Chiral Intranasal Nanovaccines as Antivirals for Respiratory Syncytial Virus.

This study aimed to develop an intranasal nanovaccine by combining chiral nanoparticles with the RSV pre-fusion protein (RSV protein) to create L-nanovaccine (L-Vac). The results showed that L-NPs increased antigen attachment in the nasal cavity by 3.83 times and prolonged its retention time to 72 h. In vivo experimental data demonstrated that the intranasal immunization with L-Vac induced a 4.86-fold increase in secretory immunoglobulin A (sIgA) secretion in the upper respiratory tract, a 1.85-fold increase in the lower respiratory tract, and a 20.61-fold increase in RSV-specific immunoglobin G (IgG) titer levels in serum, compared with the commercial Alum Vac, while the neutralizing activity against the RSV authentic virus is 1.66-fold higher. The mechanistic investigation revealed that L-Vac activated the tumor necrosis factor (TNF) signaling pathway in nasal epithelial cells (NECs), in turn increasing the expression levels of interleukin-6 (IL-6) and C-C motif chemokine ligand 20 (CCL20) by 1.67-fold and 3.46-fold, respectively, through the downstream nuclear factor kappa-B (NF-κB) signaling pathway. Meanwhile, CCL20 recruited dendritic cells (DCs) and L-Vac activated the Toll-like receptor signaling pathway in DCs, promoting IL-6 expression and DCs maturation, and boosted sIgA production and T-cell responses. The findings suggested that L- Vac may serve as a candidate for the development of intranasal medicine against various types of respiratory infections.

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.

Chiral Nanomaterials for Cancer Vaccines.

Chirality is a fundamental characteristic of living organisms and is commonly observed at the biomolecule, cellular, and tissue levels. Chiral nanomaterials play an irreplaceable role in nanomedicine and nanobiology because of their unique enantioselectivity with biological components. Here, research progress relating to chiral nanomaterials in the field of vaccines is reviewed, including antigen presenting systems, immune adjuvants, and cancer vaccines. First, the common synthesis methods are outlined for different types of chiral nanomaterials, as well as their chiral sources, optical properties, and potential biological applications. Then, the application of chiral nanomaterials are discussed in the field of vaccines with reference to the promotion of antigen presentation and activation of the immune system for tumor immunotherapy. Finally, the current obstacles and future research directions of chiral nanomaterials are revealed with regard to regulating the immune system.

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.

Chiral Iron Oxide Supraparticles Enable Enantiomer-Dependent Tumor-Targeted Magnetic Resonance Imaging.

The chemical, physical and biological effects of chiral nanomaterials have inspired general interest and demonstrated important advantages in fundamental science. Here, chiral iron oxide supraparticles (Fe3 O4 SPs) modified by chiral penicillamine (Pen) molecules with g-factor of ≈2 × 10-3 at 415 nm are fabricated, and these SPs act as high-quality magnetic resonance imaging (MRI) contrast agents. Therein, the transverse relaxation efficiency and T2 -MRI results demonstrated chiral Fe3 O4 SPs have a r2 relaxivity of 157.39 ± 2.34 mM-1 ·S-1 for D-Fe3 O4 SPs and 136.21 ± 1.26 mM-1 ·S-1 for L-Fe3 O4 SPs due to enhanced electronic transition dipole moment for D-Fe3 O4 SPs compared with L-Fe3 O4 SPs. The in vivo MRI results show that D-Fe3 O4 SPs exhibit two-fold lower contrast ratio than L-Fe3 O4 SPs, which enhances targeted enrichment in tumor tissue, such as prostate cancer, melanoma and brain glioma tumors. Notably, it is found that D-Fe3 O4 SPs have 7.7-fold higher affinity for the tumor cell surface receptor cluster-of-differentiation 47 (CD47) than L-Fe3 O4 SPs. These findings uncover that chiral Fe3 O4 SPs act as a highly effective MRI contrast agent for targeting and imaging broad tumors, thus accelerating the practical application of chiral nanomaterials and deepening the understanding of chirality in biological and non-biological environments.

A colloidal gold immunoassay strip assay for cadmium detection in oilfield chemicals.

Cadmium ions (Cd2+) are some of the major pollutants in oilfield chemicals. To reduce the pollution of oilfield chemicals, it is necessary to detect and control the content of Cd2+. In this study, we synthesized a highly sensitive and specific monoclonal antibody against Cd2+ with an IC50 of 1.97 ng mL-1 and no cross-reactivity. Based on this antibody, a colloidal gold immunoassay strip detection assay with an IC50 of 1 mg kg-1 and a detection range of 1.0-20 mg kg-1 in oilfield chemicals was developed. This assay could be completed in 20 min and can be used for Cd2+ on-site testing in oilfield chemicals and improve supervision efficiency in oil exploration and development.

Chiral Se@CeO2 superparticles for ameliorating Parkinson's disease.

In this study, we prepare chiral D-/L-type Se@CeO2 superparticles (D-/L-SPs) with a g-factor of 0.018 using D-/L-cysteine as chiral ligands. The chiral SPs demonstrate ultra-high enzyme activity of peroxidase (POD), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Due to the synergistic effect between Se and CeO2, the maximum initial velocity of GPx, CAT, and POD for L-SP is 10, 7, and 5.6 times higher than that of a mixture of Se nanoparticles (NPs) and CeO2 NPs. Significantly, the chiral L-SPs show much stronger ROS scavenging ability than D-SP in the PD-like cell model. Moreover, the amount of α-synuclein (α-syn) in the cerebrospinal fluid of PD mice is reduced by 70.7% within two weeks. The L-SPs effectively alleviate neurodegeneration in a mouse model of PD, showing potential applications in the clinical treatment of neurodegenerative diseases.

Development of a colloidal gold immunochromatographic strip for rapid and sensitive detection of nicotine.

Nicotine (NCT) is commonly contained in e-cigarette oils, and long-term nicotine intake can exacerbate cardiovascular disease, neurodegenerative disease, and lung cancer. Therefore, there is a need to develop a fast and sensitive method for detecting NCT in e-cigarette oils. We prepared anti-NCT monoclonal antibodies (mAbs), which belong to the IgG2 subclass. The optimum mAb had a half-maximal inhibitory concentration (IC50) of 6.81 ng/mL for NCT. We developed a colloidal gold immunochromatographic strip (CG-ICS) to detect NCT content with a visual cut-off and limit of detection of 20 ng/mL and 0.40 ng/mL, respectively. The recovery rates of NCT from spiked samples ranged between 100.36% and 109.96% based on CG-ICS. These results were consistent with those obtained from high performance liquid chromatography (HPLC). We confirmed the reliability of CG-ICS using NCT-positive samples. Therefore, CG-ICS represents an effective and rapid on-site screening tool for the detection of NCT in e-cigarette oils.

Chiral MoSe2 Nanoparticles for Ultrasensitive Monitoring of Reactive Oxygen Species In Vivo.

Reactive oxygen species (ROS) are involved in neurodegenerative diseases, cancer, and acute hepatitis, and quantification of ROS is critical for the early diagnosis of these diseases. In this work, a novel probe is developed, based on chiral molybdenum diselenide (MoSe2 ) nanoparticles (NPs) modified by the fluorescent molecule, cyanine 3 (Cy3). Chiral MoSe2 NPs show intensive circular dichroism (CD) signals at 390 and 550 nm, whereas the fluorescence of Cy3 at 560 nm is quenched by MoSe2 NPs. In the presence of ROS, the probe reacts with the ROS and then oxidates rapidly, resulting in decreased CD signals and the recovery of the fluorescence. Using this strategy, the limit of detection values of CD and fluorescent signals in living cells are 0.0093 nmol/106 cells and 0.024 nmol/106 cells, respectively. The high selectivity and sensitivity to ROS in complex biological environments is attributed to the Mo4+ and Se2- oxidation reactions on the surface of the NPs. Furthermore, chiral MoSe2 NPs are able to monitor the levels of ROS in vivo by the fluorescence. Collectively, this strategy offers a new approach for ROS detection and has the potential to inspire others to explore chiral nanomaterials as biosensors to investigate biological events.

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.

Development of a colloidal gold strip assay for the detection of total homocysteine in serum samples.

Homocysteine (Hcy) is an amino acid found in the human body and has the potential to predict cardiovascular risk where timely detection and treatment are very important. In this study, we established a method to combine enzymatic hydrolysis with a colloidal gold lateral flow immunoassay (LFIA) for the detection of total Hcy (tHcy) based on the monoclonal antibody (mAb) 3B3 against S-adenosyl-L-homocysteine (SAH). The 50% inhibitory concentration (IC50) for this mAb against SAH was 2.94 nM with a linear range of 0.73-11.75 nM. The developed LFIA could detect SAH with a vLOD and cLOD of 10 nM and 2.07 nM, respectively. For tHcy detection in serum samples, the LFIA strip was able to detect tHcy after enzymatic hydrolysis, and the results correlated well with that of an enzymatic cycling test kit.

Rapid and sensitive detection of tert-butylhydroquinone in soybean oil using a gold-based paper sensor.

tert-Butylhydroquinone (TBHQ) residues in foods pose a threat to human health. Therefore, it is necessary to develop a rapid method for TBHQ detection. In this study, a sensitive monoclonal antibody 5C3 (IgG2a subclass) against TBHQ was produced. It possessed a half maximal inhibitory concentration of 7.43 ng mL-1. A gold nanoparticle-based immunochromatographic assay (ICA) was established for the rapid and sensitive screening of TBHQ in soybean oil. Qualitative analysis results were obtained within 10 min and observed with the naked eye. The visual limit of detection (LOD) was 50 ng g-1 and the cut-off value was 1000 ng g-1. A hand-held strip reader was used for quantitative analysis, in which the calculated LOD was defined as 18.68 ng g-1. The average recoveries of TBHQ ranged from 89.55% ± 2.70% to 100.66% ± 3.02% for soybean oil, with a coefficient of variation of 2.89%-7.05%. Therefore, our developed ICA is a useful tool for the rapid and on-site detection of TBHQ in real food samples.

The Development of Chiral Nanoparticles to Target NK Cells and CD8+ T Cells for Cancer Immunotherapy.

The chirality of nanomaterials (nanoparticles, NPs) can influence their interaction with cells and biological systems. However, how chirality can exert impact on the immune response has yet to be investigated. Here, the immunological effect of chiral nanomaterials is investigated as a therapeutic and preventive option against tumors. Compared with achiral nanoparticles, chiral NPs with a g-factor of 0.44 are shown to enhance both innate and acquired immunity against tumor growth. It is also found that chiral NPs enhance the activation of CD8+ T and natural killer cells (CD69+ NK cells) by stimulating dendritic cells (DCs). Importantly, L-type NPs induce a 1.65-fold higher proportion of CD8+ T and CD69+ NK cells than D-type NPs. Next, the therapeutic and preventative effects of chiral NPs against tumors in a EG7.OVA tumor model are investigated. It is found that L-type NPs have a significant greater ability to induce apoptosis in tumor cells and prolong the survival time of model mice than D-type NPs. Mice treated with L-type NPs induce the activation of 84.98 ± 6.63% CD8+ T cells and 33.62 ± 3.41% of NK cells in tumor tissues; these are 1.62-fold and 1.39-fold higher than that seen in the mice treated with D-type NPs. Mechanistic studies reveal that chiral NPs exert mechanical force on bone-marrow-derived dendritic cells (BMDCs) and stimulate the expression of cytokines to induce cytotoxic activity in NK cells. Synergistically, the CD8+ T cells are stimulated to eliminate tumor cells via antigen cross presentation. The force of interaction between L-type NPs and cells is higher than that for D-NPs, thus further promoting the activation of NK cells and CD8+ T cells and their infiltration into tumor tissue. These findings open up a new avenue for chiral nanomaterials to act as immunoadjuvants for the prevention and treatment of cancer.

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.

Ratiometric FRET Encoded Hierarchical ZrMOF @ Au Cluster for Ultrasensitive Quantifying MicroRNA In Vivo.

Here, Zirconium metal-organic frameworks @ gold (ZrMOF @ Au) cluster architectures have been fabricated and then functionalized with two fluorescent dyes (Quasar [QS] and Cyanine5.5 [Cy5.5]) through deoxyribonucleic acid hybridization, to form a fluorescence resonance energy transfer (FRET) encoded ZrMOF  @  Au-QS/Cy5.5 complex. In the presence of the target intracellular microRNA (miR)-21, the fluorescence of Cy5.5 at 705 nm (F705 ) decreases and the fluorescence of QS at 665 nm (F665 ) increases when Cy5.5 is released from the surface of ZrMOF  @  Au-QS/Cy5.5. The change in the fluorescence ratio (F705 /F665 ) shows an outstanding linear range of 0.006-67.9 amol/ngRNA , and the limit of detection is 4.51 zmol/ngRNA in living cells. The high ratio loading of nucleic acid on surface of ZrMOF @ Au cluster and two fluorescence encoded signal enables better sensitivity and reliability. Zeptomolar sensitivity and good linearity against target affords distinct imaging-based monitoring of the cancer marker miR-21 both in living cells and in vivo. At the same time, the architecture displays remarkable photothermal conversion efficiency (53.7%) and gives rise to outstanding therapy ability in vivo. This strategy offers new avenues for the intelligent quantification of miRNAs for simultaneous diagnoses and treatments of early-stage cancers.

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.

Aptamer-Gated Ion Channel for Ultrasensitive Mucin 1 Detection.

Detection of cancer markers is important for early diagnosis and timely treatment of cancer. In this study, we fabricated a tailorable gold nanofilm-anodized aluminum oxide (Au-AAO) ion channel through nanoparticle self-assembly and proposed a highly sensitive and selective Mucin 1 (MUC1) detection method. By engineering the optimal layers of the Au-AAO ion channel and encoding the aptamer between the interlayers, a highly controllable ion rectification phenomenon was observed. From this, the relationship between the rectification ratio (RR) and the concentration of MUC1 was established and the highly sensitive detection of MUC1 is achieved. We found that the aptamer-modified Au-AAO ion channel has a good linear range within the MUC1 concentration of 1-104 fg mL-1 and the limit of detection (LOD) was as low as 0.0364 fg mL-1 (0.0025 aM). Thus, this research opens a new horizon for fabricating multi-functional ion channels as well as developing ultrasensitive detection technologies.

Dual-Modal FexCuySe and Upconversion Nanoparticle Assemblies for Intracellular MicroRNA-21 Detection.

In situ quantification and imaging of low-level intracellular microRNAs (miRs) are important areas in biosensor research. Herein, DNA-driven FexCuySe@upconversion nanoparticle (UCNP) core@satellite nanostructures were developed to probe microRNA-21 (miR-21). FexCuySe@UCNP probes displayed dual signals: upconversion luminescence (UCL) and magnetic resonance imaging (MRI). In the presence of miR-21, the luminescence signal was restored and the T2 value was significantly increased because of dissociation of UCNPs from the assemblies. There was a good linear relationship between the dual signals and the expression levels of miR-21 in the range of 0.035-31.824 amol/ngRNA. The limit of detection (LOD) was 0.0058 amol/ngRNA for the luminescence intensity and 0.0182 amol/ngRNA for the MRI signal. This method opens a new avenue for intracellular miR-21 detection with high sensitivity and specificity.

Correction: SERS- and luminescence-active Au-Au-UCNP trimers for attomolar detection of two cancer biomarkers.

Correction for 'SERS- and luminescence-active Au-Au-UCNP trimers for attomolar detection of two cancer biomarkers' by Aihua Qu et al., Nanoscale, 2017, 9, 3865-3872, DOI: .

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.