Doping Engineering to Modulate Lattice and Electronic Structure for Enhanced Piezocatalytic Therapy and Ferroptosis

Abstract

Piezocatalytic therapy, which generates reactive oxygen species (ROS) under mechanical force, has garnered extensive attention for its use in cancer therapy owing to its deep tissue penetration depth and less O2‐dependence. However, the piezocatalytic therapeutic efficiency is limited owing to the poor piezoresponse, low separation of electron‐hole pairs, and complicated tumor microenvironment (TME). Herein, a biodegradable, porous Mn‐doped ZnO nanocluster with enhanced piezoelectric effect is constructed via doping engineering. Mn‐doping not only induces lattice distortion to increase polarization but also creates rich oxygen vacancy (OV) for suppressing the recombination of electron‐hole pairs, leading to high‐efficiency generation of ROS under ultrasound (US) irradiation. Moreover, Mn‐doped ZnO shows TME‐responsive multienzyme‐mimic activity to generate ·OH and ·O2‒, as well as glutathione (GSH) depletion ability owing to the mixed valence of Mn (II/III), further aggravating oxidative stress in tumor cells. Density functional theory calculations show that Mn‐doping can improve the piezocatalytic performance because of the enhancement of polarization and enzyme activity of Mn‐ZnO due to the presence of OV. Beneficiating from the US‐triggered boosting of ROS generation and GSH depletion ability, Mn‐ZnO can significantly accelerate the accumulation of lipid peroxide and inactivate glutathione peroxidase 4 (GPX4) to induce ferroptosis. Our work may provide new guidance for exploring novel piezoelectric sonosensitizers for tumor therapy.This article is protected by copyright. All rights reserved

A metal–organic framework-integrated composite for piezocatalysis-assisted tumour therapy: design, related mechanisms, and recent advances

“…6a). 67 The introduction of Mn 2+ can induce distortion within the ZnO lattice, giving rise to an internal electric field and enhancing piezoelectricity. In addition, the incorporated Mn 2+ exhibited remarkable TME responsiveness and peroxidase (POD) and oxidase (OXD) activities, and thus can further produce ROS within tumour tissues.…”

Copper-based inorganic nanozymes enhance the electrical conductivity of tumors to synergistically induce the pyroptosis, ferroptosis, and apoptosis of tumors

“…24,25 CDT has been extensively studied for tumor therapy, with its anticancer activity primarily relying on the efficiency of Fenton or Fenton-like reactions. [26][27][28][29][30] Therefore, the activity of Fenton reaction catalysts, referred to as POD-like nanozymes, is a crucial factor in enhancing CDT efficiency. Classical Fenton catalysts, such as Fe species (ultrasmall iron oxide), have limited catalytic activity in the tumor microenvironment (TME) due to weak TME responses and low catalytic activity.…”

Activatable Plasmonic Versatile Nanoplatform for Glutathione-Depletion Augmented Ferroptosis and NIR-II Photothermal Synergistic Therapy

“…8% ID g −1 nanoplatform enriched in tumor tissue due to the enhanced permeability and retention (EPR) effect. 6 The highest concentration of AuSi@FePB was identified at the one-day postinjection and then gradually decreased. Therefore, the 24 h postinjection may be an optimum laser irradiation time-point after intravenous administration of AuSi@FePB to tumorbearing mice.…”

“…Meanwhile, there is ca. 8% ID g –1 nanoplatform enriched in tumor tissue due to the enhanced permeability and retention (EPR) effect . The highest concentration of AuSi@FePB was identified at the one-day postinjection and then gradually decreased.…”