Research Progress of Endoplasmic Reticulum Targeting Metal Complexes in Cancer Therapy DOI

Shihang Xu,

Xiaoling Wu,

Jia Zhu

et al.

Drug Development Research, Journal Year: 2024, Volume and Issue: 85(8)

Published: Dec. 1, 2024

ABSTRACT The development of anticancer drugs that target different organelles has received extensive attention due to the characteristics cancer recurrence, metastasis, and drug resistance. endoplasmic reticulum (ER) is an important structure within cell primarily responsible for protein synthesis, folding, modification, transport plays a crucial role in function health. ER stress activation induces apoptosis. New with mechanisms selectivity can be designed because redox activity, composition diversity, metal complexes regulation. Over past few decades, dozens have killed cells through stress, showing powerful tumor‐suppressive effects. This review summarizes progress research on metallic induce over years, which expected bring more breakthroughs field medicine life science.

Language: Английский

Designing a Mitochondria-Targeted Theranostic Cyclometalated Iridium(III) Complex: Overcoming Cisplatin Resistance and Inhibiting Tumor Metastasis through Necroptosis and Immune Response DOI
Wenjuan Li, Ting Li, Ying Pan

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(5), P. 3843 - 3859

Published: March 5, 2024

To develop a potential theranostic metal agent to reverse the resistance of cancer cells cisplatin and effectively inhibit tumor growth metastasis, we proposed design cyclometalated iridium (Ir) complex based on properties environment (TME). end, designed synthesized series Ir(III) 2-hydroxy-1-naphthaldehyde thiosemicarbazone complexes by modifying hydrogen atom(s) N-3 position compounds structure dimers then investigated their structure–activity structure–fluorescence relationships obtain an (Ir5) with remarkable fluorescence cytotoxicity cells. Ir5 not only possesses mitochondria-targeted but also overcomes inhibits metastasis in vivo. Besides, confirmed anticancer mechanisms acting different components TME: directly killing liver inducing necroptosis activating necroptosis-related immune response.

Language: Английский

Citations

20
Developing a Copper(II) Isopropyl 2-Pyridyl Ketone Thiosemicarbazone Compound Based on the IB Subdomain of Human Serum Albumin–Indomethacin Complex: Inhibiting Tumor Growth by Remodeling the Tumor Microenvironment DOI
Xueyu Man, Shanhe Li, Gang Xu

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(7), P. 5744 - 5757

Published: March 29, 2024

To develop a next-generation metal agent and dual-agent multitargeted combination therapy, we developed copper (Cu) compound based on the properties of human serum albumin (HSA)–indomethacin (IND) complex to remodel tumor microenvironment (TME). We optimized series Cu(II) isopropyl 2-pyridyl ketone thiosemicarbazone compounds obtain (C4) with significant cytotoxicity then constructed an HSA–IND–C4 (HSA–IND–C4) delivery system. IND C4 bind hydrophobic cavities IB IIA domains HSA, respectively. In vivo, not only showed enhanced antitumor efficacy relative + but also improved their targeting ability decreased side effects. The mechanism involved acting different components TME. inhibited tumor-related inflammation, while induced apoptosis autophagy cancer cells angiogenesis.

Language: Английский

Citations

16
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

23
Novel Pt(IV) complex OAP2 induces STING activation and pyroptosis via mitochondrial membrane remodeling for synergistic chemo-immunotherapy DOI Creative Commons

Renming Fan,

Ruizhuo Lin,

Shuo Zhang

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2023, Volume and Issue: 14(4), P. 1742 - 1758

Published: Dec. 16, 2023

Mitochondrial membrane remodeling can trigger the release of mitochondrial DNA (mtDNA), leading to activation cellular oxidative stress and immune responses. While role in promoting inflammation hepatocytes is well-established, its effects on tumors have remained unclear. In this study, we designed a novel Pt(IV) complex, OAP2, which composed oxaliplatin (Oxa) acetaminophen (APAP), enhance anti-tumor amplify response. Our findings demonstrate that OAP2 induces nuclear damage, resulting production DNA. Additionally, downregulates expression Sam50, promote mtDNA secretion, double-stranded accumulation ultimately synergistically activating intracellular cGAS-STING pathway. The induced by overcomes limitations Oxa STING pathway simultaneously promotes gasdermin-D-mediated cell pyroptosis. also dendritic maturation enhances quantity efficacy cytotoxic T cells, thereby inhibiting cancer proliferation metastasis. Briefly, our study introduces first small-molecule inhibitor regulates for active immunotherapy research, may provide creative idea targeting organelle therapy.

Language: Английский

Citations

23
Designing an anticancer Pd(II) complex as poly(ADP-ribose) polymerase 1 inhibitor DOI

Shuangshuang Gai,

Peng Cao,

Xuwei Zhong

et al.

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 297, P. 139885 - 139885

Published: Jan. 14, 2025

Language: Английский

Citations

1
H-ferritin-nanocaged gadolinium nanoparticles for ultra-sensitive MR molecular imaging DOI Creative Commons
Jianlin Zhang, Yuan Chang, Lingfei Kong

et al.

Theranostics, Journal Year: 2024, Volume and Issue: 14(5), P. 1956 - 1965

Published: Jan. 1, 2024

Rationale: Magnetic resonance imaging (MRI) is a powerful diagnostic technology by providing high-resolution imaging.Although MRI sufficiently valued in its resolving morphology, it has poor sensitivity for tracking biomarkers.Therefore, contrast agents are often used to improve sensitivity.However, the clinically Gd chelates limited improving owing their low relaxivity.The objective of this study develop novel agent achieve highly sensitive biomarkers vivo.Methods: A Gd-based nanoprobe composed gadolinium nanoparticle encapsulated within human H-ferritin nanocage (Gd-HFn) been developed.The specificity and Gd-HFn were evaluated vivo tumor-bearing mice apolipoprotein E-deficient (Apoe -/ -) MRI.Results: The probe shows extremely high relaxivity values (r1 = 549 s -1 mM , r2 1555 under 1.5-T magnetic field; r1 428 1286 3.0-T field), which 175-fold higher than that standard Dotarem (Gd-DOTA, =3.13 ) field, 150-fold field.Owing substantially enhanced values, achieved tumor targeting receptor TfR1 enabled visualization tumors approaching angiogenic switch.Conclusions: developed makes more tool simultaneously functional morphological information, paves way new perspective molecular imaging.

Language: Английский

Citations

8
Bioactive metal-based nanomedicines for boosting anti-tumor immunity: Advance, challenge, and perspective DOI
Zifan Pei,

Longxiao Li,

Nailin Yang

et al.

Coordination Chemistry Reviews, Journal Year: 2024, Volume and Issue: 517, P. 215969 - 215969

Published: June 10, 2024

Language: Английский

Citations

7
Targeted Nanotheranostics: Integration of Preclinical MRI and CT in the Molecular Imaging and Therapy of Advanced Diseases DOI Creative Commons

Jyoti Bonlawar,

Aseem Setia,

Ranadheer Reddy Challa

et al.

Nanotheranostics, Journal Year: 2024, Volume and Issue: 8(3), P. 401 - 426

Published: Jan. 1, 2024

The integration of preclinical magnetic resonance imaging (MRI) and computed tomography (CT) methods has significantly enhanced the area therapy targeted nanomedicine.Nanotheranostics, which make use nanoparticles, are a significant advancement in MRI CT imaging.In addition to giving high-resolution anatomical features functional information simultaneously, these multifunctional agents improve contrast when used.In enabling early disease detection, precise localization, personalised monitoring, they also enable detection.Fusion enables vivo tracking drug-loaded nanoparticles.MRI, provides real-time monitoring nanoparticle distribution, accumulation, release at cellular tissue levels, can be used assess efficacy drug delivery systems.The localization nanoparticles within body is achievable through imaging.This technique enhances capabilities by providing information.CT allows for quantitative measurements concentration, essential evaluating pharmacokinetics biodistribution nanomedicine.In this article, we emphasize into molecular advanced diseases.

Language: Английский

Citations

5
A novel Au(III) agent designed to inhibit tumor growth and metastasis through inducing immunogenic cell death DOI
Wenjuan Li, Shanhe Li, Xueyu Man

et al.

Rare Metals, Journal Year: 2024, Volume and Issue: unknown

Published: July 22, 2024

Language: Английский

Citations

4
Developing a Rhodium(III) Complex to Reprogram the Tumor Immune and Metabolic Microenvironments: Overcoming Multidrug Resistance and Metastasis in Non-Small Cell Lung Cancer DOI
Wenjuan Li, Shanhe Li,

Minghui Zhu

et al.

Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 67(19), P. 17243 - 17258

Published: Sept. 19, 2024

To effectively inhibit the growth and metastasis of non-small cell lung cancer (NSCLC) overcome its multidrug resistance (MDR), we designed synthesized a series rhodium (Rh, III) 2-benzoylpyridine thiosemicarbazone complexes. Through studying their structure-activity relationships, identified Rh(III) complex (Rh4) with excellent cytotoxicity against multidrug-resistant cells (A549/ADR cells). Additionally, successfully constructed an apoferritin (AFt) nanoparticle (NP) delivery system (AFt-Rh4 NPs). Importantly, AFt-Rh4 NPs not only exhibited antitumor antimetastatic capabilities NSCLC

Language: Английский

Citations

4