Synthesis of multifunctional nano-drug with targeted delivery for the synergistic pathway of various inducers on inhibition of breast cancer cell line

Abstract

Abstract Background and objective: In recent years, interest has grown in the anti-cancer properties of natural compounds, particularly polyphenols including, Oleuropein, Quercetin, Coumarin (an aromatase inhibitor) and Valproic acid, with fewer side effects. Oleuropein stops the cell cycle in the G2/M phase by inhibiting metalloproteinase and increasing the expression of some caspases. Quercetin induces apoptosis by reducing the activity of the PI3K/Akt/IKK-/NF-B pathway. Valproic acid is an inhibitor of histone deacetylases which has a vital role in preventing the spread and progression of cancer. However, the therapeutic effects of polyphenols have constrained by their poor bioavailability. The goal of this study was creation of a natural magnetic nano-complex that is more bioavailable to examine how oleuropein, quercetin, coumarin, and valproic acid work in concert to limit cell growth. Methods: In this work, a silicon bridge (sio-N-) was built using nano-magnetic iron and methoxy silane to create a magnetic nano-complex with four plant-derived substances: oleuropein, coumarin, quercetin, and valproic acid. These complexes were then analyzed using a variety of spectroscopic and size measures. Then, using the MTT technique and real-time PCR, the inhibitory impact and expression of apoptotic genes on the MCF7 cell line was assessed. Results: FT-IR, SEM, TEM, EDX, XRD, DLS, and VSM techniques used to validate the synthesis of the nano-complex. The magnetic nano-complex exhibits a greater level of toxicity than the quadruple compound without nanoparticles, according to the MTT test findings. Moreover, compared to any of the materials or their combinations, the magnetic quadruple nanocomposite dramatically reduced the inhibition of cancer cells. Hoechst staining and flow cytometry cell techniques used to confirm this assumption. The quadruple combination and quadruple nanocomposite of magnetism induced overexpression of p53, bim, and bak and reduced BCL2 expression, according to real-time PCR data. Thus, our results showed that the nano-complex treatment increased the expression level of genes involved in apoptosis by up to two times. Conclusion: Using plant-derived materials with various properties attached to magnetic nanoparticles can increase their toxicity against breast cancer cells and increase their concentration in the cell. Additionally, by creating a synergistic effect through various molecular pathways, it inhibits the proliferation of cancer cells and causes them to undergo apoptosis.