Poly (I:C)- and doxorubicin-loaded magnetic dendrimeric nanoparticles affect the apoptosis-related gene expressions...

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 (G₄-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.