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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 ROSmediated neurological disorders. We prepared uniform Cu x O nanoparticle clusters (NCs) with an average size of 65 ± 7 nm, using phenylalanine (Phe) as the structure-directing agent. These Cu x O NCs functionally mimicked the activities of peroxidase, superoxide dismutase, catalase, and glutathione peroxidase. Because they eliminated ROS, the Cu x O 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 x O NCs offer new opportunities for the application of NCs in biomedicine, biosensing, and biocatalysis.

Gene editing is an important genetic engineering technique that enables gene manipulation at the molecular level. It mainly relies on engineered nucleases of biological origin, whose precise functions cannot be replicated in any currently known abiotic artificial material. Here, we show that chiral cysteine-modified CdTe nanoparticles can specifically recognize and, following photonic excitation, cut at the restriction site GAT'ATC (' indicates the cut site) in double-stranded DNA exceeding 90 base pairs, mimicking a restriction endonuclease. Although photoinduced reactive oxygen species are found to be responsible for the cleavage activity, the sequence selectivity arises from the affinity between cysteine and the conformation of the specific DNA sequence, as confirmed by quantum-chemical calculations. In addition, we demonstrate non-enzymatic sequence-specific DNA incision in living cells and in vivo using these CdTe nanoparticles, which may help in the design of abiotic materials for gene editing and other biological applications.

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The accumulation and deposition of β‐amyloid (Aβ) plaques in the brain is considered a potential pathogenic mechanism underlying Alzheimer's disease (AD). Chiral l/d‐FexCuySe nanoparticles (NPs) were fabricated that interfer with the self‐assembly of Aβ42 monomers and trigger the Aβ42 fibrils in dense structures to become looser monomers under 808 nm near‐infrared (NIR) illumination. d‐FexCuySe NPs have a much higher affinity for Aβ42 fibrils than l‐FexCuySe NPs and chiral Cu2−xSe NPs. The chiral FexCuySe NPs also generate more reactive oxygen species (ROS) than chiral Cu2−xSe NPs under NIR‐light irradiation. In living MN9D cells, d‐NPs attenuate the adhesion of Aβ42 to membranes and neuron loss after NIR treatment within 10 min without the photothermal effect. In‐vivo experiments showed that d‐FexCuySe NPs provide an efficient protection against neuronal damage induced by the deposition of Aβ42 and alleviate symptoms in a mouse model of AD, leading to the recovery of cognitive competence.

The interactions between chiral nanomaterials and organisms are still challenging and mysterious. Here, a chiral nanodevice made of yolk–shell nanoparticles tetrahedron (UYTe), centralized with upconversion nanoparticles (UCNPs), was fabricated to induce autophagy in vivo. The proposed chiral nanodevice displayed a tunable circular dichroism (CD) signal when modified with different enantiomers of glutathione (GSH). Notably, UYTe showed significant chirality-dependent autophagy-inducing ability after d-GSH-modification because the enhanced oxidative stress and accumulation in living cell. The activation of autophagy resulted in the reduced intracellular CD intensity from the disassembly of the structure. The intracellular ATP concentration was simultaneously enhanced in response to autophagy activity, which was quantitatively bio-imaged with the upconversion luminescence (UCL) signal of the UCNP that escaped from UYTe. The autophagy effect induced in vivo by the chiral UYTe was also visualized with UCL imaging, demonstrating the great potential utility of the chiral nanostructure for cellular biological applications.

Chiral plasmonic nanomaterials have attracted unprecedented attention due to their broad applications in biomedicine, negative refractive index, and chiral sensing. Here, using a wet‐chemistry process, chiral triangular Au nanorings are fabricated with a platinum (Pt) framework (l/d‐Pt@Au triangular nanorings, named l/d‐Pt@Au TNRs). The l/d‐Pt@Au TNRs exhibit strong optical activity with a g‐factor of 0.023 and can be used effectively for the discrimination of enantiomers due to selective resonance coupling between the induced electric and magnetic dipoles associated with enantiomers and the chiral plasmonic TNRs, also known as the surface‐enhanced Raman scattering‐chiral anisotropy (SERS‐ChA) effect. The chiral d‐Pt@Au TNRs represent a label‐free SERS platform that can be applied to detect Aβ monomers and fibrils, the hallmarks of Alzheimer's disease (AD), achieving a limit of detection (LOD) down to 0.045 × 10−12 m and 4 × 10−15 m for 42‐residue‐long amyloid‐β (Aβ42) monomer and fibrils, respectively. Furthermore, chiral d‐Pt@Au TNRs can also be successfully carried out to detect Aβ42 proteins in AD patients with ultrahigh levels of sensitivity, thus allowing picogram quantities of Aβ42 proteins to be identified. This research opens up an avenue for the use of chiral plasmonic nanomaterials as ultrasensitive SERS substrates to early diagnosis of protein‐misfolding diseases.

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.