Artemisinin and its derivatives have emerged as promising therapeutic agents for cancer therapy by endogenous iron-mediated generation of free radicals. However, the enhanced antioxidant defense systems in cancer cells provide them with resistance to oxidative damage, greatly antagonizing the therapeutic efficacy that relies on inducing oxidative stress. Herein, a metal-organic framework (MOF)-based nanoplatform (CMD) is constructed to disrupt the cellular redox homeostasis and selectively potentiate the cytotoxicity of dihydroartemisinin for cancer therapy. In cancer cells, the copper(II) sites in the MOF nanocarrier of CMD can efficiently weaken the cellular antioxidant capacity by depleting the overexpressed glutathione, simultaneously leading to the decomposition of the framework structure and the release of the encapsulated dihydroartemisinin. As a result, the damaged antioxidant defense system of cancer cells reduces its effect on oxidative stress alleviation and strengthens the therapeutic efficacy of dihydroartemisinin. On contrast, the low concentration of cellular glutathione in normal cells protects them from dihydroartemisinin-induced cytotoxicity by decelerating the drug release. In vivo results demonstrate that CMD could completely suppress the tumor growth in mice and show no evidence of toxicity, providing an effective strategy for the practical usage of dihydroartemisinin in cancer therapy.

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.

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.

Accurate regulation of cellular zinc signaling is imperative to decipher underlying zinc functions and develop new therapeutic agents. However, the ability to modulate zinc in a spatiotemporal manner remains elusive. We herein report an intelligent spiropyran-upconversion (SP-UCNPs) based nanosystem that enables near-infrared (NIR) light-controlled zinc release at precise times and locations. The magnitude of zinc release can be simply manipulated by varying the duration of NIR irradiation. Moreover, the utilization of NIR light not only showed little damage to cells but also significantly improved penetration depth. By evaluating activity of a model protein, phosphatase 2A, we further validated zinc signaling activation. Importantly, our strategy may be broadly applicable to other types of metal ions, like the ubiquitous second messenger calcium. More importantly, our strategy can potentially enable the precise control of specific signaling pathways of metal ions while minimizing cellular damage, facilitating the advanced manipulation of cellular dynamics.

We report a new strategy for improving the efficiency of non-specific amyloidosis therapeutic drugs by coating amyloid-responsive lipid bilayers. The approach had drawn inspiration from amyloid oligomer-mediated cell membrane disruption in the pathogenesis of amyloidosis. A graphene-mesoporous silica hybrid (GMS)-supported lipid bilayer (GMS-Lip) system was used as a drug carrier. Drugs were well confined inside the nanocarrier until encountering amyloid oligomers, which could pierce the lipid bilayer coat and cause drug release. To ensure release efficiency, use of a near-infrared (NIR) laser was also introduced to facilitate drug release, taking advantage of the photothermal effect of GMS and thermal sensitivity of lipid bilayers. To facilitate tracking, fluorescent dyes were co-loaded with drugs within GMS-Lip and the NIR laser was used once the oligomer-triggered release had been signaled. Because of the spatially and temporally controllable property of light, the NIR-assisted release could be easily and selectively activated locally, by tracking the fluorescence signal. Our design is based on amyloidosis pathogenesis, the cytotoxic amyloid oligomer self-triggered release via cell membrane disruption, for the controlled release of drug molecules. The results may shed light on the development of pathogenesis-inspired drug delivery systems.