Ternary Alloy PtWMn as a Mn Nanoreservoir for High‐Field MRI Monitoring and Highly Selective Ferroptosis Therapy

Abstract

Ferroptosis exhibits potential to damage drugresistant cancer cells. However, it is still restricted with the "off-target" toxicity from the undesirable leakage of metal ions from ferroptosis agents, and the lack of reliable imaging for monitoring the ferroptosis process in living systems. Herein, we develop a novel ternary alloy PtWMn nanocube as a Mn reservoir, and further design a microenvironment-triggered nanoplatform that can accurately release Mn ions within the tumor to increase reactive oxygen species (ROS) generation, produce O 2 and consume excess glutathione for synergistically enhancing nonferrous ferroptosis. Moreover, this nanoplatform exerts a responsive signal in high-field magnetic resonance imaging (MRI), which enables the real-time report of Mn release and the monitoring of ferroptosis initiation through the signal changes of T 1 -/ T 2 -MRI. Thus, our nanoplatform provides a novel strategy to store, deliver and precisely release Mn ions for MRI-guided high-specificity ferroptosis therapy.

Recent advances in sonodynamic therapy strategies for pancreatic cancer

“…As a result, SDT compensates for the penetration depth limitations encountered by other treatment methods, making it a promising approach for targeting tumors located in hard‐to‐reach areas; thus, it is particularly valuable for managing pancreatic cancer (He et al, 2023). Third, with the help of US, the efficiency of ROS generation is much higher than the therapy strategy based on catalytic medicine (Guan et al, 2022; Lu et al, 2020; Shi et al, 2021; Teng et al, 2021; Yang et al, 2022; Yue et al, 2022). Therefore, there is growing interest among researchers in exploring the potential of SDT for the treatment of pancreatic cancer.…”

Highly Penetrable Drug-Loaded Nanomotors for Photothermal-Enhanced Ferroptosis Treatment of Tumor

“…The accumulation of iron ions in cells may lead to cell death, which is characterized by iron-dependent lipid peroxidation. This is a kind of programmed cell death induced by the production of iron-dependent reactive oxygen species (ROS), which is defined as ferroptosis and has attracted extensive attention. − The mechanism of ferroptosis is closely related to the inactivation of glutathione peroxidase 4 (GPX4) and the production and accumulation of ROS by the Fenton/Fenton-like reaction, which ultimately leads to the accumulation of lipid peroxide (LPO). , Recently, many studies have involved the use of the Fenton/Fenton-like reaction to combine Fe-, Co-, Mn-, and Cu-based inorganic nanocatalysts with hydrogen peroxide (H 2 O 2 ) overexpressed in a tumor microenvironment (TME) to produce cytotoxic •OH, thus effectively inducing ferroptosis to treat tumor. , It can also inhibit the activity of GPX4 (the only enzyme in cell that can be used for the reduction of liposome peroxide) by consuming intracellular glutathione (GSH), so as to induce ferroptosis for tumor treatment. , …”

“…5,6 Recently, many studies have involved the use of the Fenton/Fenton-like reaction to combine Fe-, Co-, Mn-, and Cu-based inorganic nanocatalysts with hydrogen peroxide (H 2 O 2 ) overexpressed in a tumor microenvironment (TME) to produce cytotoxic •OH, thus effectively inducing ferroptosis to treat tumor. 7,8 It can also inhibit the activity of GPX4 (the only enzyme in cell that can be used for the reduction of liposome peroxide) by consuming intracellular glutathione (GSH), so as to induce ferroptosis for tumor treatment. 9,10 Although the new nanotherapy based on the ferroptosis mechanism has made great progress in tumor treatment research, there are still some problems that need to be solved urgently.…”

Hydrogen-Bonded Organic Frameworks Chelated Manganese for Precise Magnetic Resonance Imaging Diagnosis of Cancers

“…19,40 The magnetic hysteresis (M-H) loop of PFC-73-Mn exhibited typical paramagnetic behavior (Figure 2c). 41 The MRI relaxation in vitro was investigated in a 3.0 T MRI system, and the Mn element content was determined via atomic absorption spectroscopy (AAS) (Figure S8). The longitudinal relaxation rate (1/T 1 ) and transverse relaxation rate (1/T 2 ) revealed linear relationships with the concentrations of the Mn ions.…”

“…The magnetic hysteresis (M-H) loop of PFC-73-Mn exhibited typical paramagnetic behavior (Figure c) . The MRI relaxation in vitro was investigated in a 3.0 T MRI system, and the Mn element content was determined via atomic absorption spectroscopy (AAS) (Figure S8).…”