Enhanced Anti-tumor Efficacy of S3I-201 in Breast Cancer Mouse Model Through Wharton Jelly- Exosome

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2024 Sep 18

PMID 39294673

Authors

Masoomeh Hosseini

Rana Ezzeddini

Seyed Mahmoud Hashemi

Sara Soudi

Amir Salek Farrokhi

Affiliations

Soon will be listed here.

Abstract

Objective: Exosomes, membrane-enveloped vesicles found in various cell types, including Wharton's jelly mesenchymal stem cells, play a crucial role in intercellular communication and regulation. Their use as a cell-free nanotechnology and drug delivery system has attracted attention. Triple-negative breast cancer (TNBC) is a major global health problem and is characterized by a high mortality rate. This study investigates the potential of Wharton's Jelly mesenchymal stem cell-derived exosomes (WJ-Exo) as carriers of S3I-201 and their effects on STAT3 expression in breast cancer cell lines, and evaluates whether these exosomes can enhance the anti-tumor effect of S3I-201.

Methods: The filtered WJ-Exos were analyzed by Transmission Electron Microscopy (TEM), Scanning electron microscopy (SEM), Dynamic Light Scattering (DLS), flow cytometry, and Western blotting. These exosomes were then used for loading with S3I-201, resulting in the nano-formulation WJ-Exo(S3I-201). The effect of WJ-Exo(S3I-201) on 4T1 cancer cells was investigated in vitro using MTT assay, flow cytometry, wound healing assay, Western blotting and Quantitative Real-Time Polymerase chain reaction (qPCR) analysis. Finally, the therapeutic efficacy of the nano-formulation was investigated in vivo using a tumor-bearing mouse model.

Results: In vitro experiments showed that co-incubation of 4T1 cells with the nano-formulation resulted in a significant reduction in p-STAT3 levels, induction of apoptosis, modulation of Bcl-2, Bax and caspase-3 protein and gene expression, and inhibition of migration. In vivo, treatment of tumor-bearing mice with WJ-Exo(S3I-201) showed a strong antitumor effect that exceeded the efficacy observed in the S3I-201 group.

Conclusion: Our results demonstrate that WJ-Exo is an effective carrier for targeting S3I-201 to tumor cells and enhances the therapeutic efficacy of S3I-201 in tumor-bearing mice.

Citing Articles

Mesenchymal Stem-Cell-Derived Exosomes as Novel Drug Carriers in Anti-Cancer Treatment: A Myth or Reality?.

Harrell C, Volarevic A, Djonov V, Volarevic V Cells. 2025; 14(3).

PMID: 39936993 PMC: 11817634. DOI: 10.3390/cells14030202.

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