomers under 808 nm near-infrared (NIR) illumination. d-Fex Cuy Se NPs have a much higher affinity for Aß42 fibrils than l-Fex Cuy Se NPs and chiral Cu2-x Se NPs. The chiral Fex Cuy Se NPs also generate more reactive oxygen species (ROS) than chiral Cu2-x Se NPs under NIR-light irradiation. In living MN9D cells, d-NPs attenuate the adhesion of Aß42 to membranes and neuron loss after NIR treatment within 10 min without the photothermal effect. In-vivo experiments showed that d-Fex Cuy Se NPs provide an efficient protection against neuronal damage induced by the deposition of Aß42 and alleviate symptoms in a mouse model of AD, leading to the recovery of cognitive competence.

Chiral Cux Coy S Nanoparticles under Magnetic Field and NIR Light to Eliminate Senescent Cells.

In the present study, chiral Cux Coy S nanoparticles (NPs) were developed to selectively induce apoptosis of senescent cells using both an alternating magnetic field (AMF) and near infrared (NIR) photon illumination. The chiral effects on living cells were investigated, and d-Cux Coy S NPs showed about 2.5 times higher of internalized ability than l-NPs. By modifying beta 2 macroglobulin (MG), senescent cells were effectively eliminated by d-Cux Coy S NPs without damaging the activities of normal cells under AMF and photon illumination. Compared to the individual application of NIR illumination and AMF, their synergistic effect induced the production of caspase-3 with a much shorter treatment time and higher efficiency due to the more serious photon-induced cellular redox and mechanical damage of cellular skeleton. Moreover, the developed strategy was successfully used to remove senescent cells in vivo. This study developed a controllable way of regulating cell activities using chiral NPs, which will provide a valuable way for treating diseases and promoting health.

Chiral Molecule-mediated Porous Cu xO Nanoparticle Clusters with Antioxidation Activity for Ameliorating Parkinson's Disease.

Reactive oxygen species (ROS)-mediated mitochondrial dysfunction is one of the major pathological mechanisms of Parkinson's disease. Using inorganic nanomaterials to scavenge ROS has drawn significant interest and can prevent ROS-mediated neurological disorders. We prepared uniform Cu xO nanoparticle clusters (NCs) with an average size of 65 ± 7 nm, using phenylalanine (Phe) as the structure-directing agent. These Cu xO NCs functionally mimicked the activities of peroxidase, superoxide dismutase, catalase, and glutathione peroxidase. Because they eliminated ROS, the Cu xO NCs inhibited neurotoxicity in a cellular model of Parkinson's disease and rescued the memory loss of mice with Parkinson's disease. The biocompatibility and multiple enzyme-mimicking activities of Cu xO NCs offer new opportunities for the application of NCs in biomedicine, biosensing, and biocatalysis.

Chiral Core-Shell Upconversion Nanoparticle@MOF Nanoassemblies for Quantification and Bioimaging of Reactive Oxygen Species in Vivo.

In this study, a hybrid nanoassembly consisting of an upconversion nanoparticle (UCNP) core and a zeolitic imidazolate framework-8 (ZIF) shell encapsulated with chiral NiSx NPs (denoted as UCNP@ZIF-NiSx) were fabricated. The UCNP@ZIF-NiSx nanoassemblies showed an intense circular dichroism (CD) signal at 440 and 530 nm, whereas the upconversion luminescence (UCL) signal of the UCNPs at 540 nm were quenched by NiSx NPs and the UCL signal at 660 nm was almost unchanged. By taking advantage of the chiral-optical and fluorescent signals, the dual mode nanoassemblies can be used for quantitively monitoring reactive oxygen species (ROS), with hydrogen peroxide (H2O2) as the proof-of-concept target in living cells. The experimental results revealed that UCNP@ZIF-NiSx has been changed into UCNP@ZIF with degradation of NiSx during the detection process. Noticeably, quantitative and selective detection of ROS was successfully carried out in vivo. This strategy highlights the potential of chiral nanoassemblies for ROS detection, which opens up a new avenue to develop the toolbox of chiral nanomaterials for biomedical and biological analysis.

Au@gap@AuAg Nanorod Side-by-Side Assemblies for Ultrasensitive SERS Detection of Mercury and its Transformation.

As one of the most toxic heavy metal elements, mercury ion (Hg2+ ) and its methylated product, methylmercury (MeHg) can pose a threat to human health and the environment. Herein, a novel Raman biosensor with cascade sensitivity is developed for Hg2+ detection through Au@gap@AuAg nanorod side-by-side assemblies. Due to the strong electromagnetic coupling from the assemblies and core-shell structure, the Raman sensor possesses high sensitivity with the limit of detection (LOD) of 0.001 ng mL-1 , which is about one order lower than traditional atomic fluorescence spectrometer (AFS) methods. Moreover, the fabricated biosensor is used to measure residual mercury levels in tissues and eggs of hens fed high-mercury diets, and the results show total mercury in collected egg yolks is 20 times higher than whites. Furthermore, the form of mercury in the eggs is also analyzed by high-performance liquid chromatography coupled with AFS, and, unexpectedly, the methylated product MeHg tends to only be found in egg whites. These interesting differences may indicate a new research direction for the toxicity of mercury in living organisms, and the developed ultrasensitive Surface Enhanced Raman Scattering (SERS) method could pave a broad way for the application of biosensors in Hg detection.

An Ultrasensitive Electrochemical Immunosensor for Nonylphenol Leachate from Instant Noodle Containers in Southeast Asia.

Nonylphenols (NPNs) are persistent endocrine disruptors and their release into the environment is causing increasing concern about their impact on human health. Herein, an ultrasensitive electrochemical immunosensor was developed for the detection of NPNs in the leachates from 61 instant noodle containers (INCs) from 8 countries across Southeast Asia. Gold nanoclusters (AuNCs) were self-assembled with reduced graphene oxide (rGO; polyethylenimine-rGO) and used to modify a glassy carbon electrode (GCE), which showed excellent electrical conductivity. An anti-NPN antibody was then immobilized on the AuNCs and, if it specifically bound NPN, the reduction in conductivity of the GCE was remarkable. The designed immunosensor has a low detection limit (5.25 ng L-1 ) and high sensitivity for NPNs in the leachates of INCs. Remarkably, the leaching of estrogen-like compounds from different plastics of INCs and the correlation between NPN content and total estrogenic activity were thoroughly investigated. High temperatures caused polyethylene and polystyrene INCs to release more estrogen-like compounds than that of polypropylene INCs; this increased release of NPNs was associated with higher estrogen activity in living cells. These data fill the gap in human and environmental exposure to estrogen-like compounds through INCs.

Circularly Polarized Light Triggers Biosensing Based on Chiral Assemblies.

Chiral assemblies have attracted great interest because of their many potential applications, such as in chiral sensing, asymmetric catalysis, and optical devices. Here, by using specific DNAzymes, a chiral core-satellite assembly consisting of a DNAzyme-driven spiny nanorod dimer core and upconversion nanoparticle (UCNP) satellite was constructed. The chirality of this assembly originates from the geometry chirality. This chiral assembly can be used as a photothermally activated probe for the simultaneous detection of multiple analytes in living cells. Under illumination with 980 nm left circularly polarized (LCP) light, this probe was used to quantify and visualize intracellular metal ions.