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

Abstract

Gastric cancer (GC) is a serious disease with high morbidity and mortality rates worldwide. Chemotherapy plays a key role in GC treatment, while inevitable drug resistance and systematic side effects hinder its clinical application. Fenton chemistry-based chemodynamic therapy (CDT) has been used as a strategy for cancer ferroptosis, and the CDT efficiency could be enhanced by photothermal therapy (PTT). With the trend of treatment and diagnosis integration, the combination of magnetic resonance imaging (MRI) and CDT/PTT exhibits enormous progress. Herein, we constructed a platform based on PEGylated manganese-containing polydopamine (PDA) nanoparticles, named as PEG-PDA@Mn (PP@Mn) NPs. The PP@Mn NPs were stable and globular. Furthermore, they demonstrated near-infrared (NIR)-triggered PTT and Fenton-like reaction-based CDT effects and T1-weighted MRI capabilities. According to in vitro studies, the PP@Mn NPs trigger ferroptosis in cancer cells by producing abundant reactive oxygen species (ROS) via a Fenton-like reaction combined with PTT. Furthermore, in vivo studies showed that, under MRI guidance, the PP@Mn NPs combined with the PTT at the tumor region, have CDT anti-tumor effect. In conclusion, the PP@Mn NPs could provide an effective strategy for CDT/PTT synergistic ferroptosis therapy for GC.

Targeted Magnetic Resonance Imaging/Near‐Infrared Dual‐Modal Imaging and Ferroptosis/Starvation Therapy of Gastric Cancer with Peritoneal Metastasis

“…However, their longitudinal relaxivity (r1) is relatively low (<9.0 m m −1 s −1 ), [ 14 ] and the sensitivity of MRI frequently depends on the high relaxivity values of contrast agents. [ 15 ] Wu et al constructed a dotted core‐shell type FeGd‐HN nanoparticle with super high r1 value (21.0 ± 1.3 m m −1 s −1 , B 0 = 7.0 T) and very low r2/r1 ratio for high contrast T 1 ‐weighted MRI of subcutaneous xenografts tumors, [ 16 ] but the accurate identification of small PM nodules continues to be a challenge. Previous studies have shown that compared with passive target delivery, decoration with active targeting ligands (including cRGD, RGD, or RGD2), which can actively identify specific receptors on the target cell, is efficient.…”

pH-Activated Ce-Doped Molybdenum Oxide Nanoclusters for Tumor Microenvironment Responsive Photothermal and Chemodynamic Therapy

“…Although Ce-based nanocomposites show good GSH consumption and radical generation for chemodynamic therapy, they still need other treatment (e.g., photothermal therapy) methods to enhance the therapeutic effect. Associated with the PTT capability, PTT/CDT combined therapy can be realized because the PTT reagent not only kills cancer cells by elevating the temperature but also accelerates the production of ROS in CDT . Therefore, endowing Ce with photothermal agents is beneficial to enhance their CDT efficacy …”

“…PTT capability, PTT/CDT combined therapy can be realized because the PTT reagent not only kills cancer cells by elevating the temperature but also accelerates the production of ROS in CDT. 15 Therefore, endowing Ce with photothermal agents is beneficial to enhance their CDT efficacy. 16 Photothermal therapy (PTT) is a hot topic in recent years in the field of biomedical and materials science study.…”

Single-cell transcriptomics uncover the key ferroptosis regulators contribute to cancer progression in head and neck squamous cell carcinoma

“…Ferroptosis is a newly discovered form of programmed cell death characterized by iron-dependent lethal accumulation of lipid peroxides (lipid reactive oxygen species or lipid ROS) that was recently identified as one of the mechanisms of cancer cell death in several cancers, including liver cancer, kidney cancer, bone cancer, and lung cancer ( Chen et al, 2022 ; Peng et al, 2023 ). Ferroptosis occurs when the levels of lipid ROS exceed the cellular antioxidative threshold and oxidative stress overload is induced in cells ( Zhang et al, 2022 ).…”