Catalytic MnWO₄ Nanorods for Chemodynamic Therapy Synergized Radiotherapy of Triple Negative Breast Cancer

Abstract

Nanomedicine‐based synergy of chemodynamic therapy (CDT) and radiotherapy (RT) modulated by tumor microenvironment enables rapid tumor ablation, which holds great hope for the refractory and recurrent cancers, such as triple negative breast cancer (TNBC). The clinical translation of hafnium oxide (HfO2), commercially named as NBTXR3, has aroused new research focus on single‐component inorganic nanomedicines as clinical candidates. Herein, the single‐component MnWO4 is first reported as a new kind of Fenton‐like agent yet radiosensitizer for TNBC treatment undergoing the synergistic CDT/RT mechanism. MnWO4 nanorods are synthesized via a simple one‐pot hydrothermal method and then undergo a layer‐by‐layer PEGylation to obtain bioavailable MnWO4‐PEG (MWP). MWP‐based Fenton‐like reaction efficacy depends on reaction time, temperatures, pH values, and MWP concentrations. Mn‐triggered chemodynamic effect delays RT‐induced DNA damage repair and sorts cell cycles distribution toward radiosensitive phases, while W‐mediated radiosensitization improves the tumoral H2O2 overexpression to enhance CDT, remarkably amplifying of the intracellular oxidative stress to boost 4T1 cell apoptosis. In vitro and in vivo evaluations further demonstrate the effectiveness and biosafety of MWP‐based synergistic therapy. Considering the potential magnetic resonance and computed tomography imaging capabilities, MWP can be expected as an intelligent cancer theranostics for imaging‐guided cancer therapy in clinic in the future.

Nanointegrative In Situ Reprogramming of Tumor-Intrinsic Lipid Droplet Biogenesis for Low-Dose Radiation-Activated Ferroptosis Immunotherapy

“…Notably, treating H-4T1 cells with TCPP@Hf-TK-PEG-PAMAM-FA@siHIF-1α+IR also induced obvious activation of the cell apoptosis cascade, which was consistent with the cell death mechanism under IR exposure (Figures I and S6D–E). − These data collectively supported that TCPP@Hf-TK-PEG-PAMAM-FA@siHIF-1α could substantially promote the direct cytotoxicity of LDR by triggering tumor cell ferroptosis and amplifying post-IR DNA damage (Figure H). On account of its potent radiosensitization effect, we detected that the combination treatment of TCPP@Hf-TK-PEG-PAMAM-FA@siHIF-1α and low-dose IR could strongly inhibit the growth of H-4T1 cells in vitro, of which the cell viability was below 39.89% after incubating with 50 μg/mL TCPP@Hf-TK-PEG-PAMAM-FA@siHIF-1α and 4Gy IR for 24 h (Figure S10A–B).…”

Multivalence Manganese Mediated Dual ROS Generator for Augmented Chemodynamic Therapy and Activated Antitumor Immunogenic Responses

“…More recently, multimodal synergistic therapeutic strategies toward increasing the types of ROS, including photodynamic therapy (PDT) or sonodynamic therapy (SDT) combined with CDT, have exhibited enhanced therapeutic efficacy and ICD. − However, development of a nanoplatform that generates different types of ROS in one agent is rare. Manganese (Mn) ions with multiple valences have been confirmed to generate ·OH by a Fenton-like reaction in H 2 O 2 overproduced condition and singlet oxygen ( 1 O 2 ) in an acidic environment. − Therefore, Mn based nanomaterials are promising candidates to achieve CDT with dual types of synchronous ROS generation, which improves the efficacy of CDT and enhances the ICD effect.…”

NIR-II-Responsive Versatile Nanozyme Based on H2O2 Cycling and Disrupting Cellular Redox Homeostasis for Enhanced Synergistic Cancer Therapy

“…Conversely, an overproduction of ROS is associated with cellular pathological states including cancer, neurodegenerative diseases, and inflammation. − Elevated ROS levels could induce cellular oxidative stress, leading to lipids, proteins, and DNA damage, culminating in cell apoptosis. As a result, numerous approaches based on leveraging excessive ROS at pathological sites have been developed for cancer therapy, such as photodynamic therapy, sonodynamic therapy, , radiation therapy, chemodynamic therapy, and synergistic therapy. , However, the limited concentration of H 2 O 2 , the overexpression of glutathione (GSH) and hypoxic environment in cancer cells, the relatively low tissue-penetrating depth of the laser, and the relatively low activity of the probe still hampered the treatment effect. Therefore, there is an urgent need to design a strategy that could disturb the redox homeostasis and overcome the tumor microenvironment to enhance ROS generation for improved cancer therapy.…”