Journal Article

Hollow MnO 2 Nanozyme with NO Prodrug to Boost Synergistic CDT/PDT/Gas Therapy via Oxidative Stress Cascade

Hu, Junjian, Yin, Ting, Qiu, Long, Ma, Zhilong, Bai, Jinyu, Cui, Daxiang, Fang, Lijing, Wu, Yusen, Sun, Jianbo, Liu, Xuyi

2026

Overview

Photodynamic therapy (PDT) utilizes photosensitizers to generate reactive oxygen species (ROS) to kill tumors. However, the tumor's hypoxia and the limitations of a single ROS mechanism severely restrict its efficacy. This study aims to develop a synergistic nano-catalytic system (HMO) based on hollow manganese dioxide (HMnO ) loaded with a novel nitric oxide (NO) donor (Methylene Blue - NO, MB-NO), which overcomes these obstacles through multiple synergistic effects. Preliminary experiments confirmed the synthesis of HMO. Systematic studies were conducted on the chemodynamic therapy (CDT)/PDT/NO properties of HMO as well as its anti-tumor activity in vivo and in vitro. Finally, the in vivo safety of HMO was evaluated. Preparation by the HMO is 189 nm nano particle size, Zeta potential for -37 ± 1.4 mV, exhibit excellent stability. In vitro experiments showed that the cellular uptake of HMO was time-dependent. In terms of cytotoxicity, the cell survival rate of the HMO group was 65.9%, significantly lower than that of the free HMnO (89.1%) and MB-NO (85.1%); after 5 min of 660 nm laser irradiation, the cell survival rate of the HMO group further dropped to 48.5%. In the animal experiments of tumor xenograft models, the tumor inhibition rate of the HMO combined with 660 nm laser irradiation for 5 min group was as high as 81.3%, and it did not cause acute inflammation in the main organs, demonstrating good biological safety. In summary, the HMO nanoparticles exhibit excellent anti-tumor effects. This strategy combines CDT/PDT/gas therapy, enabling the synergistic cascade of NO/ROS/reactive nitrogen oxide species (RNOS) to promote tumor cell apoptosis and inhibit tumor growth, thereby achieving a cascading amplification of therapeutic effects and providing a treatment solution to overcome the inherent limitations of traditional photodynamic therapy.

• Subject: Animals / Cell Line, Tumor / Cell Survival - drug effects / Female / Humans / Manganese Compounds - chemistry / Manganese Compounds - pharmacology / Methylene Blue - chemistry / Methylene Blue - pharmacology / Mice / Mice, Inbred BALB C / Nanoparticles - chemistry / Nitric Oxide - chemistry / Nitric Oxide - pharmacology / Nitric Oxide Donors - chemistry / Nitric Oxide Donors - pharmacology / Oxidative Stress - drug effects / Oxides - chemistry / Oxides - pharmacology / Photochemotherapy - methods / Photosensitizing Agents - chemistry / Photosensitizing Agents - pharmacology / Prodrugs - chemistry / Prodrugs - pharmacology / Reactive Oxygen Species - metabolism