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

Yinzhen Pan,

Zhijun Zhang

et al.

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

Immunogenic Cell Death Inducing Metal Complexes for Cancer Therapy DOI Creative Commons
Lingpu Zhang, Nicolás Montesdeoca, Johannes Karges

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(21)

Published: Feb. 21, 2023

Cancer is one of the deadliest diseases worldwide. Recent statistics have shown that metastases and tumor relapse are leading causes cancer-associated deaths. While traditional treatments able to efficiently remove primary tumor, secondary tumors remain poorly accessible. Capitalizing on this there an urgent need for novel treatment modalities. Among most promising approaches, increasing research interest has been devoted immunogenic cell death inducing agents trigger localized cancer cells as well induce immune response inside whole organism. Preliminary studies compounds could be overcome metastatic relapsing tumors. Herein, application metal complexes systematically reviewed.

Language: Английский

Citations

127
Near-infrared metal agents assisting precision medicine: from strategic design to bioimaging and therapeutic applications DOI

Chonglu Li,

Yida Pang,

Yuling Xu

et al.

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(13), P. 4392 - 4442

Published: Jan. 1, 2023

Metal agents have made incredible strides in preclinical research and clinical applications, but their short emission/absorption wavelengths continue to be a barrier distribution, therapeutic action, visual tracking, efficacy evaluation.

Language: Английский

Citations

93
Metal-Based Photosensitizers as Inducers of Regulated Cell Death Mechanisms DOI
Yiyi Zhang, Bich‐Thuy Doan, Gilles Gasser

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(16), P. 10135 - 10155

Published: Aug. 3, 2023

Over the last few decades, various forms of regulated cell death (RCD) have been discovered and were found to improve cancer treatment. Although there are several reviews on RCD induced by photodynamic therapy (PDT), a comprehensive summary covering metal-based photosensitizers (PSs) as inducers has not yet presented. In this review, we systematically summarize works PSs that induce different types RCD, including ferroptosis, immunogenic (ICD), pyroptosis. The characteristics mechanisms each explained. At end section, reported commonalities between inducing same is emphasized, future perspectives novel discussed at review. Considering essential roles in therapy, hope review will provide stage for advances inducers.

Language: Английский

Citations

92
The crosstalk of CD8+ T cells and ferroptosis in cancer DOI Creative Commons
Zhengjun Lin,

Songzhu Zou,

Kunming Wen

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 15, 2024

Ferroptosis is an iron-dependent, novel form of programmed cell death characterized by lipid peroxidation and glutathione depletion widespread in a variety diseases. CD8+ T cells are the most important effector cytotoxic cells, capable specifically recognizing killing cancer cells. Traditionally, thought to induce mainly through perforin granzyme, Fas-L/Fas binding. In recent years, cell-derived IFN-γ was found promote ferroptosis multiple mechanisms, including upregulation IRF1 IRF8, downregulation system XC-, while shown enhance anti-tumor effects heating tumor immune microenvironment exposure release tumor-associated specific antigens, which results positive feedback pathway. Unfortunately, intra-tumoral more sensitive than limits application inducers cancer. addition, susceptible being regulated other TME, such as macrophages, dendritic Treg, bone marrow-derived immunosuppressive Together, these factors build complex network Therefore, we aim integrate relevant studies reveal potential mechanisms crosstalk between ferroptosis, summarize preclinical models therapy find new therapeutic strategies this review.

Language: Английский

Citations

28
Advances in the Design of Photoactivatable Metallodrugs: Excited State Metallomics DOI Creative Commons
Huayun Shi, Rafael C. Marchi, Peter J. Sadler

et al.

Angewandte Chemie International Edition, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 13, 2025

Abstract Photoactivatable metal complexes offer the prospect of novel drugs with low side effects and new mechanisms action to combat resistance current therapy. We highlight recent progress in design platinum, ruthenium, iridium, gold other transition complexes, especially for applications as anticancer anti‐infective agents. In particular, understanding excited state chemistry related identification bioactive species (excited metallomics/pharmacophores) is important. metallodrugs are classified here photocatalysts, photorelease agents ligand‐activated Their activation wavelengths, cellular action, experimental theoretical metallomics states photoproducts discussed explore strategies investigation photoactivatable metallodrugs. These have potential clinical Photodynamic Therapy (PDT), Photoactivated Chemotherapy (PACT) Photothermal (PTT).

Language: Английский

Citations

4
Evoking Ferroptosis by Synergistic Enhancement of a Cyclopentadienyl Iridium‐Betulin Immune Agonist DOI Open Access

Mengdi Lv,

Yue Zheng,

Jian Wu

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(48)

Published: Oct. 13, 2023

Abstract Ferroptosis is a form of programmed cell death driven by iron‐dependent lipid peroxidation (LPO) with the potential for antitumor immunity activation. In this study, nonferrous cyclopentadienyl metal‐based ferroptosis inducer [Ir(Cp*)(Bet)Cl]Cl ( Ir‐Bet ) was developed metal‐ligand synergistic enhancement (MLSE) strategy involving reaction [Ir(Cp*)Cl] 2 Cl natural product Betulin. The fusion Betulin iridium (Ir‐Cp*) species as not only tremendously enhanced antiproliferative activity toward cancer cells, but also activated ferritinophagy iron homeostasis regulation PI3K/Akt/mTOR cascade inhibition lower dosage Betulin, and then evoked an immune response nuclear factor kappa‐B (NF‐κB) activation Ir‐Cp* species. Further immunogenic (ICD) occurred remarkable through glutathione (GSH) depletion, peroxidase 4 (GPX4) deactivation ferritinophagy. An in vivo vaccination experiment demonstrated desirable effects increasing ratio cytotoxic T cells (CTLs)/regulatory (Tregs).

Language: Английский

Citations

24
Two-photon excitation photosensitizers for photodynamic therapy: From small-molecules to nano-complex systems DOI

Vinayak Juvekar,

Dong Joon Lee, Tae Gwan Park

et al.

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 506, P. 215711 - 215711

Published: Feb. 18, 2024

Language: Английский

Citations

18
Cu(II) complex that synergistically potentiates cytotoxicity and an antitumor immune response by targeting cellular redox homeostasis DOI
Ke-Bin Huang,

Feng-Yang Wang,

Yuan Lu

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(24)

Published: June 4, 2024

Developing anticancer drugs with low side effects is an ongoing challenge. Immunogenic cell death (ICD) has received extensive attention as a potential synergistic modality for cancer immunotherapy. However, only limited set of or treatment modalities can trigger ICD response and none them have cytotoxic selectivity. This provides incentive to explore strategies that might provide more effective inducers free adverse effects. Here, we report metal-based complex ( Cu-1 ) disrupts cellular redox homeostasis effectively stimulates antitumor immune high specificity. Upon entering tumor cells, this Cu(II) enhances the production intracellular radical oxidative species while concurrently depleting glutathione (GSH). As result heightening stress, gives rise relatively cytotoxicity whereas normal cells levels GSH are unaffected. The present initiates potent ferroptosis-dependent inhibits in vivo growth animal model (c57BL/6 mice challenged colorectal cancer). study presents strategy develop could synergistically potentiate selectivity promote apoptosis-independent responses through perturbations homeostasis.

Language: Английский

Citations

15
A Semi‐Automated, High‐Throughput Approach for the Synthesis and Identification of Highly Photo‐Cytotoxic Iridium Complexes DOI Creative Commons
Timothy Kench,

Arielle Rahardjo,

Gianmarco Terrones

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(18)

Published: Feb. 26, 2024

The discovery of new compounds with pharmacological properties is usually a lengthy, laborious and expensive process. Thus, there increasing interest in developing workflows that allow for the rapid synthesis evaluation libraries aim identifying leads further drug development. Herein, we apply combinatorial to build library 90 iridium(III) complexes (81 which are new) over two synthesise-and-test cycles, potential agents photodynamic therapy. We demonstrate power this approach by highly active well-tolerated dark but display very low nM phototoxicity against cancer cells. To detailed structure-activity relationship class have used density functional theory (DFT) calculations determine some key electronic parameters study correlations experimental data. Finally, present an optimised semi-automated protocol obtain multiplex data within 72 hours.

Language: Английский

Citations

14
Recent Advances in Organometallic NIR Iridium(III) Complexes for Detection and Therapy DOI Creative Commons

Shaozhen Jing,

Xiaolei Wu,

Niu Dou

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(1), P. 256 - 256

Published: Jan. 3, 2024

Iridium(III) complexes are emerging as a promising tool in the area of detection and therapy due to their prominent photophysical properties, including higher photostability, tunable phosphorescence emission, long-lasting phosphorescence, high quantum yields. In recent years, much effort has been devoted develop novel near-infrared (NIR) iridium(III) improve signal-to-noise ratio enhance tissue penetration. this review, we summarize different classes organometallic NIR for therapy, cyclometalated ligand-enabled NIR-dye-conjugated complexes. Moreover, prospects challenges targeted discussed.

Language: Английский

Citations

13