Integration of AIEgens into covalent organic frameworks for pyroptosis and ferroptosis primed cancer immunotherapy

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Сен. 2, 2023

Immunogenic programmed cell death, such as pyroptosis and ferroptosis, efficiently induces an acute inflammatory response boosts antitumor immunity. However, the exploration of dual-inducers, particularly nonmetallic inducers, capable triggering both ferroptosis remains limited. Here we show construction a covalent organic framework (COF-919) from planar twisted AIEgen-based motifs dual-inducer for efficient Mechanistic studies reveal that COF-919 displays stronger near-infrared light absorption, lower band energy, longer lifetime to favor generation reactive oxygen species (ROS) photothermal conversion, pyroptosis. Because its good ROS production capability, it upregulates intracellular lipid peroxidation, leading glutathione depletion, low expression peroxidase 4, induction ferroptosis. Additionally, by effectively inhibits tumor metastasis recurrence, resulting in over 90% growth inhibition cure rates exceeding 80%.

Язык: Английский

---

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

---

An acid-responsive MOF nanomedicine for augmented anti-tumor immunotherapy via a metal ion interference-mediated pyroptotic pathway

Biomaterials, Год журнала: 2023, Номер 302, С. 122333 - 122333

Опубликована: Сен. 16, 2023

Язык: Английский

---

Deep Insight of Design, Mechanism, and Cancer Theranostic Strategy of Nanozymes

Nano-Micro Letters, Год журнала: 2023, Номер 16(1)

Опубликована: Ноя. 21, 2023

Since the discovery of enzyme-like activity Fe

Язык: Английский

---

Ablation of Gap Junction Protein Improves the Efficiency of Nanozyme‐Mediated Catalytic/Starvation/Mild‐Temperature Photothermal Therapy

Advanced Materials, Год журнала: 2023, Номер 35(22)

Опубликована: Март 25, 2023

Reactive oxygen species (ROS)-mediated tumor catalytic therapy is typically hindered by gap junction proteins that form cell-to-cell channels to remove cytotoxic ROS, thereby protecting cells from oxidative damage. In this work, a multifunctional nanozyme, FePGOGA, designed and prepared Fe(III)-mediated polymerization (FeP), followed glucose oxidase (GOx) GAP19 peptides co-loading through electrostatic π-π interactions. The FePGOGA nanozyme exhibits excellent cascade peroxidase- glutathione-oxidase-like activities efficiently catalyze hydrogen peroxide conversion hydroxyl radicals convert reduced glutathione oxidized disulfide. loaded GOx starves the tumors aggravates stress decomposition, while block hemichannels inducing degradation of Cx43, thus increasing accumulation intracellular decreasing transport glucose. Furthermore, ROS reacts with primary amines heat shock destroy their structure function, enabling photothermal at widely sought-after mild temperature (mildPTT, ≤45 °C). vivo experiments demonstrate significant antitumor effectof on cal27 xenograft under near-infrared light irradiation. This study demonstrates successful ablation overcome resistance ROS-mediated therapy, providing regulator suppress self-preservation during starvation, mildPTT.

Язык: Английский

---

Extracellular Vesicles‐Derived Hybrid Nanoplatforms for Amplified CD47 Blockade‐Based Cancer Immunotherapy

Advanced Materials, Год журнала: 2023, Номер 35(35)

Опубликована: Июнь 29, 2023

Immunomodulation of tumor-associated macrophages (TAMs) into tumor-inhibiting M1-like phenotype is a promising but challenging strategy. Cleverly, tumor cells overexpress CD47, "don't eat me" signal that ligates with the regulatory protein alpha (SIRPα) on to escape phagocytosis. Thus, effective re-education TAMs "eat type and blocking CD47-SIRPα signaling play pivotal roles in immunotherapy. Herein, it reported hybrid nanovesicles (hEL-RS17) derived from extracellular vesicles M1 decorated RS17 peptide, an antitumor peptide specifically binds CD47 blocks signaling, can actively target remodel TAM phenotypes. Consequently, more infiltrate tissue phagocytize due blockade. By further co-encapsulating chemotherapeutic agent shikonin, photosensitizer IR820, immunomodulator polymetformin hEL-RS17, enhanced effect obtained combinational treatment modality close synergy among each component. Upon laser irradiation, designed SPI@hEL-RS17 nanoparticles exert potent efficacy against both 4T1 breast B16F10 melanoma models, which not only suppresses primary growth also inhibits lung metastasis prevents recurrence, exhibiting great potential boosting blockade-based

Язык: Английский

---

Bioorthogonal Disruption of Pyroptosis Checkpoint for High-Efficiency Pyroptosis Cancer Therapy

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(30), С. 16658 - 16668

Опубликована: Июль 24, 2023

Pyroptosis is an inflammatory form of programmed cell death that holds great promise in cancer therapy. However, autophagy as the crucial pyroptosis checkpoint and self-protective mechanism cells significantly weakens therapeutic efficiency. Here, a bioorthogonal nanoregulator constructed to induce disrupt checkpoint, enabling high-efficiency The allows situ synthesis accumulation photosensitizer PpIX mitochondria directly produce mitochondrial ROS, thus triggering pyroptosis. Meanwhile, generated inhibitor via palladium-catalyzed chemistry can boost efficacy. With biomimetic membrane coating, this platform for modulating presents specificity poses no harm normal tissue, resulting highly efficient safe antitumor treatment. To our knowledge, first report on disrupting intrinsic protective tumor This work highlights plays key regulative role therapy, which would motivate future design regimens.

Язык: Английский

---

Transition-Metal-Based Nanozymes: Synthesis, Mechanisms of Therapeutic Action, and Applications in Cancer Treatment

ACS Nano, Год журнала: 2024, Номер 18(19), С. 12049 - 12095

Опубликована: Май 2, 2024

Cancer, as one of the leading causes death worldwide, drives advancement cutting-edge technologies for cancer treatment. Transition-metal-based nanozymes emerge promising therapeutic nanodrugs that provide a reference therapy. In this review, we present recent breakthrough First, comprehensively outline preparation strategies involved in creating transition-metal-based nanozymes, including hydrothermal method, solvothermal chemical reduction biomimetic mineralization and sol–gel method. Subsequently, elucidate catalytic mechanisms (catalase (CAT)-like activities), peroxidase (POD)-like oxidase (OXD)-like activities) superoxide dismutase (SOD)-like along with their activity regulation such morphology control, size manipulation, modulation, composition adjustment surface modification under environmental stimulation. Furthermore, elaborate on diverse applications anticancer therapies encompassing radiotherapy (RT), chemodynamic therapy (CDT), photodynamic (PDT), photothermal (PTT), sonodynamic (SDT), immunotherapy, synergistic Finally, challenges faced by are discussed alongside future research directions. The purpose review is to offer scientific guidance will enhance clinical based transition metals.

Язык: Английский

---

Hydrogen Sulfide Gas Amplified ROS Cascade: FeS@GOx Hybrid Nanozyme Designed for Boosting Tumor Chemodynamic Immunotherapy

Advanced Healthcare Materials, Год журнала: 2023, Номер 12(23)

Опубликована: Апрель 11, 2023

Chemodynamic immunotherapy that utilizes catalysts to produce reactive oxygen species (ROS) for killing tumor cells and arousing antitumor immunity has received considerable attention. However, it is still restricted by low ROS production efficiency insufficient immune activation, due intricate redox homeostasis in the microenvironment (TME). Herein, a metalloprotein-like hybrid nanozyme (FeS@GOx) designed situ growth of (ferrous sulfide, FeS) natural enzyme (glucose oxidase, GOx) amplify cascade boosting chemodynamic immunotherapy. In FeS@GOx, GOx allows conversion endogenous glucose gluconic acid hydrogen peroxide, which provides favorable increasing peroxide subsequent Fenton reaction FeS nanozymes, thus reinforcing production. Notably, sulfide (H2 S) release activated generation-related pH decrease, can suppress activity thioredoxin reductase catalase further inhibit elimination. Thus, FeS@GOx sustainably accumulation perturb intracellular improve therapy trigger robust immunogenic cell death effective combined with checkpoint blockade. This work proposes feasible H2 S amplified strategy employing bioinspired nanozyme, providing novel pathway multi-enzyme-mediated TME modulation precise efficient

Язык: Английский

---

A Mild Hyperthermia Hollow Carbon Nanozyme as Pyroptosis Inducer for Boosted Antitumor Immunity

ACS Nano, Год журнала: 2023, Номер 17(22), С. 22844 - 22858

Опубликована: Ноя. 9, 2023

The immune checkpoint blockade (ICB) antibody immunotherapy has demonstrated clinical benefits for multiple cancers. However, the efficacy of in tumors is suppressed by deficient tumor immunogenicity and immunosuppressive microenvironments. Pyroptosis, a form programmed cell death, can release antigens, activate effective immunogenicity, improve efficiency ICB, but efficient pyroptosis treatment currently limited. Herein, we show mild hyperthermia-enhanced pyroptosis-mediated based on hollow carbon nanozyme, which specifically amplify oxidative stress-triggered synchronously magnify anticancer responses microenvironment. sphere modified with iron copper atoms (HCS-FeCu) enzyme-mimicking activities been engineered to induce via radical oxygen species (ROS)-Tom20-Bax-Caspase 3-gasdermin E (GSDME) signaling pathway under light activation. Both vitro vivo antineoplastic results confirm superiority HCS-FeCu nanozyme-induced pyroptosis. Moreover, photothermal-activated combining anti-PD-1 enhance antitumor immunotherapy. Theoretical calculations further indicate that photothermal stimulation generates high-energy electrons enhances interaction between surface adsorbed oxygen, facilitating molecular activation, improves ROS production efficiency. This work presents an approach effectively transforms immunologically "cold" into "hot" ones, significant implications

Язык: Английский

---