An Activatable Nanoenzyme Reactor for Coenhanced Chemodynamic and Starving Therapy Against Tumor Hypoxia and Antioxidant Defense System

It is critical to improve the efficiency of cancer therapy with minimized side effects. Chemodynamic therapy (CDT) is a tumor therapeutic strategy designed to generate abundant reactive oxygen species (ROS) at tumor sites through a Fenton or Fenton-like reaction. Recently, this developing scheme has demonstrated an incredible promise for tumor therapy. The process involved could induce cell death without the input of external energy, and this could only occur via the conversion of hydrogen peroxide (H2O2) to hydroxyl radicals (center dot OH). Although Fenton or Fenton-like reactions are being exploited for CDT, along with an application of oxidation reactions to supplement H2O2, it has been proven that in cancer cells, the high levels of the existing antioxidants could suppress CDT via center dot OH depletion, and, unfortunately, tumor hypoxia also inhibits the oxidation reactions. Herein, the authors aimed to fabricate an activatable nanoenzyme reactor (NER) to solve this challenge. Fluorescent reporters (FRs) and bioenzyme glucose oxidase (GOX) were coassembled on nanozyme MnO2 nanosheets, which was enwrapped by the tumor-targeting material, hyaluronic acid (HA). NER was internalized explicitly by cancer cells through ligand/receptor recognition- mediated endocytosis, followed by intracellular hyaluronidase (HAase)-dependent activation. As a result, the oxygen level was improved, and the antioxidants were depleted, leading to the promotion of glucose consumption and an increase in center dot OH level. Thus, the NER exhibited multiple effects to induce coenhanced, chemodynamic and starving therapy against tumor hypoxia and antioxidant defense system to achieve a [GRAPHICS] favorable targeted tumor therapeutic, via these rigorously highly effective, and targeted biochemical reactions both in an in vitro cultured cancer cells systemor in an in vivo mice tumor model.

Automated summary

The article introduces a nanotechnology-based chemodynamic therapy (CDT) approach using a nanoenzyme reactor (NER) to increase oxygen levels, deplete antioxidants, and increase reactive oxygen species, in order to combat tumor hypoxia and antioxidant defense systems.