Mechanical stimuli-driven cancer therapeutics

Chemical Society Reviews, Journal Year: 2022, Volume and Issue: 52(1), P. 30 - 46

Published: Dec. 13, 2022

Mechanical stimulation utilizing deep tissue-penetrating and focusable energy sources, such as ultrasound magnetic fields, is regarded an emerging patient-friendly effective therapeutic strategy to overcome the limitations of conventional cancer therapies based on fundamental external stimuli light, heat, electricity, radiation, or microwaves. Recent efforts have suggested that mechanical stimuli-driven therapy (henceforth referred "mechanical therapy") could provide a direct effect intelligent control augment other anti-cancer systems synergistic combinational treatment. This review article highlights latest advances in present novel perspective principles ultrasound- field-mediated forces, including compression, tension, shear force, torque, can be generated cellular microenvironment using stimuli-activated functional materials. Additionally, this will shed light inspire future research pursue development magnetic-field-activated materials their applications field.

Language: Английский

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Recent advances in anti-multidrug resistance for nano-drug delivery system

Drug Delivery, Journal Year: 2022, Volume and Issue: 29(1), P. 1684 - 1697

Published: May 26, 2022

Chemotherapy for tumors occasionally results in drug resistance, which is the major reason treatment failure. Higher doses could improve therapeutic effect, but higher toxicity limits further treatment. For overcoming functional nano-drug delivery system (NDDS) has been explored to sensitize anticancer drugs and decrease its side effects, are applied combating multidrug resistance (MDR) via a variety of mechanisms including bypassing efflux, controlling release, disturbing metabolism. This review starts with brief report on MDR causes. Furthermore, we searched papers from NDDS introduced recent advances sensitizing chemotherapeutic against tumors. Finally, concluded that was based several mechanisms, looked forward future this field.

Language: Английский

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A Vanadium-Based Nanoplatform Synergizing Ferroptotic-like Therapy with Glucose Metabolism Intervention for Enhanced Cancer Cell Death and Antitumor Immunity

ACS Nano, Journal Year: 2023, Volume and Issue: 17(12), P. 11537 - 11556

Published: June 5, 2023

Ferroptosis activation has been considered a mighty weapon for cancer treatment, and growing attention is being paid to reinforcing tumor cells' sensitivity ferroptosis. However, the existence of certain ferroptosis resistance mechanisms, especially abnormal metabolism cells, long underestimated. We propose an enhanced ferroptosis-activating pattern via regulating glycometabolism construct nanoplatform named PMVL, which composed lonidamine (LND)-loaded tannic acid coordinated vanadium oxides with camouflage PD-L1 inhibiting peptide-modified cell membrane. This work reveals that mixed valence (VIV VV) in PMVL triggers due self-cyclic alteration V, process generates •OH lipid peroxide accumulation → depletes glutathione (GSH) peroxidase (GPX4) deactivation (VV VIV). Notably, LND strengthens by dual suppression glycolysis (decreasing ATP supply) pentose phosphate pathway NADPH production), causing anabatic GSH consumption. Besides, inhibited less intracellular lactic alleviates acidity microenvironment, preventing immunosuppressive M2 macrophage polarization. In vitro vivo data demonstrate glycometabolism-intervention-enhanced boosted immunity activation, potentially providing opportunities possibilities synergetic therapy.

Language: Английский

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Enhancing Tumor Therapy of Fe(III)-Shikonin Supramolecular Nanomedicine via Triple Ferroptosis Amplification

ACS Applied Materials & Interfaces, Journal Year: 2022, Volume and Issue: 14(33), P. 37540 - 37552

Published: Aug. 9, 2022

Ferroptosis has been considered as a promising pathway to overcome apoptosis-induced tumor chemoresistance. However, the antitumor efficacy of ferroptosis-inducing agents is still limited because complexity and diversity microenvironments. Herein, we demonstrate triple ferroptosis amplification strategy for therapy by associating iron-based nanocarriers, molecular drugs, H2O2-producing enzymes. Fe(III)-Shikonin (FeShik) metal-polyphenol-coordinated networks are employed load inducer sorafenib (SRF) inside glucose oxidase (GOx) outside, thus producing SRF@FeShik-GOx supramolecular nanomedicines (SNs). After delivering into glutathione (GSH)-overexpressed cells, FeShik will disassemble release Fe2+ induce cell death via ferroptosis. At same time, GOx executes its catalytic activity produce an acid environment plenty H2O2 stimulating •OH generation Fenton reaction. Moreover, SRF suppress biosynthesis GSH inhibiting system Xc-, further deactivating enzymatic peroxidase 4 (GPX4). Up-regulation oxidative stress level down-regulation GPX4 expression can dramatically accelerate accumulation lethal lipid peroxides, leading cells. The current that utilizes both nanocarriers cargoes provides enhance ferroptosis-based therapy.

Language: Английский

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Inhalable Biomimetic Protein Corona-Mediated Nanoreactor for Self-Amplified Lung Adenocarcinoma Ferroptosis Therapy

ACS Nano, Journal Year: 2022, Volume and Issue: 16(5), P. 8370 - 8387

Published: May 15, 2022

Ferroptosis therapy by catalyzing the Fenton reaction has emerged as a promising tumor elimination strategy for lung adenocarcinoma (ADC). However, unsatisfactory efficiency, strong intracellular antioxidant system, and insufficient drug accumulation limits ferroptosis therapeutic effect. To address these issues, an inhalable nanoreactor was proposed spontaneously adsorbing biomimetic protein corona (PC) composed of matrix metalloproteinase 2 responsive gelatin glutamate (Glu) on surface cationic nanostructured lipid carriers (NLC) core loaded with ferrocene (Fc) fluvastatin. The prepared Fc-NLC(F)@PC could be nebulized into lesions 2.6 times higher boost peroxide production 3.2 to enhance therapy. Mechanically, fluvastatin proved inhibit monocarboxylic acid transporter 4 mediated lactate efflux, inducing acidosis Fc-catalyzing reactive oxygen species production, while extracellular elevating Glu concentration found xCT (system Xc–) functions further collapse system glutathione synthesis suppression. Mitochondrial dysfunction cell membrane damage were involved in nanoreactor-driven ferroptotic death process. enhanced antitumor effects combination confirmed orthotopic ADC model. Overall, highlights pulmonary delivery approach local treatment underscores great potential

Language: Английский

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Amphiphilic Dendrimer Doping Enhanced pH‐Sensitivity of Liposomal Vesicle for Effective Co‐delivery toward Synergistic Ferroptosis–Apoptosis Therapy of Hepatocellular Carcinoma

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(6)

Published: Jan. 19, 2023

Ferroptosis, characterized by the accumulation of reactive oxygen species and lipid peroxides, has emerged as an attractive strategy to reverse drug resistance. Of particular interest is ferroptosis-apoptosis combination therapy for cancer treatment. Herein, a nanoplatform reported effective co-delivery anticancer sorafenib (S) ferroptosis inducer hemin (H), toward synergistic advanced hepatocellular carcinoma (HCC) proof-of-concept study. Liposome excellent delivery system; however, it not sufficiently responsive acidic tumor microenvironment (TME) tumor-targeted delivery. The pH-sensitive vesicles are therefore developed (SH-AD-L) incorporating amphiphilic dendrimers (AD) into liposomes controlled pH-stimulated release in TME, thanks protonation numerous amine functionalities AD. Importantly, SH-AD-L only blocked glutathione synthesis disrupt antioxidant system, but also increased intracellular Fe2+ ·OH concentrations amplify oxidative stress, both which contribute enhanced ferroptosis. Remarkably, high levels augmented sorafenib-mediated apoptosis cells. This study demonstrates efficacy therapy, well promise AD-doped TME-responsive treat HCC.

Language: Английский

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DNAzyme‐Mediated Cascade Nanoreactor for Cuproptosis‐Promoted Pancreatic Cancer Synergistic Therapy

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(28)

Published: Aug. 7, 2023

Abstract Cuproptosis, a kind of newly recognized cell death modality, shows enormous prospect in cancer treatment. The inducer cuproptosis has more advantages tumor therapy, especially that can trigger and chemodynamic therapy (CDT) simultaneously. However, is restricted to the deficiency intracellular copper ions nonspecific delivery copper‐based ionophores. Therefore, high level delivery, responsive release, utilizing synergistic‐function become key on cuproptosis‐based oncotherapy. In this work, cascade nanosystem constructed for enhanced CDT. weak acidic environment cells, DNA, zinc ions, Cu + release from nanosystem. Since having superior performance mediating both Fenton‐like reaction cuproptosis, released induces CDT efficiently, accompanied by 2+ generation. Then be converted into partially glutathione (GSH) supply loop ensure synergistic action. Meanwhile, consumption GSH also contributes return. Finally, DNA Zn form DNAzyme shear catalase‐related RNA, resulting accumulation hydrogen peroxide further enhancing combination therapy. These results provide promising nanotherapeutic platform may inspire design potential treatment based cuproptosis.

Language: Английский

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GSH/APE1 Cascade-Activated Nanoplatform for Imaging Therapy Resistance Dynamics and Enzyme-Mediated Adaptive Ferroptosis

ACS Nano, Journal Year: 2023, Volume and Issue: 17(14), P. 13792 - 13810

Published: July 17, 2023

Ferroptosis, as a type of programmed cell death process, enables effective damage to various cancer cells. However, we discovered that persistent oxidative stress during ferroptosis can upregulate the apurinic/apyrimidinic endonuclease 1 (APE1) protein induces therapeutic resistance ("ferroptosis resistance"), resulting in an unsatisfactory treatment outcome. To address APE1-induced resistance, developed GSH/APE1 cascade activated nanoplatform (GAN). Specifically, GAN is self-assembled by DNA-functionalized ultrasmall iron oxide nanoparticles and further loaded with drug molecules (drug-GAN). GSH-triggered disassembly "turn on" catalysis induce efficient lipid peroxidation (LPO) for toward tumor, which could APE1 expression. Subsequently, upregulated trigger accurate release overcoming inducing recovery near-infrared fluorescence imaging dynamics APE1. Importantly, adaptive overcome adverse effects upregulation boosting intracellular ROS yield increasing DNA damage, offset APE1's functions antioxidant repair, thus leading ferroptosis. Moreover, overexpressed GSH tumor stimuli, specificity greatly improved, minimized nonspecific activation excessive normal tissues. Furthermore, switchable MRI contrast from negative positive sync activation, beneficial monitoring process. Therefore, this adapted not only deliver GSH/APE1-activated peroxide mediated synergistic therapy but also provided MRI/dual-channel signal release, vivo, high-specificity high-efficiency therapy.

Language: Английский

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Antitumor Effects of a Distinct Sonodynamic Nanosystem through Enhanced Induction of Immunogenic Cell Death and Ferroptosis with Modulation of Tumor Microenvironment

JACS Au, Journal Year: 2023, Volume and Issue: 3(5), P. 1507 - 1520

Published: May 9, 2023

Sonodynamic therapy (SDT) holds great promise to be applied for cancer in clinical settings. However, its poor therapeutic efficacy has limited applications owing the apoptosis-resistant mechanism of cells. Moreover, hypoxic and immunosuppressive tumor microenvironment (TME) also weakens immunotherapy solid tumors. Therefore, reversing TME remains a formidable challenge. To circumvent these critical issues, we developed an ultrasound-augmented strategy regulate by utilizing HMME-based liposomal nanosystem (HB liposomes), which can synergistically promote induction ferroptosis/apoptosis/immunogenic cell death (ICD) initiate reprograming TME. The RNA sequencing analysis demonstrated that apoptosis, hypoxia factors, redox-related pathways were modulated during treatment with HB liposomes under ultrasound irradiation. vivo photoacoustic imaging experiment showed enhanced oxygen production TME, alleviated hypoxia, helped overcome tumors, consequently improving SDT efficiency. More importantly, extensively induced ICD, resulting T-cell recruitment infiltration, normalizes facilitates antitumor immune responses. Meanwhile, system combined PD1 checkpoint inhibitor achieves superior synergistic inhibition. Both vitro results indicate act as sonodynamic adjuvant is able induce ferroptosis/apoptosis/ICD via generated lipid-reactive oxide species reprogram due ICD induction. This integrating supply, reactive generation, excellent effective modulation efficient therapy.

Language: Английский

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Superoxide Dismutase‐Like Regulated Fe/Ppa@PDA/B for Synergistically Targeting Ferroptosis/Apoptosis to Enhance Anti‐Tumor Efficacy

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(29)

Published: July 24, 2023

The cell apoptosis pathway of sonodynamic therapy (SDT) is usually blocked, resulting in limited therapeutic efficacy, therefore, the development new methods for sensitizing targeted ferroptosis and promoting great significance to improve anti-tumor efficacy SDT. Herein, mesoporous Fe3 O4 nanoparticles (NPs) are synthesized loading pyropheophorbide-a (ppa), surface-coated by polydopamine (PDA) further anchored with tumor-targeting moieties biotin obtain Fe/ppa@PDA/B NPs. displayes pH/ultrasound (US) responsive release properties, magnetic resonance imaging (MRI) functions. Moreover, NPs as Fe source ferroptosis, enhances sensitivity consuming glutathione (GSH) producing hydroxyl radical (OH). quinone groups PDA layer on own free electrons, which led effective superoxide dismutase (SOD) action through anion (O2- ) disproportionation hydrogen peroxide (H2 O2 oxygen (O2 ), thus, overcame hypoxia SDT promoted ·OH generation ions under US trigger, synergistically improves enhance both vitro vivo. strategy synergistic induce GSH depletion self-sufficient regulated SOD provides a idea enhancing efficacy.

Language: Английский

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