Intracellular metal ion-based chemistry for programmed cell death DOI
Y You, Zhongying Guo, Tyler Wolter

et al.

Chemical Society Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Intracellular metal ions play essential roles in multiple physiological processes, including catalytic action, diverse cellular intracellular signaling, and electron transfer. It is crucial to maintain ion homeostasis which achieved by the subtle balance of storage release intracellularly along with influx efflux at interface cell membrane. Dysregulation has been identified as a key mechanism triggering programmed death (PCD). Despite importance initiating PCD, molecular mechanisms within these processes are infrequently discussed. An in-depth understanding review role PCD may better uncover novel tools for cancer diagnosis therapy. Specifically, calcium (Ca

Language: Английский

Organometallic anti-tumor agents: targeting from biomolecules to dynamic bioprocesses DOI
Kun Peng, Yue Zheng, Wei Xia

et al.

Chemical Society Reviews, Journal Year: 2023, Volume and Issue: 52(8), P. 2790 - 2832

Published: Jan. 1, 2023

Organometallics act through specific biomolecular targets or tumor homeostasis perturbation to induce various cell death pathways.

Language: Английский

Citations

93
Cellular zinc metabolism and zinc signaling: from biological functions to diseases and therapeutic targets DOI Creative Commons
Bonan Chen,

Peiyao Yu,

Wai Nok Chan

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Jan. 3, 2024

Abstract Zinc metabolism at the cellular level is critical for many biological processes in body. A key observation disruption of homeostasis, often coinciding with disease progression. As an essential factor maintaining equilibrium, zinc has been increasingly spotlighted context development. Extensive research suggests zinc’s involvement promoting malignancy and invasion cancer cells, despite its low tissue concentration. This led to a growing body literature investigating metabolism, particularly functions transporters storage mechanisms during transportation under control two major transporter families: SLC30 (ZnT) excretion SLC39 (ZIP) intake. Additionally, this element predominantly mediated by metallothioneins (MTs). review consolidates knowledge on signaling underscores potential molecular pathways linking progression, special focus cancer. We also compile summary clinical trials involving ions. Given main localization cell membrane, targeted therapies, including small molecules monoclonal antibodies, offers promising avenues future exploration.

Language: Английский

Citations

88
Tumor Abnormality-Oriented Nanomedicine Design DOI
Quan Zhou, Jiajia Xiang, Nasha Qiu

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(18), P. 10920 - 10989

Published: Sept. 15, 2023

Anticancer nanomedicines have been proven effective in mitigating the side effects of chemotherapeutic drugs. However, challenges remain augmenting their therapeutic efficacy. Nanomedicines responsive to pathological abnormalities tumor microenvironment (TME) are expected overcome biological limitations conventional nanomedicines, enhance efficacies, and further reduce effects. This Review aims quantitate various TME, which may serve as unique endogenous stimuli for design stimuli-responsive provide a broad objective perspective on current understanding cancer treatment. We dissect typical transport process barriers drug delivery, highlight key principles designed tackle series delivery process, discuss "all-into-one" "one-for-all" strategies integrating needed properties nanomedicines. Ultimately, we insight into future perspectives toward clinical translation

Language: Английский

Citations

75
Bioorthogonal Disruption of Pyroptosis Checkpoint for High-Efficiency Pyroptosis Cancer Therapy DOI
Bin Zhang, Zhengwei Liu, Jiawei Zhu

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(30), P. 16658 - 16668

Published: July 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.

Language: Английский

Citations

56
An ultrasound-activatable platinum prodrug for sono-sensitized chemotherapy DOI Creative Commons
Gongyuan Liu, Yachao Zhang, Houzong Yao

et al.

Science Advances, Journal Year: 2023, Volume and Issue: 9(25)

Published: June 21, 2023

Despite the great success achieved by photoactivated chemotherapy, eradicating deep tumors using external sources with high tissue penetration depth remains a challenge. Here, we present cyaninplatin, paradigm of Pt(IV) anticancer prodrug that can be activated ultrasound in precise and spatiotemporally controllable manner. Upon sono-activation, mitochondria-accumulated cyaninplatin exhibits strengthened mitochondrial DNA damage cell killing efficiency, overcomes drug resistance as consequence combined effects from released Pt(II) chemotherapeutics, depletion intracellular reductants, burst reactive oxygen species, which gives rise to therapeutic approach, namely sono-sensitized chemotherapy (SSCT). Guided high-resolution ultrasound, optical, photoacoustic imaging modalities, realizes overall theranostics vivo superior efficacy biosafety. This work highlights practical utility precisely activate prodrugs for eradication tumor lesions broadens biomedical uses Pt coordination complexes.

Language: Английский

Citations

42
Development of Platinum Complexes for Tumor Chemoimmunotherapy DOI
S. Jin, Yan Guo, Xiaoyong Wang

et al.

Chemistry - A European Journal, Journal Year: 2024, Volume and Issue: 30(10)

Published: Jan. 3, 2024

Abstract Platinum complexes are potential antitumor drugs in chemotherapy. Their impact on tumor treatment could be greatly strengthened by combining with immunotherapy. Increasing evidences indicate that the activity of platinum is not limited to chemical killing effects, but also extends immunomodulatory actions. This review introduced general concept chemoimmunotherapy and summarized progress as chemoimmunotherapeutic agents recent years. developed into inducers immunogenic cell death, blockers immune checkpoint, regulators signaling pathway, modulators microenvironment, etc. The synergy between chemotherapeutic effects reinforces complexes, helps them circumvent drug resistance systemic toxicity. exploration for may create new opportunities revive discovery metal anticancer drugs.

Language: Английский

Citations

16
Chemical Design of Magnetic Nanomaterials for Imaging and Ferroptosis-Based Cancer Therapy DOI

Wei Xu,

Guoqiang Guan, Renye Yue

et al.

Chemical Reviews, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Ferroptosis, an iron-dependent form of regulatory cell death, has garnered significant interest as a therapeutic target in cancer treatment due to its distinct characteristics, including lipid peroxide generation and redox imbalance. However, clinical application oncology is currently limited by issues such suboptimal efficacy potential off-target effects. The advent nanotechnology provided new way for overcoming these challenges through the development activatable magnetic nanoparticles (MNPs). These innovative MNPs are designed improve specificity ferroptosis induction. This Review delves into chemical biological principles guiding design ferroptosis-based therapies imaging-guided therapies. It discusses mechanisms attributes ferroptosis, composition MNPs, their mechanism action inducers, integration with advanced imaging techniques monitoring. Additionally, we examine convergence other strategies, chemodynamic therapy, photothermal photodynamic sonodynamic immunotherapy, within context nanomedicine strategies utilizing MNPs. highlights multifunctional surpass limitations conventional treatments, envisioning future drug-resistance-free, precision diagnostics treating recalcitrant cancers.

Language: Английский

Citations

4
Beyond cisplatin: New frontiers in metallodrugs for hard-to-treat triple negative breast cancer DOI
Muhammad Nafees, Muhammad Hanif, Piaoping Yang

et al.

Coordination Chemistry Reviews, Journal Year: 2023, Volume and Issue: 499, P. 215507 - 215507

Published: Oct. 27, 2023

Language: Английский

Citations

25
Developing a Ruthenium(III) Complex to Trigger Gasdermin E-Mediated Pyroptosis and an Immune Response Based on Decitabine and Liposomes: Targeting Inhibition of Gastric Tumor Growth and Metastasis DOI
Wenjuan Li, Shanhe Li, Gang Xu

et al.

Journal of Medicinal Chemistry, Journal Year: 2023, Volume and Issue: 66(18), P. 13072 - 13085

Published: Sept. 13, 2023

To develop next-generation metal drugs with high efficiency and low toxicity for targeting inhibition of gastric tumor growth metastasis, we not only optimized a series ruthenium (Ru, III) 2-hydroxy-1-naphthaldehyde thiosemicarbazone complexes to obtain Ru(III) complex (4b) remarkable cytotoxicity in vitro but also constructed 4b-decitabine (DCT)/liposome (Lip) delivery system (4b-DCT-Lip). The vivo results showed that 4b-DCT-Lip had stronger capacity inhibit metastasis than 4b-DCT addressed the co-delivery problems improved their ability. Furthermore, confirmed mechanism 4b-DCT/4b-DCT-Lip inhibiting tumor. DCT-upregulated gasdermin E (GSDME) was cleaved by 4b-activated caspase-3 afford GSDME-N terminal then aggregated form nonselective pores on cell membrane tumor, thereby inducing pyroptosis pyroptosis-induced immune response.

Language: Английский

Citations

22
Series of Desloratadine Platinum(IV) Hybrids Displaying Potent Antimetastatic Competence by Inhibiting Epithelial–Mesenchymal Transition and Arousing Immune Response DOI
Ming Zhang, Yan Chen, Zhifang Liu

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(3), P. 2031 - 2048

Published: Jan. 17, 2024

Metastasis is the major obstacle to survival of cancer patients. Herein, a series new desloratadine platinum(IV) conjugates with promising antiproliferative and antimetastatic activities were developed evaluated. The candidate complex caused significant DNA damage stimulated mitochondrial apoptosis through Bcl-2/Bax/caspase3 pathway. Then, it suppressed epithelial–mesenchymal transition (EMT) process in tumors effectively NMT-1/HPCAL1 β-catenin signaling. Subsequently, angiogenesis was inhibited downregulation key proteins HIF-1α, VEGFA, MMP-9, CD34. Moreover, antitumor immunity aroused by synergism EMT reversion decrease histamine level; then, macrophage polarization from M2- M1-type increase CD4+ CD8+ T cells triggered simultaneously tumors.

Language: Английский

Citations

14