MnO₂-Based Nanomotors with Active Fenton-like Mn²⁺ Delivery for Enhanced Chemodynamic Therapy

Abstract

Chemodynamic therapy (CDT) is an emerging strategy for cancer treatment based on Fenton chemistry, which can convert endogenous H2O2 into toxic ·OH. However, the limited endocytosis of passive CDT nanoagents with low penetrating capability resulted in unsatisfactory anticancer efficacy. Herein, we propose the successful fabrication of a self-propelled biodegradable nanomotor system based on hollow MnO2 nanoparticles with catalytic activity for active Fenton-like Mn2+ delivery and enhanced CDT. Compared with the passive counterparts, the significantly improved penetration of nanomotors with enhanced diffusion is demonstrated in both the 2D cell culture system and 3D tumor multicellular spheroids. After the intracellular uptake of nanomotors, toxic Fenton-like Mn2+ is massively produced by consuming overexpressed intracellular glutathione (GSH), which has a strong scavenging effect on ·OH, thereby leading to enhanced cancer CDT. The as-developed MnO2-based nanomotor system with enhanced penetration and endogenous GSH scavenging capability shows much promise as a potential platform for cancer treatment in the near future.

Manganese-containing polydopamine nanoparticles as theranostic agents for magnetic resonance imaging and photothermal/chemodynamic combined ferroptosis therapy treating gastric cancer

“…As the concentration of the PP@Mn NPs increased, the MB absorption decreased, suggesting that the PP@Mn NPs produced abundant •OH ( Figure 1(J) ). The result was in accordance with previous report (Ou et al., 2021 ). Furthermore, to explore the influence of the photothermal effect on the Fenton-like reaction of the PP@Mn NPs, we placed the reaction systems in a water bath at 42 °C.…”

“…For the absorption time of 8 h, the PP@Mn NPs occupied approximately the entire cytoplasmic space. The fluorescence intensity of cellular Rho was quantified ( Figure 2(B) ), showing that the cellular uptake of the PP@Mn NPs increased within 8 h. The Mn 2+ in tumor cells can catalyze H 2 O 2 to •OH through the Fenton-like reaction (Liu et al., 2020 ; Ou et al., 2021 ). Moreover, tumor PTT can elevate the •OH level while improving the efficiency of the Fenton-like reactions (Liu et al., 2020 ; Zhou et al., 2021 ).…”

Redox dyshomeostasis strategy for tumor therapy based on nanomaterials chemistry

“…Mn 2+ could not only consume GSH but also display Fenton-like properties. 64–66 Based on this, Xiaoyuan Chen et al constructed MnO 2 -based mesoporous silica nanoparticles (MS@MnO 2 NP). 67 Once taken up by cancer cells, the MnO 2 shell was used to oxidize GSH to accumulate H 2 O 2 , which led to RDH, ultimately enhancing Mn 2+ -mediated CDT.…”

PDGFB targeting biodegradable FePt alloy assembly for MRI guided starvation-enhancing chemodynamic therapy of cancer

“…Recently, heavy metal ions including iron [ 11 ], copper [ 12 ], and manganese [ 13 ], have been utilized to catalyze the conversion of endogenous hydrogen peroxide (H 2 O 2 ) to highly toxic hydroxyl radicals (·OH), whose accumulation then triggers reactive oxygen species (ROS)-mediated oxidative stress and non-programmed cell apoptosis; this process is termed chemodynamic therapy (CDT) [ 14 – 17 ]. Recently, Tao’s group reported that surface-oxidized arsenene nanosheets with oxygen vacancies also catalyzed a Fenton-like reaction, and then generate ·OH and O 2 from H 2 O 2 [ 18 ], which provided a completely new concept for developing highly efficient CDT agent.…”