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.

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.

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.

Mitochondria-Targeting Plasmonic Spiky Nanorods Increase the Elimination of Aging Cells in Vivo.

Cellular senescence is stress-induced, irreversible growth arrest, and is thought to impair tissue function. The clearance of senescent cells can delay the features of senescence. Herein, we report the development of plasmonic core-shell spiky nanorods (CSNRs) surface-modified with an anti-beta-2-microglobulin (aB2MG) antibody and triphenylphosphonium (TPP), to target the mitochondria in senescent cells. aB2MG-TPP@CSNRs irradiated with near-infrared (NIR) light selectively caused mitochondrial damage and apoptosis of senescent cells with relatively low NIR light power, and the ability of CSNRs to activate and amplify the immune response in vitro and in vivo was discovered. The photo-induced generation of reactive oxygen species (ROS) resulted in senescent-cell apoptosis and immune adjuvant effect by CSNRs accelerated the clearance of senescent cells in mice. This study opens the way for the use of precisely regulated plasmonic nanostructures for immune adjuvant and photo-induced apoptosis for age-related senescence.

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.

Photoinduced elimination of senescent microglia cells in vivo by chiral gold nanoparticles.

Parkinson's disease (PD) is an age-related neurodegenerative disease, and the removal of senescent cells has been proved to be beneficial for improving age-associated pathologies in neurodegeneration disease. In this study, chiral gold nanoparticles (NPs) with different helical directions were synthesized to selectively induce the apoptosis of senescent cells under light illumination. By modifying anti-B2MG and anti-DCR2 antibodies, senescent microglia cells could be cleared by chiral NPs without damaging the activities of normal cells under illumination. Notably, l-P+ NPs exhibited about a 2-fold higher elimination efficiency than d-P- NPs for senescent microglia cells. Mechanistic studies revealed that the clearance of senescent cells was mediated by the activation of the Fas signaling pathway. The in vivo injection of chiral NPs successfully confirmed that the elimination of senescent microglia cells in the brain could further alleviate the symptoms of PD mice in which the alpha-synuclein (α-syn) in cerebrospinal fluid (CFS) decreased from 83.83 ± 4.76 ng mL-1 to 8.66 ± 1.79 ng mL-1 after two months of treatment. Our findings suggest a potential strategy to selectively eliminate senescent cells using chiral nanomaterials and offer a promising strategy for alleviating PD.

Facet-Dependent Biodegradable Mn3 O4 Nanoparticles for Ameliorating Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegeneration disease. Unfortunately, there are no effective measures to prevent or inhibit this disease. In this study, biodegradable Mn3 O4 nanoparticles (NPs) in different shapes are prepared and enclosed them by {100}, {200} and {103} facets that exhibit facet-dependent protection against neurotoxicity induced by oxidative damage in a cell model of PD. Notably, Mn3 O4 nanorods enclosed by {103} facets exhibit high levels of enzyme-like activity to eliminate reactive oxygen specie in vitro. It is also determined that the uptake pathway of Mn3 O4 NPs into MN9D cells is mediated by caveolin. The data demonstrate that Mn3 O4 nanorods can be taken up by cells effectively and confer excellent levels of neuroprotection while the biodegradation of Mn3 O4 NPs in vivo is confirmed by photoacoustic image of Mn3 O4 NPs in brain at 60 d. Furthermore, the oxygen scavenging effect created by Mn3 O4 nanorods is successfully applied to a mouse model of PD; the amount of α-synuclein in the cerebrospinal fluid of PD mice is reduced by 61.2% in two weeks, thus demonstrating the potential application of facet-directed Mn3 O4 NPs for the clinical therapy of neurodegenerative disease.