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Keywords
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Cobalt ferrite magnetic nanoparticle, lncRNA, Platinum-based drugs, Stomach
cancer, shRNA
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Abstract
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Cisplatin (CDDP) is a common drug for gastric cancer (GC) treatment. The aberrant expression of MALAT-1, a long noncoding RNA, plays a critical role in CDDP resistance. Thus, silencing MALAT-1 using short hairpin RNAs (shRNA) can be an effective way to overcome CDDP resistance. The present study aims to use magnetic cobalt ferrite nanoparticles (CoFe2O4), functionalized with polyethyleneimine and chitosan, as targeted carriers for delivering Pt(IV)-COOH prodrug and shRNA-expressing cassettes to AGS cells. The shRNA-expressing cassettes were synthesized by PCR. Functionalized CoFe₂O₄ nanoparticles were synthesized, and their morphology, structural, and magnetic properties were evaluated using FESEM, EDAX, HRTEM, XRD, FT-IR, VSM and Zeta potential analyzer. The delivery of shRNA to AGS cells was evaluated using fluorescent microscopy. The efficiency of MALAT-1 gene silencing was quantified by qPCR. Additionally, cell viability, migration, and apoptosis induction were assessed using MTT, wound healing, and caspase 3/7 activity assays, respectively. The results showed the zeta potential of + 15.98 mV with PDI of 0.034. The cell uptake efficiency was 89% which led to a 9-fold decrease in MALAT-1 expression. Furthermore, these nanoparticles significantly reduced cell viability and migration while increasing caspase 3/7 activity (p < 0.05). This study demonstrated the efficacy of functionalized cobalt ferrite nanocomplexes for drug and gene therapy in vitro, but this needs to be confirmed in an in vivo study.
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