Co-delivery of anticancer drugs and biologics can provide synergetic effects and outperform single delivery therapies. Here, a nanoparticle (NP) system for co-delivery of methotrexate (MTX) and STAT3 siRNA has been developed and tested . Mesoporous silica nanoparticles (MSNs) were functionalized with chitosan (ch) by covalent grafting mediated by aminopropyl triethoxysilane (APTES) via glutaraldehyde as the linker. Co-delivery of MTX and STAT3 siRNA to MCF7 cells was demonstrated in cells by flow cytometric analysis and confocal laser scanning fluorescence microscopy for use in breast cancer treatment. MTX either competitively inhibits the dihydrofolate reductase (DHFR) receptor or suppresses the STAT3 metabolic pathway. STAT3 protein plays an essential role in cell division, proliferation and survival. Reduction of the protein by both MTX and STAT3 siRNA, achieved by chMSNs, significantly decreased the viability of breast cancer cells compared to single treatments alone. Cellular uptake of modified NPs was increased over time when additional free MTX was added implicating the DHFR receptor in uptake. In addition, protein corona compositions coated the NPs outer surface, were different between the NPs with and without drug potentially modulating cellular uptake. This study is the first report on co-delivery of MTX and STAT3 siRNA by chitosan modified MSNs.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1080/21691401.2022.2030746 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Regulatory mechanisms of haptoglobin on particulate matter-induced epithelial-to-mesenchymal transition in bronchial epithelial cells.
J Thorac Dis
December 2024
Key Laboratory of Interventional Pulmonology of Zhejiang Province, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Background: It has been proposed that repeated exposure of bronchial epithelial cells to atmospheric particulate matter (PM) could disrupt airway epithelial integrity and lead to epithelial-to-mesenchymal transition (EMT) and ultimately airway remodeling. The molecular mechanisms underlying PM-related bronchial epithelial EMT have not yet been elucidated. The aim of this research is to clarify the molecular mechanism of EMT upon PM exposure.
View Article and Find Full Text PDFTREM2 alleviates sepsis-induced acute lung injury by attenuating ferroptosis via the SHP1/STAT3 pathway.
Free Radic Biol Med
January 2025
Department of Anesthesiology, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China; Key Laboratory for Basic Science and Prevention of Perioperative Organ Disfunction, Guangxi Medical University Cancer Hospital, Nanning 530021, Guangxi Zhuang Autonomous Region, China. Electronic address:
Sepsis-induced acute lung injury (ALI) is a complex and life-threatening condition characterized by excessive inflammatory responses, ferroptosis, and oxidative stress. A comprehensive investigation and effective therapeutic strategies are crucial for managing this condition. In this study, we established in vivo sepsis models using lipopolysaccharide (LPS) in wild-type (WT) mice and triggering receptor expressed on myeloid cells 2 (TREM2) knockout (TREM2-KO) mice to assess lung morphology, oxidative stress, and ferroptosis.
View Article and Find Full Text PDFIGF2BP3 Triggers STAT3 Pathway by Stabilizing SRC RNA in an m6A-Dependent Manner to Promote Lymphatic Metastasis in LUAD.
Cancer Sci
January 2025
Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Lymph node metastasis significantly affects the NSCLC patients' staging, treatment strategy, and prognosis. Studies have shown that IGF2BP3, an oncofetal protein and an m6A reader, overexpresses and correlates to lymph node metastasis and worse overall survival in histopathological studies including NSCLC, but its mechanism needs further study. This study explored IGF2BP3's function and mechanism in LUAD lymphatic metastasis using public databases, a human LUAD tissue microarray, human LUAD cells, and a lymphatic metastasis model in male BALB/c nude mice.
View Article and Find Full Text PDFPotential role of signal transducer and activator of transcription 3 in the amygdala in mitigating stress-induced high blood pressure via exercise in rats.
Acta Physiol (Oxf)
February 2025
Department of Physiology, Graduate School of Health and Sports Science, Juntendo University, Chiba, Japan.
Aim: Chronic stress elevates blood pressure, whereas regular exercise exerts antistress and antihypertensive effects. However, the mechanisms of stress-induced hypertension and preventive effects through exercise remain unknown. Thus, we investigated the molecular basis involved in autonomic blood pressure regulation within the amygdala.
View Article and Find Full Text PDFDefining Mechanistic Links Between the Non-Coding Variant rs17673553 in and Lupus Susceptibility.
Int J Mol Sci
January 2025
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by widespread inflammation and autoantibody production. Its development and progression involve genetic, epigenetic, and environmental factors. Although genome-wide association studies (GWAS) have repeatedly identified a susceptibility signal at 16p13, its fine-scale source and its functional and mechanistic role in SLE remain unclear.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!