A Forward Vision for Chemodynamic Therapy: Issues and Opportunities

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(7)

Published: Jan. 17, 2023

Abstract Since the insight to fuse Fenton chemistry and nanomedicine into cancer therapy, great signs of progress have been made in field chemodynamic therapy (CDT). However, exact mechanism CDT is obscured by unique tumor chemical environment inevitable nanoparticle‐cell interactions, thus impeding further development. In this Scientific Perspective, significance clarified, complex deconstructed primitive biological research directions based on kinetics signaling pathways are discussed detail. Moreover, beneficial outlooks presented enlighten evolution next‐generation CDT. Hopefully, Perspective can inspire new ideas advances for provide a reference breaking down interdisciplinary barriers nanomedicine.

Language: Английский

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One-Step Integration of Tumor Microenvironment-Responsive Calcium and Copper Peroxides Nanocomposite for Enhanced Chemodynamic/Ion-Interference Therapy

ACS Nano, Journal Year: 2021, Volume and Issue: 16(1), P. 617 - 630

Published: Dec. 27, 2021

Recently, various metal peroxide nanomaterials have drawn increasing attention as an efficient hydrogen (H2O2) self-supplying agent for enhanced tumor therapy. However, a single kind of is insufficient to achieve more effective antitumor performance. Here, hyaluronic acid modified calcium and copper peroxides nanocomposite has been synthesized by simple one-step strategy. After accumulation at the site due permeability retention (EPR) effect specific recognition hyaluronate with CD44 protein on surface cells, plenty Ca2+, Cu2+, H2O2 can be simultaneously released in hyaluronidase overexpressed microenvironment (TME), generating abundant hydroxyl radical through Fenton-type reaction between Cu2+ assistance glutathione depletion. Overloaded Ca2+ lead mitochondria injury thus enhance oxidative stress cells. Moreover, unbalanced transport channel caused further promote calcification necrosis, which generally defined ion-interference As result, synergistic Fenton-like dysfunction ROS generation performed. Therefore, TME-responsive based integration successfully established exhibits satisfactory efficiency than any peroxide.

Language: Английский

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Copper-based metal–organic frameworks for biomedical applications

Advances in Colloid and Interface Science, Journal Year: 2022, Volume and Issue: 305, P. 102686 - 102686

Published: April 29, 2022

Language: Английский

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Elucidating the Mechanistic Origin of a Spin State-Dependent FeN_x–C Catalyst toward Organic Contaminant Oxidation via Peroxymonosulfate Activation

Environmental Science & Technology, Journal Year: 2021, Volume and Issue: 56(2), P. 1321 - 1330

Published: Dec. 23, 2021

Atomically dispersed metals on nitrogen-doped carbon matrices have attracted extensive interest in the removal of refractory organic pollutants. However, a thorough exploration particular structure for each active site and specific effects these sites still remains elusive. Herein, an Fe-pyridinic N4 single-atom catalyst (FeNx-C) was constructed using facile pyrolysis strategy, it exhibited superior catalytic activity peroxymonosulfate (PMS) activation toward contaminant oxidation. The various Fe species relative amounts FeNx-C were validated X-ray absorption spectroscopy 57Fe Mössbauer spectroscopy, which showed critical dependencies precursor ratio calcination temperature. positive correlations between content high-spin state (FeII FeIII) performance found to determine reactive generation electron transfer pathway FeNx-C/PMS system. Moreover, theoretical calculation results revealed that FeII-N4 (S = 2) tends activate PMS form sulfate hydroxyl radicals via one-electron process, while FeIII-N4 moiety 5/2) is prone high-valent iron with lower free energy. Benefiting from finely tuned sites, achieved favorable applicability actual wastewater treatment efficient resistance common water matrix. present work advances mechanistic understanding spin state-dependent persulfate catalysts provides guidance design based descriptions.

Language: Английский

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Copper-Based Metal–Organic Framework Overcomes Cancer Chemoresistance through Systemically Disrupting Dynamically Balanced Cellular Redox Homeostasis

Journal of the American Chemical Society, Journal Year: 2022, Volume and Issue: 144(11), P. 4799 - 4809

Published: Feb. 22, 2022

Chemodrug resistance is a major reason accounting for tumor recurrence. Given the mechanistic complexity of chemodrug resistance, molecular inhibitors and targeting drugs often fail to eliminate drug-resistant cancer cells, sometimes even promote chemoresistance by activating alternative pathways. Here, exploiting biochemical fragility high-level but dynamically balanced cellular redox homeostasis in we design nanosized copper/catechol-based metal-organic framework (CuHPT) that effectively disturbs this tilting balance toward oxidative stress. Within CuHPT starts disassembly triggered persistent consumption glutathione (GSH). simultaneously releases two structural elements: catechol ligands reductive copper ions (Cu+). Both them cooperatively function amplify production intracellular radical species (ROS) via auto-oxidation Fenton-like reactions through exhausting GSH. By drastically heightening stress, exhibits selective potent cytotoxicity multiple cells. Importantly, inhibits vivo growth doubles survival time tumor-bearing mice. Thus, along with CuHPT's good biocompatibility, our biochemical, cell biological, preclinical animal model data provide compelling evidence supporting notion copper-based MOF predesigned smart therapeutic against cancers precisely deconstructing their homeostasis.

Language: Английский

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Ferroptosis‐Enhanced Cancer Immunity by a Ferrocene‐Appended Iridium(III) Diphosphine Complex

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(16)

Published: Dec. 29, 2021

Ferroptosis is a programmed cell death pathway discovered in recent years, and ferroptosis-inducing agents have great potential as new antitumor candidates. Here, we report IrIII complex (Ir1) containing ferrocene-modified diphosphine ligand that localizes lysosomes. Under the acidic environments of lysosomes, Ir1 can effectively catalyze Fenton-like reaction, produce hydroxyl radicals, induce lipid peroxidation, down-regulate glutathione peroxidase 4, result ferroptosis. RNA sequencing analysis shows significantly affect pathways related to ferroptosis cancer immunity. Accordingly, immunogenic cells suppress tumor growth vitro, regulate T activity immune microenvironments vivo. In conclusion, show small molecules with capabilities for effective immunotherapy.

Language: Английский

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Harnessing Nanomaterials for Cancer Sonodynamic Immunotherapy

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(33)

Published: March 7, 2023

Abstract Immunotherapy has made remarkable strides in cancer therapy over the past decade. However, such emerging still suffers from low response rates and immune‐related adverse events. Various strategies have been developed to overcome these serious challenges. Therein, sonodynamic (SDT), as a non‐invasive treatment, received ever‐increasing attention especially treatment of deep‐seated tumors. Significantly, SDT can effectively induce immunogenic cell death trigger systemic anti‐tumor immune response, termed immunotherapy. The rapid development nanotechnology revolutionized effects with robust induction. As result, more innovative nanosonosensitizers synergistic modalities are established superior efficacy safe profile. In this review, recent advances immunotherapy summarized particular emphasis on how be explored harness for amplifying response. Moreover, current challenges field prospects its clinical translation also presented. It is anticipated that review provide rational guidance facilitate nanomaterials‐assisted immunotherapy, helping pave way next‐generation eventually achieve durable patients.

Language: Английский

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Recent advances on modulation of H2O2 in tumor microenvironment for enhanced cancer therapeutic efficacy

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 481, P. 215049 - 215049

Published: Feb. 9, 2023

Language: Английский

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Coordinating the Mechanisms of Action of Ferroptosis and the Photothermal Effect for Cancer Theranostics

Angewandte Chemie International Edition, Journal Year: 2021, Volume and Issue: 61(13)

Published: Dec. 21, 2021

Combination therapy based on different mechanisms of cell death has shown promise in tumor therapy. However, when modalities are integrated, the maximum synergy therapeutic effects is often lacking design. Herein, we report a cancer theranostic nanomedicine formula developed by considering action ferroptosis and photothermal effect combination The croconaine molecule was encapsulated as both converter an iron-chelating agent with BSA, thus leading to biocompatible stable Cro-Fe@BSA nanoparticles (NPs). NPs milieu showed activated enhanced radical formation owing temperature-dependent Fenton reaction kinetics, while during turn prevented heat-induced heat shock proteins self-protection mechanism cells response heat. activatable photoacoustic magnetic resonance imaging performance also enabled safe reliable theranostics.

Language: Английский

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A Ferrocene‐Functionalized Covalent Organic Framework for Enhancing Chemodynamic Therapy via Redox Dyshomeostasis

Small, Journal Year: 2021, Volume and Issue: 17(32)

Published: July 3, 2021

Chemodynamic therapy (CDT), which induces cell death by decomposing high levels of H2 O2 in tumor cells into highly toxic ·OH, is recognized as a promising antineoplastic approach. However, current CDT approaches are often restricted the controlled and upregulated cellular antioxidant defense. To enhance ·OH-induced damage CDT, covalent organic framework (COF)-based, ferrocene (Fc)- glutathione peroxidase 4 (GPX4) inhibitor-loaded nanodrug, RSL3@COF-Fc (2b), fabricated. The obtained 2b not only promotes situ Fenton-like reactions to trigger ·OH production cells, but also attenuates repair mechanisms under oxidative stress via irreversible GPX4 inhibition. As result, these two synergistically result massive lipid peroxide accumulation, subsequent damage, ultimately ferroptosis, while being limited intracellular glutathione. It believed that this research provides paradigm for enhancing reactive oxygen species-mediated oncotherapy through redox dyshomeostasis may provide new insights developing COF-based nanomedicine.

Language: Английский

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