Biomimetic nanoflowers by self-assembly of nanozymes to induce intracellular oxidative damage against hypoxic tumors

TLDR

Reactive oxygen species–induced apoptosis is a promising strategy for malignant neoplasms, yet current systems rely on oxygen status or external stimuli, limiting efficacy in hypoxic tumors. The study develops a biomimetic nanoflower that self‑assembles nanozymes to catalyze intracellular reactions producing ROS under both normoxic and hypoxic conditions without external stimuli. PtCo nanoparticles direct MnO₂ growth, and by tuning reactant ratios, MnO₂@PtCo nanoflowers are formed where PtCo mimics oxidase and MnO₂ mimics catalase, yielding high catalytic efficiency. These nanoflowers relieve hypoxia, induce ROS‑mediated apoptosis, and achieve remarkable, specific tumor growth inhibition.

Abstract

Reactive oxygen species (ROS)-induced apoptosis is a promising treatment strategy for malignant neoplasms. However, current systems are highly dependent on oxygen status and/or external stimuli to generate ROS, which greatly limit their therapeutic efficacy particularly in hypoxic tumors. Herein, we develop a biomimetic nanoflower based on self-assembly of nanozymes that can catalyze a cascade of intracellular biochemical reactions to produce ROS in both normoxic and hypoxic conditions without any external stimuli. In our formulation, PtCo nanoparticles are firstly synthesized and used to direct the growth of MnO2. By adjusting the ratio of reactants, highly-ordered MnO2@PtCo nanoflowers with excellent catalytic efficiency are obtained, where PtCo behaves as oxidase mimic and MnO2 functions as catalase mimic. In this way, the well-defined MnO2@PtCo nanoflowers not only can relieve hypoxic condition but also induce cell apoptosis significantly through ROS-mediated mechanism, thereby resulting in remarkable and specific inhibition of tumor growth.