Combining H2O2-Supplying Iron Peroxide Nanoclusters with GSH-Depleting Gold Nanoclusters for Enhanced Chemodynamic Therapy via Amplification of Oxidative Stress

Cerium molybdate-doped polyaniline nanoplatform for GSH-depletion-enhanced chemodynamic/NIR-II photothermal synergistic therapy via ferroptosis and immune activation

Cerium molybdate-doped polyaniline nanoparticles are developed to enable a synergistic combination of photothermal therapy (PTT) and CDT, thereby triggering immunogenic cell death (ICD) and enhancing antitumor immunity and presenting a robust nanoplatform integrating chemodynamic and photothermal therapies for potent cancer immunotherapy.

H2O2-Responsive Nanocatalysts for Synergistic Hydroxyl and Chlorine Radical-Mediated Tumor Therapy.

Free radicals with reactive chemical properties can combat tumors without inducing drug resistance. Reactive oxygen species (ROS) have been widely applied in tumor therapy; however, the prevalent hypoxic conditions within tumors severely hinder the generation of ROS, leading to suboptimal antitumor efficacy. Herein, we designed an endogenous H2O2-triggered chlorine radical nanogenerator (Cl•) and hydroxyl radicals(•OH), which have better kinetic advantages and higher catalytic activity in catalyzing the H2O2 reaction. In vitro cytotoxicity tests revealed that the nano-urchins induced marked cancer cell death (up to ∼80% at the highest tested concentration) in a concentration-dependent manner, attributable to the chlorine radical-mediated oxidative stress. Moreover, the H2O2-specific activation strategy reduces toxic side effects on normal tissues, thereby enhancing the safety of tumor therapy. Finally, compared with conventional Cu2O nanocatalysts that solely generate •OH, our designed nano-urchins exhibit enhanced therapeutic efficacy, which is mainly attributed to the synergistic therapeutic effect. Therefore, our nano-urchins can serve as a novel nanocatalyst for tumor therapy.

Nanosystem-Mediated Phototherapy (PDT/PTT) - Chemodynamic Therapy for Synergistic Antitumor Therapy: Strategies and Advances

This review constructs a refined mechanistic framework to elaborate the complementary mechanisms of PDT and PTT toward CDT in terms of reaction kinetics modulation, endogenous substrate replenishment, and tumor antioxidant defense inhibition, and the key bottlenecks hindering clinical translation.

Electrostatically assembled gold nanocluster-enhanced porphyrinic metal-organic framework nanozymes for oxygen-boosted photodynamic therapy of hypoxic tumors.

Tumor hypoxia severely limits the therapeutic efficacy of photodynamic therapy (PDT), which relies on molecular oxygen to generate cytotoxic reactive oxygen species (ROS). Herein, an electrostatically assembled gold nanocluster-porphyrinic metal-organic framework nanozyme (AuNCs-pMOF) was developed as an oxygen-supplying platform for enhanced PDT of hypoxic tumors. By integrating catalase-mimetic gold nanoclusters (AuNCs) with a porphyrin-based metal-organic framework (pMOF), the resulting AuNCs-pMOF nanocomposite catalyzes the decomposition of endogenous H2O2 to provide local O2, thereby supporting 1O2/ROS generation under oxygen-limited conditions. In vitro studies demonstrated that AuNCs-pMOF maintained efficient ROS production and phototoxicity under hypoxia, whereas pristine pMOF showed reduced PDT efficacy. In vivo antitumor evaluation further confirmed that AuNCs-pMOF combined with light irradiation markedly inhibited tumor growth and induced pronounced tumor cell death, while showing favorable short-term tolerability under the tested experimental conditions. Overall, this work presents an electrostatically assembled oxygen-supplying nanozyme platform to mitigate oxygen shortage during PDT and enhance therapeutic efficacy against hypoxic solid tumors.

Origin of Fe ions in ROS production induced in magnetic hyperthermia anti-cancer nanotherapy: release from iron oxide nanoparticles or not?

Cascade-Enhanced Chemodynamic Therapy via a Mitochondria-Targeted PEI-Fc-Gox Nanogel with Dual Antihypoxia and ROS Amplification.

The glucose oxidase (GOx)-catalyzed oxidation of glucose generates an acidic microenvironment and supplies H2O2 as the essential substrate for intracellular Fenton reactions. However, the efficiency of this process is often constrained by the hypoxic conditions in tumor tissues. To address this limitation, we developed a mitochondria-targeted PFAGD nanogel, by covalently conjugating ferrocene (Fc) and GOx onto a polyethylenimine (PEI) backbone and encapsulating atovaquone (ATO), a mitochondrial respiration inhibitor. Surface modification with DNA-TPP enabled mitochondrial targeting. The incorporated ATO effectively alleviated intracellular hypoxia, thereby promoting the GOx/Fc-mediated cascaded Fenton reaction. This process drove substantial ROS (particularly ·OH) generation, thereby amplifying chemodynamic therapy. Multiple cellular assays confirmed that the three-step cascade reaction in the PFAGD nanogel enhanced the proliferation inhibition effect on cancer cells, especially under hypoxic conditions. This self-reinforcing nanoplatform mitigates tumor hypoxia and enables sustained, localized ROS generation, offering a promising strategy for catalytic anticancer therapy.