Self‐Destructive Copper Carriers Induce Pyroptosis and Cuproptosis for Efficient Tumor Immunotherapy Against Dormant and Recurrent Tumors

Advanced Materials, Год журнала: 2023, Номер 36(8)

Опубликована: Окт. 11, 2023

Abstract Activating the strong immune system is a key initiative to counteract dormant tumors and prevent recurrence. Herein, self‐destructive multienzymatically active copper‐quinone‐GOx nanoparticles (abbreviated as CQG NPs) have been designed induce harmonious balanced pyroptosis cuproptosis using “Tai Chi mindset” awaken response for suppressing recurrent tumors. This cleverly material can disrupt antioxidant defense mechanism of tumor cells by inhibiting nuclear factor‐erythroid 2‐related factor 2 (NRF2)‐quinone oxidoreductase 1 (NQO1) signaling pathway. Furthermore, combined with its excellent multienzyme activity, it activates NOD‐like receptor protein 3 (NLRP3)‐mediated pyroptosis. Meanwhile, be triggered copper ions released from disintegration NPs sensitivity cancer enhanced through depletion endogenous chelators via Michael addition reaction between glutathione (GSH) quinone ligand, oxygen production catalase‐like reaction, starvation‐induced glucose deficiency. More importantly, NPs‐induced promote immunosuppressive microenvironment (TME) remodeling, enhance infiltration into tumor, activate robust systemic immunity. Collectively, this study provides new strategy resist dormancy, recurrence, improve clinical prognosis

Язык: Английский

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Single-Site Nanozymes with a Highly Conjugated Coordination Structure for Antitumor Immunotherapy via Cuproptosis and Cascade-Enhanced T Lymphocyte Activity

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(6), С. 3675 - 3688

Опубликована: Фев. 2, 2024

The extracellular matrix (ECM) in the tumor microenvironment (TME) and upregulated immune checkpoints (ICs) on antitumor cells impede infiltration killing effect of T cells, creating an immunosuppressive TME. Herein, a cholesterol oxidase (CHO) lysyl inhibitor (LOX-IN-3) co-delivery copper-dibenzo-[g,p]chrysene-2,3,6,7,10,11,14,15-octaol single-site nanozyme (Cu-DBCO/CL) was developed. conjugated organic ligand well-distributed Cu-O4 sites endow Cu-DBCO with unique redox capabilities, enabling it to catalyze O2 H2O2 ·O2– ·OH. This surge reactive oxygen species (ROS) leads impaired mitochondrial function insufficient ATP supply, impacting copper-transporting ATPase-1 causing dihydrolipoamide S-acetyltransferase oligomerization-mediated cuproptosis. Moreover, multiple ROS storms glutathione peroxidase 4 depletion also induce lipid peroxidation trigger ferroptosis. Simultaneously, ROS-triggered release LOX-IN-3 reshapes ECM by inhibiting activity further enhances cytotoxic lymphocytes (CD8+ cells). CHO-triggered not only increases ·OH generation but downregulates expression ICs such as PD-1 TIM-3, restoring tumor-infiltrating CD8+ cells. Therefore, Cu-DBCO/CL exhibits efficient properties activating potent response cascade-enhanced cell viability. More importantly, remodeling could suppress metastasis proliferation In short, this nanoremodeler can greatly enhance enhancing immunogenicity, ECM, downregulating ICs, thus achieving effective inhibition growth metastasis.

Язык: Английский

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Programmed Targeting Pyruvate Metabolism Therapy Amplified Single‐Atom Nanozyme‐Activated Pyroptosis for Immunotherapy

Advanced Materials, Год журнала: 2024, Номер 36(24)

Опубликована: Фев. 7, 2024

Abstract Increasing cellular immunogenicity and reshaping the immune tumor microenvironment (TME) are crucial for antitumor immunotherapy. Herein, this work develops a novel single‐atom nanozyme pyroptosis initiator: UK5099 pyruvate oxidase (POx)‐co‐loaded Cu‐NS (Cu‐NS@UK@POx), that not only trigger through cascade biocatalysis to boost of cells, but also remodel immunosuppressive TME by targeting metabolism. By replacing N with weakly electronegative S, original spatial symmetry Cu‐N 4 electron distribution is changed enzyme‐catalyzed process effectively regulated. Compared spatially symmetric nanozymes (Cu‐N SA), S‐doped asymmetric (Cu‐NS SA) exhibit stronger activities, including peroxidase (POD), nicotinamide adenine dinucleotide (NADH) (NOx), L ‐cysteine (LCO), glutathione (GSHOx), which can cause enough reactive oxygen species (ROS) storms pyroptosis. Moreover, synergistic effect SA, UK5099, POx target metabolism, improves increases degree This study provides two‐pronged treatment strategy significantly activate immunotherapy effects via ROS storms, NADH/glutathione/ consumption, oxidation, lactic acid (LA)/ATP depletion, triggering regulating broad vision expanding

Язык: Английский

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Nanotechnology Reprogramming Metabolism for Enhanced Tumor Immunotherapy

ACS Nano, Год журнала: 2024, Номер 18(3), С. 1846 - 1864

Опубликована: Янв. 5, 2024

Mutation burden, hypoxia, and immunoediting contribute to altered metabolic profiles in tumor cells, resulting a microenvironment (TME) characterized by accumulation of toxic metabolites depletion various nutrients, which significantly hinder the antitumor immunity via multiple mechanisms, hindering efficacy immunotherapies. In-depth investigation mechanisms underlying these phenomena are vital for developing effective drugs therapies, while therapeutic effects metabolism-targeting restricted off-target toxicity toward effector immune cells high dosage-mediated side effects. Nanotechnologies, exhibit versatility plasticity targeted delivery metabolism modulation, have been widely applied boost immunometabolic therapies strategies, including targeting pathways. In this review, recent advances understanding roles cell both immunoevasion immunosuppression reviewed, nanotechnology-based reprogramming strategies enhanced immunotherapies discussed.

Язык: Английский

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Novel PdPtCu Nanozymes for Reprogramming Tumor Microenvironment to Boost Immunotherapy Through Endoplasmic Reticulum Stress and Blocking IDO‐Mediated Immune Escape

Small, Год журнала: 2023, Номер 19(44)

Опубликована: Июль 2, 2023

Breaking immunosuppressive tumor microenvironment (TME) has unique effects on inhibiting growth and recurrence. Here, an endoplasmic reticulum (ER) targeted PdPtCu nanozyme (PNBCTER ) is prepared to boost immunotherapy. First, PNBCTER three kinds of enzyme activities, including catalase (CAT), glutathione oxidase (GSHOx), peroxidase (POD)-like which can reshape the TME. Second, kills cells by photodynamic therapy (PDT) photothermal (PTT). Third, guided TER , not only realizes combination PDT, PTT chemodynamic (CDT), but also damages ER actives antitumor immune response, breaks through blockade Finally, NLG919 blocks tryptophan/kynurenine escape pathway reverses The strategy that reshaping TME catalysis breaking immunosuppression provides a novel way for application in tumor.

Язык: Английский

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Advantages of Nanomedicine in Cancer Therapy: A Review

ACS Applied Nano Materials, Год журнала: 2023, Номер 6(24), С. 22594 - 22610

Опубликована: Дек. 4, 2023

Nanomedicines, emerging as an innovative category of cancer therapeutics, have garnered increasing attention from both researchers and the broader public. However, despite this surge in interest, a focused comprehensive discussion highlighting their distinct advantages over small molecule drugs remains conspicuously absent. This knowledge gap not only piques curiosity general audience but also leaves engaged these investigations with partial insights, rather than understanding. deficiency represents critical juncture that demands earnest consideration. In light context, present study endeavors to consolidate elucidate unique merits nanomedicines, particularly contrast traditional drugs, within realm treatment. We meticulously summarized 14 nanomedicine, alongside recent advanced applications, special focus on past three years. Our objective is 2-fold: first, provide clear understanding facilitates precise design second, offer nonspecialists accessible platform for grasping concepts establishing strong foundation widespread awareness. essence, our aims bridge knowledge, shedding unparalleled potential nanomedicines therapy, we believe findings hold great promise advancing scientific research public field.

Язык: Английский

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Mitochondria-targeted fluorophores for in vivo NIR-II imaging-guided PDT/PTT

Chemical Communications, Год журнала: 2023, Номер 59(52), С. 8127 - 8130

Опубликована: Янв. 1, 2023

A simple yet powerful D-A type-based NIR-II fluorophore (MTF) with mitochondria targeting was constructed. This mitochondrial dye MTF exhibited not only a photothermal effect but also photodynamic performance, and further fabricated DSPE-mPEG to generate nanodots for in vivo experiments, achieving strong fluorescence tracing of tumors impressive image-guided therapy (PDT) (PTT).

Язык: Английский

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Recent Advances in Reprogramming Strategy of Tumor Microenvironment for Rejuvenating Photosensitizers‐Mediated Photodynamic Therapy

Small, Год журнала: 2023, Номер 20(16)

Опубликована: Ноя. 28, 2023

Abstract Photodynamic therapy (PDT) has recently been considered a potential tumor due to its time‐space specificity and non‐invasive advantages. PDT can not only directly kill cells by using cytotoxic reactive oxygen species but also induce an anti‐tumor immune response causing immunogenic cell death of cells. Although it exhibits promising prospect in treating tumors, there are still many problems be solved practical application. Tumor hypoxia immunosuppressive microenvironment seriously affect the efficacy PDT. The hypoxic is mainly abnormal vascular matrix around tumor, metabolism, influence various immunosuppressive‐related their expressed molecules. Thus, reprogramming (TME) great significance for rejuvenating This article reviews latest strategies PDT, from regulating matrix, interfering with related factors reverse microenvironment. These provide valuable information better understanding TME guide development next‐generation multifunctional nanoplatforms

Язык: Английский

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In Situ Formed Microalgae-Integrated Living Hydrogel for Enhanced Tumor Starvation Therapy and Immunotherapy through Photosynthetic Oxygenation

Nano Letters, Год журнала: 2024, Номер 24(12), С. 3801 - 3810

Опубликована: Март 13, 2024

The effectiveness of various cancer therapies for solid tumors is substantially limited by the highly hypoxic tumor microenvironment (TME). Here, a microalgae-integrated living hydrogel (ACG gel) developed to concurrently enhance hypoxia-constrained starvation therapy and immunotherapy. ACG gel formed in situ following intratumoral injection biohybrid fluid composed alginate, Chlorella sorokiniana, glucose oxidase, facilitated crossing-linking between divalent ions within alginate. microalgae sorokiniana embedded generate abundant oxygen through photosynthesis, enhancing oxidase-catalyzed consumption shifting TME from immunosuppressive immunopermissive status, thus reducing cell energy supply boosting antitumor immunity. In murine 4T1 models, significantly suppresses growth effectively prevents postoperative recurrence. This study, leveraging as natural oxygenerators, provides versatile universal strategy development oxygen-dependent therapies.

Язык: Английский

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Ultrasound-triggered and glycosylation inhibition-enhanced tumor piezocatalytic immunotherapy

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 18, 2024

Nanocatalytic immunotherapy holds excellent potential for future cancer therapy due to its rapid activation of the immune system attack tumor cells. However, a high level N-glycosylation can protect cells, compromising anticancer immunity nanocatalytic immunotherapy. Here, we show 2-deoxyglucose (2-DG) and bismuth ferrite co-loaded gel (DBG) scaffold enhanced piezocatalytic After implantation in tumor, DBG generates both reactive oxygen species (ROS) piezoelectric signals when excited with ultrasound irradiation, significantly promoting immunity. Meanwhile, 2-DG released from ROS-sensitive disrupts N-glycans synthesis, further overcoming immunosuppressive microenvironment tumors. The synergy effects ultrasound-triggered glycosylation inhibition are demonstrated on four mouse models. A "hot" tumor-immunity niche is produced inhibit progress lung metastasis elicit strong memory effects. This work provides promising malignant solid tumors featuring low immunogenicity levels N-glycosylation.

Язык: Английский

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