Targeting Tumor Microenvironment by Metal Peroxide Nanoparticles in Cancer Therapy

Abstract

Solid tumors have a unique tumor microenvironment (TME), which includes hypoxia, low acidity, and high hydrogen peroxide and glutathione (GSH) levels, among others. These unique factors, which offer favourable microenvironments and nourishment for tumor development and spread, also serve as a gateway for specific and successful cancer therapies. A good example is metal peroxide structures which have been synthesized and utilized to enhance oxygen supply and they have shown great promise in the alleviation of hypoxia. In a hypoxic environment, certain oxygen-dependent treatments such as photodynamic therapy and radiotherapy fail to respond and therefore modulating the hypoxic tumor microenvironment has been found to enhance the antitumor impact of certain drugs. Under acidic environments, the hydrogen peroxide produced by the reaction of metal peroxides with water not only induces oxidative stress but also produces additional oxygen. This is achieved since hydrogen peroxide acts as a reactive substrate for molecules such as catalyse enzymes, alleviating tumor hypoxia observed in the tumor microenvironment. Metal ions released in the process can also offer distinct bioactivity in their own right. Metal peroxides used in anticancer therapy are a rapidly evolving field, and there is good evidence that they are a good option for regulating the tumor microenvironment in cancer therapy. In this regard, the synthesis and mechanisms behind the successful application of metal peroxides to specifically target the tumor microenvironment are highlighted in this review. Various characteristics of TME such as angiogenesis, inflammation, hypoxia, acidity levels, and metal ion homeostasis are addressed in this regard, together with certain forms of synergistic combination treatments.

Addressing the gaps in homeostatic mechanisms of copper and copper dithiocarbamate complexes in cancer therapy: a shift from classical platinum-drug mechanisms

“…A recent review has discussed the various ways of targeting the tumor microenvironment to enhance the efficacy of other anticancer drugs. 84 Copper bis(thiosemicarbazone) complexes have also been attached to particular peptides for targeted delivery to boost specificity towards cancer cells while minimizing damage to normal cells. 17,[85][86][87] Copper has been shown in studies to increase the ability of malignant cells to spread by activating metabolic and proliferative enzymes.…”

Targeting Hypoxia-Inducible Factor-1 (HIF-1) in Cancer: Emerging Therapeutic Strategies and Pathway Regulation

“…The presence of hypoxic conditions leads to a reduction in the rate of cell proliferation in normal (non-cancerous) cells, imposing a constraint on the expansion of new oxygen-consuming cells. The hypoxic environment is a defining feature of the tumor microenvironment, wherein the excessive and uncontrolled cellular division and proliferation lead to disparities in oxygen usage and an inadequate oxygen supply that exceeds the capacity of the local vascular system [ 2 ]. Cancer cells can adapt to hypoxic conditions by modulating their metabolic pathways through changes in gene expression and enzyme activity [ 3 ].…”

Advances in Nanodelivery Systems Based on Metabolism Reprogramming Strategies for Enhanced Tumor Therapy

“…Consequently, this must be taken into account when treating tumors. Nanodelivery systems are well-used in metabolism reprogramming strategies due to their excellent drug loading, target modification, and ability to protect enzyme activity. − The metabolite of lactic acid, H 2 O 2 , could in turn react with many metal ions, such as Fe 2+ , Cu 2+ , and Zn 2+ , to generate oxidative hydroxyl radicals for tumor treatment. , These metal ion compounds could be easily processed to obtain many types of nanodelivery systems. , This built a bridge between nanodelivery systems and metabolism reprogramming strategies. Unexpectedly, tumors improve their resistance to oxidative stress by enhancing their own lipid metabolism , and amino acid metabolism, e.g., glutamine metabolism, glutathione (GSH) metabolism, etc. , These issues in turn need to be addressed by nanodelivery systems based on tumor metabolism reprogramming strategies.…”