Nitric oxide (NO) gas therapy, especially, L-arginine (L-Arg)-based NO treatment strategies have attracted extensive attention in the field of oncotherapy. However, current strategies are unable to differentiate well between normal cells and cancer cells, which may lead to unpredictable toxicity. Motivated by the fact that mitochondria of cancer cells can express excessive nitric oxide synthetase (NOS), herein, a nanozyme-based NO generator, cerium oxide (CeO₂)-AT, is fabricated to specifically catalyze the production of NO in cancer cells for selective tumor treatment. In this system, after being endocytosed into cancer cells, the generator can produce a number of NO under the catalysis of NOS in mitochondria of cancer cells, which can disrupt the mitochondrial respiratory chain of tumor cells and further induce cell apoptosis. In addition, the generator with catalase (CAT)-like activity can catalyze H₂O₂ to produce O₂, which can promote the generation of NO and improve the performance of NO gas therapy. What is more, our system has no obvious impact on the viability of normal cells owing to the less production of NO. Our work paves a new way for the development of highly selective NO-based treatment particularly useful for the safe and specific cancer therapy.

Nanozymes, nanomaterials with enzyme-like activity, have been considered as promising alternatives of natural enzymes. Molecular logic gates, which can simulate the function of the basic unit of an electronic computer, perform Boolean logic operation in response to chemical, biological, or optical signals. Recently, the combination of nanozymes and logic gates enabled bioinformation processing in a logically controllable way. In the review, recent progress in the construction of nanozyme-based logic gates integrated with their utility in sensing is introduced. Furthermore, the issues and challenges in the construction processes are discussed. It is expected the review will facilitate a comprehensive understanding of nanozyme-based logic systems.

Artificial enzymes have provided great antimicrobial activity to combat wound infection. However, the lack of tissue repair capability compromised their treatment effect. Therefore, development of novel artificial enzyme concurrently with the excellent antibacterial activity and the property of promoting wound healing are required. Here, we demonstrated the hydrogel-based artificial enzyme composed of copper and amino acids possessed intrinsic peroxidase-like catalytic activity, which could combat wound pathogen effectively and accelerate wound healing by stimulating angiogenesis and collagen deposition. Furthermore, the system possesses good biocompatibility for practical application. The synergic effect of the hydrogel-based artificial enzyme promises the system as a new paradigm in bacteria-infected wound healing therapy.

Though phytochemicals are a promising alternative to traditional antibiotics for combating resistant bacteria, the low water solubility and lack of selectivity seriously hinder their widespread applications. Herein, we constructed a hyaluronidase-activated "on-demand" delivery nanocarrier to encapsulate plant essential oils (PEOs) for the synergistic treatment of multidrug-resistant bacteria. The bioavailability and selectivity of PEOs was enhanced and the antibacterial effect was significantly improved by combining with the photothermal effect of the nanocarrier. This antibacterial system was successfully applied for healing methicillin-resistant Staphylococcus aureus-infected wound with negligible cytotoxicity and biotoxicity in mice. Given the increasing risk of antibiotic resistance, we believe that this phytochemical-encapsulated nanoplatform would provide a long-term solution and be a new powerful tool for skin-associated bacterial infections.

Silver nanoparticles (AgNPs) with distinct localized surface plasmon resonance (LSPR) absorption spectra can be synthesized using different proteins as templates upon irradiation by light. We utilized the multiple readouts of LSPR signals of AgNPs to construct sensor arrays for pattern recognition of proteins. Room temperature, aqueous solutions, and lack of harsh reducing reagents make the whole process inherently "green". Meanwhile, the strategy efficiently simplified the process of array-receptor preparation and data acquisition, leading to lower time consumption, sample use, and cost. Furthermore, the system can differentiate proteins using flexible and alterable sensor elements by choosing different combinations of LSPR signals at different wavelengths. The principle of the sensor design can also be further extended to differentiate other biomolecules. The study provides a new method to construct feasible, economical, and general nanoparticle-based sensing arrays for pattern recognition.

The aggregation of amyloid-β peptide (Aβ) is implicated in the pathology of Alzheimer's disease (AD), and Aβ oligomers are considered the most toxic species. Therefore, the detection and clearance of Aβ oligomers are crucial for the theranostic strategies for AD. However, effective methods for the detection of Aβ oligomers are rare, and only few of the oligomer-specific sensors have therapeutic functions as well. Recent studies have demonstrated that the toxicity of Aβ oligomers is related to the number of exposed hydrophobic residues. In this study, an oligomer-specific fluorescent probe, which was based on the hydrophobic regions that are exposed on Aβ oligomer surfaces was designed and synthesized. For improving the ability to recognize Aβ oligomers, the in situ treatment of AD symptoms and the ability to penetrate the blood-brain barrier, the probe and KLVFF peptide (an Aβ-target peptide) were modified on the surfaces of magnetic nanoparticles (MNP@NFP-pep). This complex could detect Aβ oligomers specifically, and achieve the wireless deep magnetothermally mediated disaggregation of Aβ aggregates with an alternating magnetic field. This work provides new insights into the development of a "sense and treat" system for AD therapy.

Recent clinical and epidemiological research has shown that insulin is associated with the pathological mechanisms of Alzheimer's disease (AD) and can protect against the oxidative stress triggered by amyloid-β peptide (Aβ). Herein, we present a systematic study on how the cross-fibrillation of insulin and Aβ is influenced by the surface chirality of an interface designed to mimic their aggregation on the cytomembrane. Intriguingly, the surface chirality strongly affected the aggregation kinetics, structure, morphology, and cellular responses of the cross-aggregates of insulin and Aβ. On a D-phenylalanine-modified surface, Aβ induced insulin to co-aggregate into β-sheet-rich fibrils and cross-fibrils that showed a pronounced cellular toxicity. However, on an L-phenylalanine-modified surface, insulin and Aβ formed non-toxic amorphous aggregates. Our work indicates that surface chirality can influence the cross-fibrillation of Aβ and insulin as well as the cytotoxicity of their aggregates.

Zinc oxide nanoparticles (ZnO NPs), as a new type of pH-sensitive drug carrier, have received much attention. ZnO NPs are stable at physiological pH, but can dissolve quickly in the acidic tumor environment (pH < 6) to generate cytotoxic zinc ions and reactive oxygen species (ROS). However, the protein corona usually causes the non-specific degradation of ZnO NPs, which has limited their application considerably. Herein, a new type of pH-sensitive nanoreactor (ZnO-DOX@F-mSiO₂-FA), aimed at reducing the non-specific degradation of ZnO NPs, is presented. In the acidic tumor environment (pH < 6), it can release cytotoxic zinc ions, ROS, and anticancer drugs to kill cancer cells effectively. In addition, the fluorescence emitted from fluorescein isothiocyanate (FITC)-labeled mesoporous silica (F-mSiO₂) and doxorubicin (DOX) can be used to monitor the release behavior of the anticancer drug. This report provides a new method to avoid the non-specific degradation of ZnO NPs, resulting in synergetic therapy by taking advantage of ZnO NPs-induced oxidative stress and targeted drug release.

Amyloid β-peptide (Aβ) aggregation is a critical step in the pathogenesis of Alzheimer's disease (AD). Inhibition of Aβ production, dissolution of existing aggregates and clearance of Aβ represent valid therapeutic strategies against AD. Herein, a novel platinum(Ⅱ)-coordinated graphitic carbon nitride (g-C₃N₄) nanosheet (g-C₃N₄@Pt) has been designed to covalently bind to Aβ and modulate the peptide's aggregation and toxicity. Furthermore, g-C₃N₄@Pt nanosheets possess high photocatalytic activity and can oxygenate Aβ upon visible light irradiation, remarkably attenuating both the aggregation potency and neurotoxicity of Aβ. Due to its ability to cross the blood-brain barrier (BBB) and its good biocompatibility, g-C₃N₄@Pt nanosheet is a promising inhibitor of Aβ aggregation. This study may serve as a model for the engineering of novel multifunctional nanomaterials used for the treatment of AD.

Proteolytic degradation of amyloid-β (Aβ) aggregates and clearance of Aβ-induced reactive oxygen species (ROS) have received significant attention for the treatment of Alzheimer's disease (AD). However, it is difficult, and often unfeasible, to directly upregulate or transport intracellular native enzymes. More importantly, penetration of the blood-brain barrier (BBB) has presented a major impediment. Herein, we report on the rational design of a polyoxometalatebased nanozyme with both protease-like activity for depleting Aβ aggregates, and superoxide dismutase (SOD)-like activity for scavenging Aβ-mediated ROS. Furthermore, this nanozyme acts as a metal chelator to remove Cu from Cu-induced Aβ oligomers. More intriguingly, the nanozyme can cross the BBB and exhibits low toxicity. This work provides new insights into the design and synthesis of inorganic nanozymes as multifunctional therapeutic agents in the treatment of AD.