A Mitochondria‐Targeted Photosensitizer for Combined Pyroptosis and Apoptosis with NIR‐II Fluorescence/Photoacoustic Imaging‐Guided Phototherapy DOI
Ben Wang, Hui Zhou, Lu Chen

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 21, 2024

Overcoming tumor apoptosis resistance is a major challenge in enhancing cancer therapy. Pyroptosis, lytic form of programmed cell death (PCD) involving inflammasomes, Gasdermin family proteins, and cysteine proteases, offers potential treatment. While photodynamic therapy (PDT) can induce pyroptosis by generating reactive oxygen species (ROS) through the activation photosensitizers (PSs), many PSs lack specific subcellular targets are limited to first near-infrared window, potentially reducing treatment effectiveness. Therefore, developing effective, deep-penetrating, organelle-targeted pyroptosis-mediated phototherapy essential for strategies. Here, we synthesized four molecules with varying benzene ring numbers thiopyrylium structures preliminarily explore their properties. The near-infrared-II (NIR-II) PS Z1, higher count, exhibited superior ROS generation mitochondria-targeting abilities, large Stokes shift. Through nano-precipitation method, Z1 nanoparticles (NPs) also demonstrated high (especially type-I ROS) upon 808 nm laser irradiation, leading efficient mitochondria dysfunction combined apoptosis. Moreover, they exceptional tumor-targeting ability via NIR-II fluorescence imaging (NIR-II FI) photoacoustic (PAI). Furthermore, NPs-mediated effectively inhibited growth minimal adverse effects. Our findings offer promising strategy therapy, warranting further preclinical investigations PDT.

Language: Английский

Efficient NIR-II Type-I AIE Photosensitizer for Mitochondria-Targeted Photodynamic Therapy through Synergistic Apoptosis–Ferroptosis DOI
Jiabao Zhuang, Bing Wang, Huan Chen

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(10), P. 9110 - 9125

Published: May 5, 2023

Hypoxia, the hallmark of malignant tumors, has been recognized as a major obstacle for photodynamic therapy (PDT). Precisely targeting cancer cells in intricate biological scenarios by hypoxia-resistant photosensitizer (PS) is cornerstone to conquer inevitable tumor recurrence and metastasis. Herein, we describe an organic NIR-II PS (TPEQM-DMA) possessing potent type-I phototherapeutic efficacy overcome intrinsic pitfalls PDT combating hypoxic tumors. TPEQM-DMA exhibited prominent emission (>1000 nm) with aggregation-induced feature efficiently produced superoxide anion hydroxyl radical aggregate state under white light irradiation exclusively through low-O2-dependent photochemical process. The suitable cationic nature assisted accumulate cancerous mitochondria. Meanwhile, impaired cellular redox homeostasis, led mitochondrial dysfunction, raised level lethal peroxidized lipids, which induced apoptosis ferroptosis. This synergistic cell death modality enabled suppress growth cells, multicellular spheroids, To improve pharmacological properties TPEQM-DMA, nanoparticles were prepared encapsulation polymer. In vivo experiments proved appealing fluorescence imaging-guided effect

Language: Английский

Citations

123
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

120
Engineering of BODIPY-based theranostics for cancer therapy DOI
Zhiqiang Mao, Ji Hyeon Kim, Jieun Lee

et al.

Coordination Chemistry Reviews, Journal Year: 2022, Volume and Issue: 476, P. 214908 - 214908

Published: Nov. 7, 2022

Language: Английский

Citations

101
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

92
Doping Engineering to Modulate Lattice and Electronic Structure for Enhanced Piezocatalytic Therapy and Ferroptosis DOI Open Access
Boshi Tian, Ruixue Tian, Shaohua Liu

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(38)

Published: July 12, 2023

Piezocatalytic therapy, which generates reactive oxygen species (ROS) under mechanical force, has garnered extensive attention for its use in cancer therapy owing to deep tissue penetration depth and less O2 -dependence. However, the piezocatalytic therapeutic efficiency is limited poor piezoresponse, low separation of electron-hole pairs, complicated tumor microenvironment (TME). Herein, a biodegradable, porous Mn-doped ZnO (Mn-ZnO) nanocluster with enhanced piezoelectric effect constructed via doping engineering. Mn-doping not only induces lattice distortion increase polarization but also creates rich vacancies (OV ) suppressing recombination leading high-efficiency generation ROS ultrasound irradiation. Moreover, shows TME-responsive multienzyme-mimicking activity glutathione (GSH) depletion ability mixed valence Mn (II/III), further aggravating oxidative stress. Density functional theory calculations show that can improve performance enzyme Mn-ZnO due presence OV . Benefiting from boosting GSH ability, significantly accelerate accumulation lipid peroxide inactivate peroxidase 4 (GPX4) induce ferroptosis. The work may provide new guidance exploring novel sonosensitizers therapy.

Language: Английский

Citations

85
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

84
Engineered Metallacycle‐Based Supramolecular Photosensitizers for Effective Photodynamic Therapy DOI

Le Tuan Tu,

Chonglu Li,

Xiaoxing Xiong

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(15)

Published: Feb. 14, 2023

Abstract Although metallacycle‐based supramolecular photosensitizers (PSs) have attracted increasing attention in biomedicine, their clinical translation is still hindered by inherent dark toxicity. Herein, we report what to our knowledge the first example of a molecular engineering approach building blocks metallacycles for constructing series PSs ( RuA–RuD ), with aim simultaneously reducing toxicity and enhancing phototoxicity, consequently obtaining high phototoxicity indexes (PI). Detailed vitro investigations demonstrate that display cancer cellular uptake remarkable antitumor activity even under hypoxic conditions. Notably, RuD exhibited no displayed highest PI value (≈406). Theoretical calculations verified has largest steric hindrance lowest singlet‐triplet energy gap (Δ E ST , 0.61 eV). Further vivo studies confirmed allows safe effective phototherapy against A549 tumors.

Language: Английский

Citations

77
A review on metal complexes and its anti-cancer activities: Recent updates from in vivo studies DOI Open Access
Suman Adhikari, Priyatosh Nath, Alakesh Das

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 171, P. 116211 - 116211

Published: Jan. 29, 2024

Research into cancer therapeutics has uncovered various potential medications based on metal-containing scaffolds after the discovery and clinical applications of cisplatin as an anti-cancer agent. This resulted in many metallodrugs that can be put medical applications. These have a wider variety functions mechanisms action than pure organic molecules. Although platinum-based medicines are very efficient agents, they often accompanied by significant side effects toxicity limited resistance. Some most studied developed alternatives to include ruthenium, gold, copper, iridium, osmium, which showed effectiveness against cell lines. metal-based represent exciting new category treatments sparked renewed interest search for effective therapies. Despite widespread development metal complexes touted powerful promising vitro therapeutics, only small percentage these compounds shown their worth vivo models. Metallodrugs, more less toxic drugs treat drug-resistant cells, focus this review. Here, we highlighted some recently Pt, Ru, Au, Cu, Ir, Os antitumor properties between 2017 2023.

Language: Английский

Citations

66
Exosome camouflaged coordination-assembled Iridium(III) photosensitizers for apoptosis-autophagy-ferroptosis induced combination therapy against melanoma DOI
Tao Feng, Zixin Tang, Johannes Karges

et al.

Biomaterials, Journal Year: 2023, Volume and Issue: 301, P. 122212 - 122212

Published: June 24, 2023

Language: Английский

Citations

46
Acceptor engineering of metallacycles with high phototoxicity indices for safe and effective photodynamic therapy DOI Creative Commons

Chonglu Li,

Le Tu,

Jingfang Yang

et al.

Chemical Science, Journal Year: 2023, Volume and Issue: 14(11), P. 2901 - 2909

Published: Jan. 1, 2023

Although metallacycle-based photosensitizers have attracted increasing attention in biomedicine, their clinical application has been hindered by inherent dark toxicity and unsatisfactory phototherapeutic efficiency. Herein, we employ a π-expansion strategy for ruthenium acceptors to develop series of Ru(ii) metallacycles (Ru1-Ru4), while simultaneously reducing enhancing phototoxicity, thus obtaining high phototoxicity index (PI). These enable deep-tissue (∼7 mm) fluorescence imaging reactive oxygen species (ROS) production exhibit remarkable anti-tumor activity even under hypoxic conditions. Notably, Ru4 the lowest toxicity, highest ROS generation ability an optimal PI (∼146). Theoretical calculations verify that exhibits largest steric bulk singlet-triplet energy gap (ΔEST, 0.62 eV). In vivo studies confirm allows effective safe phototherapy against A549 tumors. This work is expected open new avenue design high-performance metal-based potential applications.

Language: Английский

Citations

43