Membrane-anchoring clickable Iridium(III) nanosonosensitizer in situ evokes PANoptosis for augmented tumor sono-immunotherapy

Nano Today, Journal Year: 2024, Volume and Issue: 56, P. 102270 - 102270

Published: April 15, 2024

Language: Английский

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A Cyclometalated Ruthenium(II) Complex Induces Oncosis for Synergistic Activation of Innate and Adaptive Immunity

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(31)

Published: May 21, 2024

Abstract An optimal cancer chemotherapy regimen should effectively address the drug resistance of tumors while eliciting antitumor‐immune responses. Research has shown that non‐apoptotic cell death, such as pyroptosis and ferroptosis, can enhance immune response. Despite this, there been limited investigation reporting on mechanisms oncosis its correlation with Herein, we designed synthesized a Ru(II) complex targeted nucleus mitochondria to induce oncosis. Briefly, disrupts DNA, which active polyADP‐ribose polymerase 1, accompanied by ATP consumption porimin activation. Concurrently, mitochondrial damage endoplasmic reticulum stress result in release Ca 2+ ions increased expression Calpain 1. Subsequently, specific pore proteins 1 promote cristae destruction or vacuolation, ultimately leading membrane rupture. The analysis RNA sequencing demonstrates initiate oncosis‐associated pathway activate both innate adaptive immunity. In vivo experiments have confirmed promotes dendritic maturation awakens cytotoxic T lymphocytes but also activates inducing polarization macrophages towards an M1 phenotype.

Language: Английский

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How does ferrocene correlate with ferroptosis? Multiple approaches to explore ferrocene-appended GPX4 inhibitors as anticancer agents

Chemical Science, Journal Year: 2024, Volume and Issue: 15(27), P. 10477 - 10490

Published: Jan. 1, 2024

Ferroptosis has emerged as a form of programmed cell death and exhibits remarkable promise for anticancer therapy. However, it is challenging to discover ferroptosis inducers with new chemotypes high ferroptosis-inducing potency. Herein, we report series ferrocenyl-appended GPX4 inhibitors rationally designed in "one stone kills two birds" strategy. selectivity assays, inhibitory activity CETSA experiments validated the inhibition novel compounds on GPX4. In particular, ROS-related bioactivity assays highlighted ROS-inducing ability 17 at molecular level their enhancement cellular level. These data confirmed dual role ferrocene both bioisostere motif maintaining capacity certain molecules also ROS producer enhance vulnerability cancer cells, thereby attenuating tumor growth

Language: Английский

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Leveraging Tumor Microenvironment to Boost Synergistic Photodynamic Therapy, Ferroptosis Anti‐Tumor Efficiency Based on a Functional Iridium(III) Complex

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Abstract The tumor microenvironment (TME) severely limits the efficacy of clinical applications photodynamic therapy (PDT). development a functional agent allowing full use TME to boost synergistic PDT and ferroptosis anti‐tumor efficiency is an appealing yet significantly challenging task. Herein, overcome adverse influence on hypoxia high level glutathione (GSH) in TME, imine bond introduced into Ir(III)‐ferrocene complex construct small molecule drug, named Ir‐Fc, for tumors’ imaging therapy. cleavage lysosome effectively disrupts photoinduced electron transfer (PET) process, realizing decomposition Ir‐Fc Fc‐CHO Ir‐NH 2 . produces •OH by Fenton reactions under dark conditions induces cells, shows prominent performance type‐I type‐II reactive oxygen species (ROS) production. Meanwhile, pathway simultaneously consumes large amounts GSH O relieving hypoxia. These distinctive outputs make exceptional effective This study thus brings new revolutionary protocol practical cancer treatment.

Language: Английский

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Quasi Fe MIL-53 nanozyme inducing ferroptosis and immunogenic cell death for cancer immunotherapy

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 7, 2025

Nanozymes offer diverse therapeutic potentials for cancer treatment which is dependent on the development of nanomaterials. Quasi-metal-organic framework a class metal-organic framework-derived nanomaterials with transition state from frameworks towards metal oxide featuring porous structure and high activity. Herein an iron-based quasi-metal-organic nanozyme Q-MIL-53(Fe) reported via controlled deligandation strategy, exhibiting enhanced peroxidase-/catalase-mimic activity glutathione depletion capacity, whose underlying mechanisms are studied density functional theory calculations. demonstrates biocompatibility superior antitumor efficacy compared to pristine MIL-53(Fe). It can activate immune response by inducing ferroptosis immunogenic cell death, promoting dendritic maturation T lymphocytes infiltration. Furthermore, combination programmed death protein 1 antibody amplifies immunotherapy. This study validates its immunotherapy induction potential. would broaden application open avenues developing nanozymes. treatment. In this work, authors report quasi-metal organic peroxidase catalase-mimicking capacity use it tumor death.

Language: Английский

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Natural products targeting macroautophagy signaling in hepatocellular carcinoma therapy: Recent evidence and perspectives

Phytotherapy Research, Journal Year: 2024, Volume and Issue: 38(3), P. 1623 - 1650

Published: Feb. 1, 2024

Abstract Hepatocellular carcinoma (HCC), presently the second leading cause of global cancer‐related mortality, continues to pose significant challenges in realm medical oncology, impacting both clinical drug selection and mechanistic research. Recent investigations have unveiled autophagy‐related signaling as a promising avenue for HCC treatment. A growing body research has highlighted pivotal role autophagy‐modulating natural products inhibiting progression. In this context, we provide concise overview fundamental autophagy mechanism delineate involvement autophagic pathways development. Additionally, review pertinent studies demonstrating how regulate mitigate HCC. Our findings indicate that exhibit cytotoxic effects through induction excessive autophagy, simultaneously impeding cell proliferation by inhibition, thereby depriving cells essential energy. These been associated with various pathways, including PI3K/AKT, MAPK, AMPK, Wnt/β‐catenin, Beclin‐1, ferroautophagy. results underscore considerable therapeutic potential However, it is important note present study did not establish definitive thresholds or inhibition products. Further domain imperative gain comprehensive insights into dual equipping us better understanding double‐edged sword management.

Language: Английский

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Ferroptosis Inducing Co(III) Polypyridine Sulfasalazine Complex for Therapeutically Enhanced Anticancer Therapy

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(48)

Published: Aug. 13, 2024

Abstract Despite significant improvements in the treatment of cancerous tumors last decades, cancer remains one deadliest diseases worldwide. To overcome shortcomings currently applied chemotherapeutic treatments, much research efforts have been devoted towards development ferroptosis inducing anticancer agents. Ferroptosis is a newly described form regulated, non‐apoptotic cell death that associated with high potential inside clinics. Herein, chemical synthesis and biological evaluation Co(III) polypyridine sulfasalazine complex as inducer reported. Upon entering cells, metal primarily accumulated mitochondria, triggering production hydroxy radicals lipid peroxides, ultimately causing by ferroptosis. The compound demonstrated to eradicate various monolayer cells well colon carcinoma multicellular tumor spheroids. best our knowledge this study reports on first example capable

Language: Английский

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Iridium(III) Photosensitizers Induce Simultaneous Pyroptosis and Ferroptosis for Multi‐Network Synergistic Tumor Immunotherapy

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(49)

Published: Aug. 24, 2024

Abstract The integration of pyroptosis and ferroptosis hybrid cell death induction to augment immune activation represents a promising avenue for anti‐tumor treatment, but there is lack research. Herein, we developed two iridium (III)‐triphenylamine photosensitizers, IrC IrF , with the capacity disrupt redox balance induce photo‐driven cascade damage DNA Kelch‐like ECH‐associated protein 1 (KEAP1). absent in melanoma 2 (AIM2)‐related cytoplasmic nucleic acid‐sensing pathway, triggered by damaged DNA, leads gasdermin D (GSDMD)‐mediated pyroptosis. Simultaneously, iron homeostasis, regulated KEAP1/nuclear factor erythroid 2‐related (NRF2)/heme oxygenase (HO‐1) serves as pivotal bridge, facilitating not only E (GSDME)‐mediated non‐canonical pyroptosis, also synergy glutathione peroxidase 4 (GPX4) depletion. collaborative action generates synergistic effect that elicits immunogenic death, stimulates robust response effectively inhibits tumor growth vivo. Our work introduces first metal‐based small molecule dual‐inducers potent cancer immunotherapy, highlights significance homeostasis vital hub connecting effects ferroptosis.

Language: Английский

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Modulation of Metal Homeostasis for Cancer Therapy

ChemPlusChem, Journal Year: 2024, Volume and Issue: 89(6)

Published: Feb. 7, 2024

Metal ions such as iron, zinc, copper, manganese, and calcium are essential for normal cellular processes, including DNA synthesis, enzyme activity, signaling, oxidative stress regulation. When the balance of metal homeostasis is disrupted, it can lead to various pathological conditions, cancer. Thus, understanding role in cancer has led development anti-tumor strategies that specifically target imbalance. Up now, diverse small molecule-based chelators, ionophores, complexes, metal-based nanomaterials have been developed restore metals or exploit dysregulation therapeutic purposes. They hold great promise inhibiting tumor growth, preventing metastasis, enhancing effectiveness existing therapies. In this review, we aim provide a comprehensive summary employed modulate therapy. Their modulation mechanisms succinctly described, their recent applications field therapy discussed. At end, limitations these approaches addressed, potential avenues future developments explored.

Language: Английский

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Mitochondria‐targeting metallodrugs for cancer therapy: perspectives from cell death modes

ChemMedChem, Journal Year: 2024, Volume and Issue: 19(15)

Published: May 2, 2024

Abstract Mitochondria, recognized as the cellular powerhouses, are indispensable organelles responsible for crucial processes, such energy metabolism, material synthesis, and signaling transduction. Their intricate involvement in a broad spectrum of diseases, particularly cancer, has propelled exploration mitochondria‐targeting treatment promising strategy cancer therapy. Since groundbreaking discovery cisplatin, trajectory research on development metal complexes have been marked by continuous advancement, giving rise to diverse array metallodrugs characterized variations ligand types, center properties, oxidation states. By specifically targeting mitochondria, these exhibit remarkable ability elicit various programmed cell death pathways, encompassing apoptosis, autophagy, ferroptosis. This review primarily focuses recent developments transition metal‐based agents, offering comprehensive their capacity induce distinct modes. The aim is not only disseminate knowledge but also stimulate an active field toward new clinical applications novel anticancer mechanisms.

Language: Английский

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