An AND Logic Gate for Magnetic‐Resonance‐Imaging‐Guided Ferroptosis Therapy of Tumors

Abstract

To improve the magnetic resonance imaging (MRI) efficiency and ferroptosis therapy efficacy of exceedingly small magnetic iron oxide nanoparticles (IO, < 5 nm) for tumors via enhancing the sensitivity of tumor microenvironment (TME) responsiveness, inspired by molecular logic gates, we designed and constructed a self‐assembled IO with a AND logic gate function. Typically, cystamine (CA) was conjugated onto the end of poly(2‐methylthio‐ethanol methacrylate) (PMEMA) to generate PMEMA‐CA. The PMEMA‐CA was grafted onto the surface of brequinar (BQR)‐loaded IO to form IO‐BQR@PMEMA. The self‐assembled IO‐BQR@PMEMA (SA‐IO‐BQR@PMEMA) was obtained due to the hydrophobicity of PMEMA. The carbon‐sulfur single bond of PMEMA‐CA can be oxidized by the reactive oxygen species (ROS) in TME to thio‐oxygen double bond, resulting in the conversion from being hydrophobic to hydrophilic. The disulfide bond of PMEMA‐CA can be broken by the glutathione (GSH) in TME, leading to the shedding of PMEMA from the IO surface. Under the dual actions of ROS and GSH in TME (i.e., AND logic gate), SA‐IO‐BQR@PMEMA can be disassembled to release IO, Fe2+/3+, and BQR. In vitro and in vivo results demonstrate the AND logic gate function and mechanism, the high T1 MRI performance and exceptional ferroptosis therapy efficacy for tumors, and the excellent biosafety of SA‐IO‐BQR@PMEMA.This article is protected by copyright. All rights reserved

Furin-Catalyzed Enhanced Magnetic Resonance Imaging Probe for Differential Diagnosis of Malignant Breast Cancers

“…Subsequently, the Δsignal-tonoise ratio (ΔSNR) of MDA-MB-231 and MCF-7 tumor images were quantified. 47 The ΔSNR of T 2 -weighted images was similar at 2 h postinjection of FFG NPs (Figure 5C). A notable detail is that the FFG NP-enhanced T 2 -weighted MRI signals reflected the sMRI information on tumor lesions only, but they cannot image the furin expression in tumor tissues.…”

“…The T 2 signal for MDA-MB-231 and MCF-7 tumors at 2 h quantitatively decreased by 37.7% and 43.3%, respectively, indicating a similar uptake to that of FFG NPs in these two types of tumors (Figure S6B). Subsequently, the Δsignal-to-noise ratio (ΔSNR) of MDA-MB-231 and MCF-7 tumor images were quantified . The ΔSNR of T 2 -weighted images was similar at 2 h postinjection of FFG NPs (Figure C).…”

Immunoantitumor Activity and Oxygenation Effect Based on Iron–Copper-Doped Folic Acid Carbon Dots

“…Chemodynamic therapy (CDT) is based on Fenton or Fenton-like reaction to produce reactive oxygen species to kill cancer cells, − and photothermodynamic therapy (PTT) is based on high temperature to damage cancer cells. Both CDT and PTT induce immunogenic cell death (ICD) in tumor cells, and combination therapy with immune checkpoint blockers effectively inhibits cancer metastasis and recurrence, − showing promising clinical applications.…”

Cysteine Depletion-Initiated Redox Imbalance Evokes Ferroptosis and Pyroptosis for Enhanced Pancreatic Cancer Therapy

“…More than 90% of pancreatic cancers have mutations in the KRAS gene, which makes pancreatic cancer tumor cells highly proliferative and increases intracellular reactive oxygen species (ROS) generation. − To alleviate oxidative stress, cysteine (Cys) uptake programs are upregulated in pancreatic cancer cells, which has been demonstrated by many previous studies. , Glutathione (GSH) and thioredoxin (TXN) redox systems are highly dependent on Cys. , Tumor therapy mediated by GSH depletion has been shown to induce significant oxidative imbalance and ferroptosis. , Meanwhile GSH is synthesized from glycine, glutamate, and Cys via GSH synthase (GS), among which Cys is a rate-limiting step. Additionally, GSH directly influences the function of glutathione peroxidase (GPx), the only cellular coping strategy for lipid peroxidation. − On the other hand, TXN alleviates ROS stress through selenol and thiol, but the synthesis of TXN is also limited by Cys .…”

“…6,7 Tumor therapy mediated by GSH depletion has been shown to induce significant oxidative imbalance and ferroptosis. 8,9 Meanwhile GSH is synthesized from glycine, glutamate, and Cys via GSH synthase (GS), among which Cys is a rate-limiting step. Additionally, GSH directly influences the function of glutathione peroxidase (GPx), the only cellular coping strategy for lipid peroxidation.…”