Targeting cell death pathways for cancer therapy: recent developments in necroptosis, pyroptosis, ferroptosis, and cuproptosis research

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Dec. 8, 2022

Abstract Many types of human cells self-destruct to maintain biological homeostasis and defend the body against pathogenic substances. This process, called regulated cell death (RCD), is important for various activities, including clearance aberrant cells. Thus, RCD pathways represented by apoptosis have increased in importance as a target development cancer medications recent years. However, because tumor show avoidance apoptosis, which causes treatment resistance recurrence, numerous studies been devoted alternative mortality processes, namely necroptosis, pyroptosis, ferroptosis, cuproptosis; these modalities extensively studied shown be crucial therapy effectiveness. Furthermore, evidence suggests that undergoing may alter immunogenicity microenvironment (TME) some extent, rendering it more suitable inhibiting progression metastasis. In addition, other components TME undergo abovementioned forms induce immune attacks on cells, resulting enhanced antitumor responses. Hence, this review discusses molecular processes features cuproptosis effects novel proliferation Importantly, introduces complex affect biology. It also summarizes potential agents nanoparticles or inhibit their therapeutic based from vivo vitro reports clinical trials inducers evaluated treatments patients. Lastly, we summarized impact modulating drug advantages adding modulators over conventional treatments.

Language: Английский

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Chemodynamic Therapy via Fenton and Fenton‐Like Nanomaterials: Strategies and Recent Advances

Small, Journal Year: 2021, Volume and Issue: 18(6)

Published: Nov. 2, 2021

Abstract Chemodynamic therapy (CDT), a novel cancer therapeutic strategy defined as the treatment using Fenton or Fenton‐like reaction to produce •OH in tumor region, was first proposed by Bu, Shi, and co‐workers 2016. Recently, with rapid development of nanomaterials, CDT has attracted tremendous attention because its unique advantages: 1) It is tumor‐selective low side effects; 2) process does not depend on external field stimulation; 3) it can modulate hypoxic immunosuppressive microenvironment; 4) cost low. In addition Fe‐involved strategies, reaction‐mediated strategies have also been proposed, which are based many other metal elements including copper, manganese, cobalt, titanium, vanadium, palladium, silver, molybdenum, ruthenium, tungsten, cerium, zinc. Moreover, combined therapies like chemotherapy, radiotherapy, phototherapy, sonodynamic therapy, immunotherapy for achieving enhanced anticancer effects. Besides, there studies that extend application antibacterial field. This review introduces latest advancements nanomaterials‐involved from 2018 present proposes current limitations well future research directions related

Language: Английский

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Manipulating Intratumoral Fenton Chemistry for Enhanced Chemodynamic and Chemodynamic‐Synergized Multimodal Therapy

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(48)

Published: Sept. 27, 2021

Chemodynamic therapy (CDT) uses the tumor microenvironment-assisted intratumoral Fenton reaction for generating highly toxic hydroxyl free radicals (•OH) to achieve selective treatment. However, limited efficiency restricts therapeutic efficacy of CDT. Recent years have witnessed impressive development various strategies increase reaction. The introduction these reinforcement can dramatically improve treatment CDT and further promote enhanced (ECDT)-based multimodal anticancer treatments. In this review, authors systematically introduce strategies, from their basic working principles, mechanisms representative clinical applications. Then, ECDT-based is discussed, including how integrate emerging accelerating therapy, as well synergistic ECDT other methods. Eventually, future direction challenges therapies are elaborated, highlighting key scientific problems unsolved technical bottlenecks facilitate translation.

Language: Английский

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Glutathione-Depleting Nanomedicines for Synergistic Cancer Therapy

ACS Nano, Journal Year: 2021, Volume and Issue: 15(5), P. 8039 - 8068

Published: May 11, 2021

Cancer cells frequently exhibit resistance to various molecular and nanoscale drugs, which inevitably affects the drugs' therapeutic outcomes. Overexpression of glutathione (GSH) has been observed in many cancer cells, solid evidence corroborated resulting tumor a variety anticancer therapies, suggesting that this biochemical characteristic can be developed as potential target for treatments. The single treatment GSH-depleting agents potentiate responses different cell death stimuli; therefore, an adjunctive strategy, GSH depletion is usually combined with mainstream therapies enhancing Propelled by rapid development nanotechnology, readily constructed into nanomedicines, have shown steep rise over past decade. Here, we review common nanomedicines widely applied synergistic treatments recent years. Some current challenges future perspectives depletion-based are also presented. With understanding structure–property relationship action mechanisms these biomaterials, hope nanotechnology will further realize more effective disease even achieve successful clinical translations.

Language: Английский

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Nanozymes-recent development and biomedical applications

Journal of Nanobiotechnology, Journal Year: 2022, Volume and Issue: 20(1)

Published: Feb. 22, 2022

Nanozyme is a series of nanomaterials with enzyme-mimetic activities that can proceed the catalytic reactions natural enzymes. In field biomedicine, nanozymes are capturing tremendous attention due to their high stability and low cost. Enzyme-mimetic be regulated by multiple factors, such as chemical state metal ion, pH, hydrogen peroxide (H2O2), glutathione (GSH) level, presenting great promise for biomedical applications. Over past decade, multi-functional have been developed various To promote understandings development novel multifunctional nanozymes, we herein provide comprehensive review applications in field. Nanozymes versatile enzyme-like properties briefly overviewed, mechanism application discussed future research. Finally, underlying challenges prospects frontier this review.

Language: Английский

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An Enzyme‐Engineered Nonporous Copper(I) Coordination Polymer Nanoplatform for Cuproptosis‐Based Synergistic Cancer Therapy

Advanced Materials, Journal Year: 2022, Volume and Issue: 34(43)

Published: Sept. 2, 2022

Abstract Cuproptosis, a newly identified form of regulated cell death that is copper‐dependent, offers great opportunities for exploring the use copper‐based nanomaterials inducing cuproptosis cancer treatment. Here, glucose oxidase (GOx)‐engineered nonporous copper(I) 1,2,4‐triazolate ([Cu(tz)]) coordination polymer (CP) nanoplatform, denoted as GOx@[Cu(tz)], starvation‐augmented and photodynamic synergistic therapy developed. Importantly, catalytic activity GOx shielded in scaffold but can be “turned on” efficient depletion only upon glutathione (GSH) stimulation cells, thereby proceeding starvation therapy. The GSH sensitizes cells to GOx@[Cu(tz)]‐mediated cuproptosis, producing aggregation lipoylated mitochondrial proteins, target copper‐induced toxicity. increased intracellular hydrogen peroxide (H 2 O ) levels, due oxidation glucose, activates type I (PDT) efficacy GOx@[Cu(tz)]. vivo experimental results indicate GOx@[Cu(tz)] produces negligible systemic toxicity inhibits tumor growth by 92.4% athymic mice bearing 5637 bladder tumors. This thought first report cupreous nanomaterial capable cuproptosis‐based cancer, which should invigorate studies pursuing rational design efficacious strategies based on cuproptosis.

Language: Английский

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Enhancing the therapeutic efficacy of nanoparticles for cancer treatment using versatile targeted strategies

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Sept. 12, 2022

Poor targeting of therapeutics leading to severe adverse effects on normal tissues is considered one the obstacles in cancer therapy. To help overcome this, nanoscale drug delivery systems have provided an alternative avenue for improving therapeutic potential various agents and bioactive molecules through enhanced permeability retention (EPR) effect. Nanosystems with cancer-targeted ligands can achieve effective tumor cells utilizing cell surface-specific receptors, vasculature antigens high accuracy affinity. Additionally, stimuli-responsive nanoplatforms also been as a promising strategy against tumors, these maintain their stealth feature under conditions, but upon homing cancerous lesions or microenvironment, are responsive release cargoes. In this review, we comprehensively summarize field active number studies context emerging nanoplatform development, discuss how knowledge contribute further improvements clinical practice.

Language: Английский

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Tumor‐Microenvironment‐Activated Reactive Oxygen Species Amplifier for Enzymatic Cascade Cancer Starvation/Chemodynamic /Immunotherapy

Advanced Materials, Journal Year: 2021, Volume and Issue: 34(4)

Published: Oct. 26, 2021

At present, some progress has been made in the field of cancer theranostics based on nanocatalysts (NCs), but achieving precise response to specific tumor microenvironment (TME) remains a major challenge. Herein, TME-responsive upconversion nanoparticles (UCNPs)-based smart UCNPs@Cu-Cys-GOx (UCCG) nanosystem is engineered, which combines natural enzymes and nanozymes so as amplify reactive oxygen species (ROS) generation situ for starvation/chemodynamic/immunotherapy. One biggest merits this material that it can be preserved inert (off) normal tissues, only TME specifically activated (on) through series enzymatic cascades boost ROS production via strategy open source (H2 O2 self-supplying ability) reduce expenditure (glutathione (GSH) consuming ability). More importantly, enhanced oxidative stress by UCCG NCs reverses immunosuppressive TME, facilitates antitumor immune responses. Meanwhile, starvation/chemodynamic synergistic therapy triggered combined with PD-L1 antibody effectively inhibits growth primary tumors metastasis. In addition, UCNPs present luminescence enhancement, exploited visualize reinforced real time. Collectively, work provides an original method devising exploitation UCNPs-based catalytic immunotherapy.

Language: Английский

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Enhanced Chemodynamic Therapy by Cu–Fe Peroxide Nanoparticles: Tumor Microenvironment-Mediated Synergistic Fenton Reaction

ACS Nano, Journal Year: 2022, Volume and Issue: 16(2), P. 2535 - 2545

Published: Jan. 26, 2022

An urgent need in chemodynamic therapy (CDT) is to achieve high Fenton catalytic efficiency at small doses of CDT agents. However, simple general promotion the reaction increases risk damaging normal cells along with cancer cells. Therefore, a tailored strategy selectively enhance reactivity tumors, for example, by taking advantage characteristics tumor microenvironment (TME), demand. Herein, heterogeneous system based on copper–iron peroxide nanoparticles (CFp NPs) designed TME-mediated synergistic therapy. CFp NPs degrade under mildly acidic conditions TME, self-supply H2O2, and released Cu Fe ions, their larger portions lower oxidation states, cooperatively facilitate hydroxyl radical production through highly efficient loop an excellent therapeutic efficacy. This distinct from previous systems that synergism closely coupled Cu+-assisted conversion Fe3+ Fe2+ rather than independent actions. As result, almost complete ablation tumors minimal treatment dose demonstrated without aid any other modality. Furthermore, generate O2 during catalysis exhibit TME-responsive T1 magnetic resonance imaging contrast enhancement, which are useful alleviating hypoxia vivo monitoring respectively.

Language: Английский

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Strategies for enhancing cancer chemodynamic therapy performance

Exploration, Journal Year: 2022, Volume and Issue: 2(2)

Published: March 7, 2022

Chemodynamic therapy (CDT) has emerged to be a frontrunner amongst reactive oxygen species-based cancer treatment modalities. CDT utilizes endogenous H

Language: Английский

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