Poly (I:C)- and doxorubicin-loaded magnetic dendrimeric nanoparticles affect the apoptosis-related gene expressions in MCF-7 cells

Authors: ROUHOLLAH KHODADUST, AKTAN ALPSOY, GÖZDE ÜNSOY, UFUK GÜNDÜZ

Abstract: Use of nanoparticles as drug carrier vectors has great potential to circumvent the limitations associated with chemotherapy, including drug resistance and destructive side effects. For this purpose, magnetic generation 4 dendrimeric nanoparticles were prepared to carry chemotherapeutic agent doxorubicin (G:₄-DOX) and immune modulator polyinosinic:polycytidylic acid [Poly(I:C)]. As previously reported, DOX and Poly(I:C) was loaded onto G₄ nanoparticles (PIC-G₄-DOX). Cellular internalization study using confocal microscopy demonstrated high levels of cellular internalization of PIC-G₄-DOX nanoparticles by MCF-7 cells. This resulted in higher efficacy of PIC-G₄-DOX nanoparticles in killing MCF-7 breast cancer cells. Alteration in the expression levels of selected genes was determined by RT-qPCR analyses. Proapoptotic NOXA, PUMA, and BAX genes were upregulated, and SURVIVIN, APOLLON, and BCL-2 genes were downregulated, indicating the cell-killing effectiveness of PIC-G₄-DOX nanoparticles. Gene expression analysis provided some insights into the possible molecular mechanisms on cytotoxicity of DOX and Poly(I:C) delivered through G₄ magnetic nanoparticles. The results demonstrated that PIC-G₄-DOX can be useful for targeted delivery affecting apoptotic pathways, resulting in an advanced degree of cancer-cell-killing. They are promising for targeting cancer-cells because of their stability, biocompatibility, higher internalization, and toxicity.

Keywords: Targeted drug delivery, magnetic dendrimeric nanoparticles, Poly(I:C), doxorubicin, gene expression

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