Nanozyme-based Clusterphene for Enhanced Electrically Catalytic Cancer Therapy.

Nanozyme mediated catalytic therapy is an attractive strategy for cancer therapy. However, the nanozymes are tended to assemble into 3D architectures, resulting in poor catalytic efficiency for therapy. This study designs the assembly of nanozymes and natural enzymes into the layered structures featuring hexagonal pores as nanozyme clusterphene and investigates their catalytic therapy with the assistance of electric field. The nanozyme-based clusterphene consists of polyoxometalate (POM) and natural glucose oxidase (GOx), named POMG-based clusterphene, which facilitate multi-enzyme activities including peroxidase (POD), catalase (CAT), and glutathione oxidase (GPx). The highly ordered layers with hexagonal pores of POMG units significantly improve the peroxidase-like (POD-like) activity of the nanozyme and thus the sustained production of reactive oxygen species (ROS). At the same time, GOx can increase endogenous H2O2 and produce gluconic acid while consuming glucose, the nutrient of tumor cell growth. The results indicate that the POD-like activity of POMG-based clusterphene increase approximately sevenfold under electrical stimulation compared with Nd-substituted keggin type POM cluster (NdPW11). The experiments both in vitro and in vivo show that the proposed POMG-based clusterphene mediated cascade catalytic therapy is capable of efficient tumor inhibiting and preventing tumor proliferation in tumor-bearing mice model, promising as an excellent candidate for catalytic therapy.

Strategies to Reverse Hypoxic Tumor Microenvironment for Enhanced Sonodynamic Therapy.

Sonodynamic therapy (SDT) has emerged as a highly effective modality for the treatment of malignant tumors owing to its powerful penetration ability, noninvasiveness, site-confined irradiation, and excellent therapeutic efficacy. However, the traditional SDT, which relies on oxygen availability, often fails to generate a satisfactory level of reactive oxygen species because of the widespread issue of hypoxia in the tumor microenvironment of solid tumors. To address this challenge, various approaches are developed to alleviate hypoxia and improve the efficiency of SDT. These strategies aim to either increase oxygen supply or prevent hypoxia exacerbation, thereby enhancing the effectiveness of SDT. In view of this, the current review provides an overview of these strategies and their underlying principles, focusing on the circulation of oxygen from consumption to external supply. The detailed research examples conducted using these strategies in combination with SDT are also discussed. Additionally, this review highlights the future prospects and challenges of the hypoxia-alleviated SDT, along with the key considerations for future clinical applications. These considerations include the development of efficient oxygen delivery systems, the accurate methods for hypoxia detection, and the exploration of combination therapies to optimize SDT outcomes.

Polyoxometalate-Nanozyme-Integrated Nanomotors (POMotors) for Self-Propulsion-Promoted Synergistic Photothermal-Catalytic Tumor Therapy.

Enzyme-powered nanomotors have demonstrated promising potential in biomedical applications, especially for catalytic tumor therapy, owing to their ability of self-propulsion and bio-catalysis. However, the fragility of natural enzymes limits their environmental adaptability and also therapeutic efficacy in catalysis-enabled tumor therapy. Herein, polyoxometalate-nanozyme-based light-driven nanomotors were designed and synthesized for targeted synergistic photothermal-catalytic tumor therapy. In this construct, the peroxidase-like activity of the P2 W18 Fe4 polyoxometalates-based nanomotors can provide self-propulsion and facilitate their production of reactive oxygen species thus killing tumor cells, even in the weakly acidic tumor microenvironment. Conjugated polydopamine endows the nanomotors with the capability of light-driven self-propulsion behavior. After 10 min of NIR (808 nm) irradiation, along with the help of epidermal growth factor receptor antibody, the targeted accumulation and penetration of nanomotors in the tumor enabled highly efficient synergistic photothermal-catalytic therapy. This approach overcomes the disadvantages of the intrinsically fragile nature of enzyme-powered nanomotors in physiological environments and, more importantly, provides a motility-behavior promoted synergistic anti-tumor strategy.

Recent Advances in Polyoxometalate Based Nanoplatforms Mediated Reactive Oxygen Species Cancer Therapy.

The potential of reactive oxygen species (ROS) cancer therapy in tumor treatment has been greatly enhanced by the introduction of catalytically superior polyoxometalate (POM)-based nanoplatforms, mainly composed of atomic clusters consisting of pre-transition metals and oxygen. These nanoplatforms have unique advantages, such as Fenton activity at neutral pH, induction of cellular ferroptosis instead of just apoptosis, and sensitivity to external field stimulation. However, there are also inevitable challenges such as neutralization of ROS by the antioxidant system of the tumor microenvironment (TME), hypoxia, and limited hydrogen peroxide concentrations. This review article aims to provide an overview of recent research advancements in POM-based nanoplatforms for ROS therapy from the perspective of chemical reactions and biological processes, addressing endogenous and exogenous factors that affect the antitumor efficacy. Endogenous factors include the mechanism of ROS generation by POM, the impact of pH and antioxidant systems on POM, and the various manners of tumor cell death. Exogenous stimuli mainly include light, heat, X-rays, and electricity. The article analyzes the specific mechanisms of action of each influencing factor in the first two sections, concluding with the limitations of the present study and some possible directions for future research.

Polyoxometalate Modified by Zeolite Imidazole Framework for the pH-Responsive Electrodynamic/Chemodynamic Therapy.

Electrodynamic therapy (EDT) and chemodynamic therapy (CDT) have the potential for future tumor treatment; however, their underlying applications are greatly hindered owing to their inherent drawbacks. The combination of EDT and CDT has been considered to be an effective way to maximize the superiorities of these two ROS-based methodologies. However, the development of novel nanomaterials with "one-for-all" functions still remains a big challenge. In this work, the polyoxometalate nanoparticles (NPs) were decorated using the zeolite imidazole framework (POM@ZIF-8) in order to integrate the EDT with CDT. The resulting POM@ZIF-8 NPs can effectively induce the generation of reactive oxygen species (ROS) via a catalytic reaction on the surface of POM NPs induced by an electric field (E). At the same time, POM@ZIF-8 NPs can catalyze the intracellular H2O2 into ROS via a Fenton-like reaction, thereby achieving the combination of EDT and CDT. Besides, since ZIF-8 is acid-responsive, it can protect normal tissues and avoid side effects. Of great note is that the cytotoxicity and the apoptosis rate of the POM@ZIF-8+E group (80%) were found to be significantly higher than that of the E group (55%). As a result, a high tumor inhibition phenomenon can be observed both in vitro and in vivo. The present study thus provides an alternative concept for combinational therapeutic modality with exceptional efficacy.