Background Gastric cancer treatment faces numerous challenges, and despite
medical advancements, it remains one of the leading causes of cancer-related
mortality worldwide. One of the primary challenges in treating this disease is drug
resistance, where lncRNA molecules, such as HOTAIR, play a significant role.
Therefore, inhibiting lncRNAs using RNA interference (RNAi) and employing
natural bioactive compounds like quercetin could be an effective approach to gastric
cancer treatment. However, there is a need for carriers to deliver these molecules
specifically to cancer cells. In this study, Fe3O4 magnetic nanoparticles were used
as targeted carriers for the delivery of quercetin and a gene encoding shRNA against
HOTAIR (shDNA).
Aim: The aim of this study was to synthesize Fe3O4 nanoparticles coated with
dextran as carriers for quercetin and shDNA HOTAIR and to evaluate their effects
on AGS gastric cancer cell lines.
Methodology: Fe3O4 nanoparticles were synthesized using the co-precipitation
method and coated with DEAE-DEXTRAN. Quercetin was loaded onto the
nanoparticles. Characterization of the nanoparticles was performed using XRD,
FTIR, FESEM, HR-TEM, and VSM analyses. Subsequently, the shDNA HOTAIR
genetic construct was prepared via PCR and loaded onto the nanoparticles. To
assess the biological effects of the synthesized nanocomposite, MTT, scratch,
apoptosis, and real-time PCR assays were conducted.
Findings: The results of this study demonstrated that the nanocomposite carrying
quercetin and shDNA HOTAIR reduced the proliferation, viability, and migration
of AGS cells. Additionally, this nanocomposite significantly induced apoptosis in
AGS cells (P < 0.05). Moreover, the expression of lncRNA HOTAIR in treated
cells was reduced, indicating the effective impact of the nanocomposite in
downregulating this gene's activity.
Conclusions: The findings of this study suggest that the use of Fe3O4 magnetic
nanoparticles as targeted carriers for quercetin and shDNA HO