Fenton/Fenton-like metal-based nanomaterials combine with oxidase for synergistic tumor therapy

Abstract

Chemodynamic therapy (CDT) catalyzed by transition metal and starvation therapy catalyzed by intracellular metabolite oxidases are both classic tumor treatments based on nanocatalysts. CDT monotherapy has limitations including low catalytic efficiency of metal ions and insufficient endogenous hydrogen peroxide (H2O2). Also, single starvation therapy shows limited ability on resisting tumors. The “metal-oxidase” cascade catalytic system is to introduce intracellular metabolite oxidases into the metal-based nanoplatform, which perfectly solves the shortcomings of the above-mentioned monotherapiesIn this system, oxidases can not only consume tumor nutrients to produce a “starvation effect”, but also provide CDT with sufficient H2O2 and a suitable acidic environment, which further promote synergy between CDT and starvation therapy, leading to enhanced antitumor effects. More importantly, the “metal-oxidase” system can be combined with other antitumor therapies (such as photothermal therapy, hypoxia-activated drug therapy, chemotherapy, and immunotherapy) to maximize their antitumor effects. In addition, both metal-based nanoparticles and oxidases can activate tumor immunity through multiple pathways, so the combination of the “metal-oxidase” system with immunotherapy has a powerful synergistic effect. This article firstly introduced the metals which induce CDT and the oxidases which induce starvation therapy and then described the “metal-oxidase” cascade catalytic system in detail. Moreover, we highlight the application of the “metal-oxidase” system in combination with numerous antitumor therapies, especially in combination with immunotherapy, expecting to provide new ideas for tumor treatment.

A tumor microenvironment-responsive poly(amidoamine) dendrimer nanoplatform for hypoxia-responsive chemo/chemodynamic therapy

“…Among various drugs, hypoxia-activated prodrugs are of particular interest [ 28 ], because they can be converted to potent anticancer drugs through specific reductase in hypoxic cells [ 25 , 29 ] and effectively kill hypoxic tumor cells within malignant solid tumors [ 27 , 30 ]. It is reasonable to speculate that the combination of hypoxia-sensitive chemotherapy and CDT may enhance the antitumor efficacy to hypoxia tumors and result in the cooperative enhancement in tumor inhibition [ 31 , 32 ]. As the lead compound in benzotriazine-di-N-oxide class of hypoxic cytotoxins, tirapazamine (TPZ) may undergo two different types of breakage reactions in hypoxic tumor cells to produce ·OH and benzotriazinyl (BTZ) radical, inducing DNA strand breakage and topoisomerase II poisoning (Additional file 1 : Fig.…”

Norcantharidin Nanostructured Lipid Carrier (NCTD-NLC) Suppresses the Viability of Human Hepatocellular Carcinoma HepG2 Cells and Accelerates the Apoptosis

“…Tumor tissue has abnormal vasculature (excessive vascularization) with large gaps in poorly aligned and defective endothelial cells, so that nanodrug delivery systems can passively aggregate tumor tissue, which is referred to as the tumor “EPR effect” (enhanced penetration and retention effect) [ 27 ]. The tumor “EPR effect” of nanodrug delivery systems is closely related to the composition, size, surface charge, and administration route of nanodrug delivery systems [ 28 ]. It was found that due to the rapid growth of tumors, discontinuous capillaries, and small interstitial windows, nanoparticles can easily overflow from blood vessels and reach the tumor stroma, so that they can accumulate in the tumor site and can also be carried out in the extracellular space.…”

Mitochondria-Targeting Chemodynamic Therapy Nanodrugs for Cancer Treatment

“…The slower reaction rate of CDT based on Fenton reaction is also a major factor limitation of the effectiveness of CDT ( Cao et al, 2021 ). The high temperature from hyperthermia therapy (HT) can improve the rate of the Fenton/Fenton-like reaction to greatly increase the efficacy of CDT ( Liu et al, 2019 ; Danewalia and Singh, 2021 ).…”