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Silibinin‐Loaded Nanoparticles for Drug Delivery in Gastric Cancer: In Vitro Modulating miR‐181a and miR‐34a to Inhibit Cancer Cell Growth and Migration

Mohsen Karami Fath,Parastoo Vakilinezami,Zohre Abdoli Keleshtery,Zahra Sima Azgomi,Sharareh Nezamivand Chegini,M. Shahriarinour,Saman Seyfizadeh Saraabestani,Mahzad Diyarkojouri,M. Nikpassand,N. Ranji

Published 2025 in Food Science & Nutrition

ABSTRACT

ABSTRACT Silibinin (C25H22O10), a notable bioactive flavonolignans, is recognized for its anticancer properties. However, due to its poor water solubility, the objective of this study was to design and synthesize nanocarriers to enhance the solubility of silibinin for effective delivery to AGS gastric cancer cells. This study details the synthesis of PEG400‐OA nanoparticles for silibinin delivery to AGS cells. Various physicochemical techniques, including FT‐IR, TGA, EDX, FE‐SEM, and TEM, were employed to characterize the silibinin‐loaded nanoparticles (SLNs), confirming particle size, elemental composition, thermal stability, and paramagnetic properties. The anticancer effects of the SLNs were assessed using MTT assay, scratch test, and Q‐RT‐PCR. The SLNs exhibited particle sizes ranging from 45 to 60 nm, with thermal stability below 110°C. TEM images suggested a micelles/liposomes structure due to the low polydispersity and spherical shape of the particles. EDX analysis revealed the presence of C, O, N, and P, confirming the incorporation of phospholipids (micelle/liposome) within the SLNs. The IC50 of SLNs in AGS cells was determined to be 28.21 μg/mL. Antimigration effects of SLNs's were demonstrated through the downregulation of miR‐181a and upregulation of its potential targets (TGFB, SMAD3, and β‐catenin genes), as well as the upregulation of miR‐34a and downregulation of its potential target (E‐Cadherin antimigration gene). The findings suggest that nanoparticles serve as effective nanocarriers for the targeted delivery of silibinin to cancer cells. Silibinin‐loaded micelles/liposomes nanoparticles (SLNs) appear to inhibit cancer cell proliferation and migration by modulating the expressionof miRNAs and their target mRNAs.

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