Shikonin induces the apoptosis and pyroptosis of EGFR-T790M-mutant drug-resistant non-small cell lung cancer cells via the degradation of cyclooxygenase-2 DOI Creative Commons
Shiyu Cao, H. Li,

Xiaoyan Ye

et al.

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: Dec. 20, 2024

The T790M mutation in the epidermal growth factor receptor (EGFR) gene is primary cause of resistance to EGFR-tyrosine kinase inhibitor (TKI) therapy non-small cell lung cancer (NSCLC) patients. Previous research demonstrated that certain traditional Chinese medicine (TCM) monomers exhibit anti-tumor effects against various malignancies. This study aims investigate potentials shikonin screened from a TCM monomer library containing 1060 killing EGFR-T790M drug-resistant NSCLC cells and elucidate underlying mechanisms. MTT method was used screen for with significant on H1975 carrying mutation. influences identified were determined by colony formation assay. Annexin-V/PI staining JC-1 applied detect apoptosis. membrane integrity detected lactate dehydrogenase (LDH) release Reactive oxygen species (ROS) generation analyzed using DCFH-DA as probe. mechanisms affecting stability cyclooxygenase-2 (COX-2) evaluated specific inhibitors protein degradation pathways. Western blotting performed assess alteration COX-2 expression or enzymatic activity related signal pathways well apoptotic pyroptotic markers. Shikonin potent cytotoxic compound EGFR-T790M-mutant cells. induced apoptosis pyroptosis triggering activation caspase cascade cleavage poly (ADP-ribose) polymerase gasdermin E elevating intracellular ROS levels. Further investigations revealed via proteasome pathway, thereby decreasing level subsequently inhibiting downstream PDK1/Akt Erk1/2 signaling through induction production. Notably, overexpression attenuated shikonin-induced pyroptosis, whereas inhibition celecoxib enhanced shikonin. Combination treatment may be suitable therapeutic strategy treatment.

Language: Английский

A Dihydroartemisinin‐Loaded Nanoreactor Motivates Anti‐Cancer Immunotherapy by Synergy‐Induced Ferroptosis to Activate Cgas/STING for Reprogramming of Macrophage DOI

Liu‐Gen Li,

Xiaoxin Yang,

Hua‐Zhen Xu

et al.

Advanced Healthcare Materials, Journal Year: 2023, Volume and Issue: 12(28)

Published: Aug. 11, 2023

Infiltration of tumor-associated macrophages (TAM) characterized by an M2 phenotype is overriding feature in malignant tumors. Reprogramming TAM the most cutting-edge strategy for cancer therapy. In present study, iron-based metal-organic framework (MOF) nanoreactor loaded with dihydroartemisinin (DHA) developed, which provides high uptake and retains their viability, thus effectively addressing inefficiency DHA at low concentrations. Impressively, DHA@MIL-101 can selectively accumulate tumor tissues remodel to M1 phenotype. The results RNA sequencing further suggest that this may regulate ferroptosis, a DNA damage signaling pathway TAM. Indeed, outcomes confirm triggers ferroptosis addition, findings reveal induced nanoreactors activates intracellular cGAS sensor, resulting binding STING IRF3 thereby up-regulating immunogenicity. contrast, blocking impairs DHA@MIL-101-induced activation phenotypic remodeling. Finally, it shown deploy anti-tumor immunotherapy through ferroptosis-mediated reprogramming. Taken together, immune efficacy achieved TAM's remodeling delivering iron ions into using nanoreactors, providing novel approach combining phytopharmaceuticals nanocarriers microenvironment.

Language: Английский

Citations

28
A Cancer Nanovaccine Based on an FeAl-Layered Double Hydroxide Framework for Reactive Oxygen Species-Augmented Metalloimmunotherapy DOI
Mengyu Chang, Man Wang, Bin Liu

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(11), P. 8143 - 8156

Published: March 4, 2024

The complexity and heterogeneity of individual tumors have hindered the efficacy existing therapeutic cancer vaccines, sparking intensive interest in development more effective situ vaccines. Herein, we introduce a nanovaccine for reactive oxygen species-augmented metalloimmunotherapy which FeAl-layered double hydroxide (LDH) is used as delivery vehicle with dihydroartemisinin (DHA) cargo. LDH framework acid-labile can be degraded tumor microenvironment, releasing iron ions, aluminum DHA. ions contribute to aggravated intratumoral oxidative stress injury by synergistic Fenton reaction DHA activation, causing apoptosis, ferroptosis, immunogenic cell death cells. subsequently released tumor-associated antigens adjuvant form generate robust long-term immune responses against recurrence metastasis. Moreover, Fe ion-enabled T1-weighted magnetic resonance imaging facilitate real-time therapy monitoring. This cancer-nanovaccine-mediated strategy has potential revolutionizing precision immunotherapy landscape.

Language: Английский

Citations

10
A pH and glutathione-responsive carbon monoxide-driven nano-herb delivery system for enhanced immunotherapy in colorectal cancer DOI
Yang Chen, Hui Ming, Bowen Li

et al.

Journal of Controlled Release, Journal Year: 2024, Volume and Issue: 376, P. 659 - 677

Published: Oct. 28, 2024

Language: Английский

Citations

9
Synthesis, characterization, and toxicity assessments of Silymarin-loaded Ni-Fe Metal-organic frameworks: Evidence from in vitro and in vivo evaluations DOI
Fatemeh Rahimi,

Sheida Shahraki,

Mohammad Reza Hajinezhad

et al.

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: 92, P. 105372 - 105372

Published: Jan. 21, 2024

Language: Английский

Citations

5
Determining M2 macrophages content for the anti-tumor effects of metal-organic framework-encapsulated pazopanib nanoparticles in breast cancer DOI Creative Commons
Zhijie Xu, Zhiyang Zhou, Xiaoxin Yang

et al.

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: July 20, 2024

Abstract Pazopanib (PAZ), an oral multi-tyrosine kinase inhibitor, demonstrates promising cytostatic activities against various human cancers. However, its clinical utility is limited by substantial side effects and therapeutic resistance. We developed a nanoplatform capable of delivering PAZ for enhanced anti-breast cancer therapy. Nanometer-sized PAZ@Fe-MOF, compared to free PAZ, demonstrated increased anti-tumor in both syngeneic murine 4T1 xenograft MDA-MB-231 breast models. High-throughput single-cell RNA sequencing (scRNAseq) revealed that PAZ@Fe-MOF significantly reduced pro-tumorigenic M2-like macrophage populations at tumor sites suppressed M2-type signaling pathways, such as ATF6-TGFBR1-SMAD3, well chemokines including CCL17, CCL22, CCL24. reprogramed the inhibitory immune microenvironment curbed tumorigenicity blocking polarization M2 phenotype macrophages. This platform offers new strategy improving cytotoxicity It provides method evaluate immunological response cells PAZ-mediated treatment.

Language: Английский

Citations

5
Acidic Environment-Responsive Metal Organic Framework-Mediated Dihydroartemisinin Delivery for Triggering Production of Reactive Oxygen Species in Drug-Resistant Lung Cancer DOI Creative Commons
Xiaojie Yan, Xueying Zhao, Mingde Fan

et al.

International Journal of Nanomedicine, Journal Year: 2024, Volume and Issue: Volume 19, P. 3847 - 3859

Published: April 1, 2024

Background: Dihydroartemisinin (DHA) has emerged as a promising candidate for anticancer therapy. However, the application of DHA in clinics been hampered by several limitations including poor bioavailability, short circulation life, and low solubility, significantly restricting its therapeutic efficacy leading to notable side effects during treatment. Purpose: We present DHA-loaded zeolitic imidazolate framework-8 (D-ZIF) with controllable targeted release properties, enhanced antitumor while reducing potential effects. Methods: D-ZIF was prepared one-pot synthesis method using methylimidazole (MIM), Zn(NO 3 ) 2 • 6H O DHA. characterized physical chemical properties TEM, DLS, XRD, FT-IR, TG. measured drug loading efficiency cumulative different pH conditions. evaluated cytotoxicity on renal cell carcinoma (RCC786-O), glioma cells (U251), TAX-resistant human lung adenocarcinoma (A549-TAX) CCK8 vitro. explored possible mechanism Western blot. biocompatibility hemolysis vivo mice model TUNEL testing blood biomarker evaluations. Results: showed rhombic dodecahedral morphology size 129± 7.2 nm possessed noticeable encapsulation (72.9%). After 48 hours, released 70.0% loaded at 6.5, only 42.1% 7.4. The pH-triggered programmed behavior could enhance effect minimizing under normal physiological Compared free group 31.75% A549-TAX apoptosis, percentage apoptotic approximately 76.67% group. inhibited tumor growth inducing apoptosis through ROS production regulation Nrf2/HO-1 P38 MAPK signaling pathways. potent treating tumors high safety vivo. Conclusion: This pH-responsive targeting towards cells, thereby increasing concentration sites negligible Herein, holds great promise curing cancers minimal adverse Keywords: MOF, delivery, controlled release, cancer therapy

Language: Английский

Citations

4
Nanozyme-Based Strategies in Cancer Immunotherapy: Overcoming Resistance to Enhance Therapeutic Efficacy DOI Creative Commons
Guangjian Hou, Yukun Xu, Chunhua Wang

et al.

Aging and Disease, Journal Year: 2025, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2025

Nanozymes, which are nanomaterials that replicate the catalytic activities of natural enzymes in biological systems, have recently demonstrated considerable potential improving cancer immunotherapy by altering tumor microenvironment. Nanozyme-driven immune responses represent an innovative therapeutic modality with high effectiveness and minimal side effects. These nanozymes activate system to specifically recognize destroy cells. Combined immunotherapeutic agents, can amplify anti-cancer integrating remodeling immunogenic cell death (ICD). This review offers a thorough discussion about various involved immunity, including those mimicking catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), oxidase (OXD). It also discusses challenges future directions for translating nanozyme platforms into clinical applications, enhancing susceptibility cells immunotherapy. Nanozyme-based strategies substantial oncology, offering new effective options management.

Language: Английский

Citations

0
Prominent Supramolecular Systems for Cancer Therapy: From Structural Design to Tailored Applications DOI
Jiawei Zhang, Qingya Zhang,

LI Xiao-jia

et al.

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 117754 - 117754

Published: May 1, 2025

Language: Английский

Citations

0
Current status of controlled onco-therapies based on metal organic frameworks DOI Creative Commons

Yixuan Yang,

Xiaofeng Dai

RSC Advances, Journal Year: 2024, Volume and Issue: 14(18), P. 12817 - 12828

Published: Jan. 1, 2024

Most MOFs for controllable cancer treatment act as drug delivery vehicle and/or anti-cancer agent. Molecules with roles such chemotherapies, gases, peptides or nucleic acids can be loaded into that decompose in cells the TME to release its cargoes.

Language: Английский

Citations

3
Effects and mechanisms of N6-methyladenosine RNA methylation in environmental pollutant-induced carcinogenesis DOI Creative Commons
Tong‐Fei Li, Zhijie Xu, Kui Zhang

et al.

Ecotoxicology and Environmental Safety, Journal Year: 2024, Volume and Issue: 277, P. 116372 - 116372

Published: April 25, 2024

Environmental pollution, including air plastic contamination, and heavy metal exposure, is a pressing global issue. This crisis contributes significantly to pollution-related diseases critical risk factor for chronic health conditions, cancer. Mounting evidence underscores the pivotal role of N6-methyladenosine (m

Language: Английский

Citations

3