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. 2021 Jul 13;9:629054. doi: 10.3389/fchem.2021.629054

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Copyright © 2021 Ali, Shah, Ullah, Zhou, Guo, Ovais, Tan and Rui.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Schematics (A) illustration of the anticancer drug (DOX) conjugating into polymer encapsulated superparamagnetic NPs and the overall mechanism of cancer cell killing by synergistic therapy under applied Alternating Magnetic Field (AMF). Copyright 2017, American chemical Society (Thorat et al., 2017) (B) Representation of the mechanism of improved EPR effect and accumulation of ultrafine iron oxide nanoparticles (uIONPs) inside tumor with a bright-to-dark T₁-T₂ MRI contrast transition. uIONPs quickly and easily extravasate from dripping tumor vessels into a tumor with favorable kinetics, then self-assemble into clusters in the tumor microenvironment at a low pH (6.5), limiting clustered uIONP intravasation back into circulation (C) Optical images of T₁-and T₂-weighted MRI of a mouse with orthotopic 4T1 tumors pre- and post i.v administration of uIONP at different time intervals (Wang L. et al., 2017). Copyright 2017, American Chemical Society (D) Tumor-specific nanotheranostics NQ-Cy@Fe&GOD for in situ real-time reporting of Fenton-based dose-dependent •OH generation: 1) Owing to the passive and active targeting ability, NQ-Cy@Fe&GOD are delivered into tumor sites, along with the enhanced MRI signal; 2) Turn-on NIR fluorescence signal at 830 nm (NIR-1) is observed in synchronous with its intracellular dissociation for evaluating the released dose of Fenton agents. Concurrently, the released GOD catalyzes glucose to produce H₂O₂; 3) Subsequently, high-level •OH is generated by IONPs-based Fenton reaction with intratumor H₂O₂, thereby triggering the activation of Keap1-Nrf2 pathway for high-level overexpression of NQO1 enzyme, which is timely supervised by a new emission at 650 nm (NIR-2). Overall, this nanocomposite bridges dual-channel NIR imaging and MRI modality, thereby uniting spatial and temporal resolution on dose-dependent •OH therapeutic feedback (E) Imaging of the bio-distribution with MRI signal by intravenous injection. T₁-Weighted (A,B) and T₂-Weighted (C,D) MRI of tumor-bearing mice after experiencing a magnetic field at after the intravenous administration of NQ-Cy@Fe&GOD at different time intervals. Copyright 2020, John Wiley and Sons (Ma et al., 2020).