Development of mesoporous magnetic nanoparticles supported idarubicin and investigation of apoptotic and cytotoxic effects on cancer cell lines

Many methods are used for cancer treatment, especially chemotherapy. In addition to the their therapeutic effects, chemotherapeutic drugs also have serious disadvantages, such as not being cell and tissue-specific, causing toxicity in many tissues, and developing drug resistance. Many methods, especially nanocarriers, have been designed to overcome these disadvantages.

In this study, we synthesized mesoporous silica iron oxide nanoparticles with different pore diameters and loaded idarubicin (6MFe₃O₄-NH₂-IDA and 35MFe₃O₄-NH₂-IDA). The synthesized molecules were characterized using FT-IR, XRD, and SEM methods. The cytotoxic effects of unbound idarubicin and idarubicin-loaded nanoparticles on MCF7 and HL-60 cell lines were examined by MTT test. Additionally, the expression of anti-apoptotic (Survivin and BCL-2) and apoptotic (BAX, PUMA, and NOXA) genes of the nanoparticles were measured by PCR method. As a result of the analyses, it was seen that nanoparticles with the desired properties and sizes were synthesized. In MTT analysis, it was observed that both nanoparticles dramatically decreased the IC₅₀ value in cell lines. However, the 35MFe₃O₄-NH₂-IDA molecule was found to have lower IC₅₀ values. IC₅₀ values ​​for pristine IDA, 6MFe₃O₄-NH₂, and 35MFe₃O₄-NH₂ at 24 h were found to be 3.56, 1.24 and 0.25 µM in the MCF7 cell line and 4.15, 1.16 and 0.34 µM in the HL-60 cell line, respectively. Additionally, apoptotic gene expression increased, and anti-apoptotic gene expression decreased.

Our study demonstrates that the effectiveness of idarubicin can be significantly enhanced by its application with mesoporous nanocarriers. This enhancement is attributed to the controlled release of idarubicin from the nanocarrier, which circumvents drug resistance mechanisms, improves drug solubility, and increases the drug-carrying capacity per unit volume due to the porous structure of the carrier. These findings underscore the potential of the synthesized nanocarrier in cancer treatment and provide a clear direction for future research in this field.