Titanium dioxide nanostructure-loaded Adriamycin surmounts resistance in breast cancer therapy: ABCA/P53/C-myc crosstalk.

ABSTRACT

Aim: To clarify the alternation of gene expression responsible for resistance of Adriamycin (ADR) in rats, in addition to investigation of a novel promising drug-delivery system using titanium dioxide nanoparticles loaded with ADR (TiO2-ADR). Method: Breast cancer was induced in female Sprague-Dawley rats, followed by treatment with ADR (5 mg/kg) or TiO2-ADR (2 mg/kg) for 1 month. Results: Significant improvements in both zinc and calcium levels were observed with TiO2-ADR treatment. Gene expression of ATP-binding cassette transporter membrane proteins (ABCA1 & ABCG1), P53 and Jak-2 showed a significant reduction and overexpression of the C-myc in breast cancer-induced rats. TiO2-ADR demonstrated a notable ability to upregulate these genes. Conclusion: TiO2-ADR could be a promising drug-delivery system for breast cancer therapy.

The current study aimed to investigate a novel and promising drug-delivery system to overcome the resistance problem by loading Adriamycin (ADR) into titanium dioxide nanoparticles (TiO2). The study also aimed to clarify the changes in gene expression responsible for the development of ADR resistance, in a rat model. First, animals were divided into four groups of ten each. Breast cancer was induced in female Sprague-Dawley rats by administering two doses of DMBA (50 and 25 mg/kg), followed by treatment with ADR at a dose of 5 mg/kg for 1 month, or TiO2-ADR at a dose of 2 mg/kg for 1 month. Biochemical and molecular analyses were conducted. Zinc and calcium levels were found to significantly decrease after cancer induction. Treatment with ADR alone or in combination with TiO2 showed a significant improvement in both mineral levels, with the TiO2-ADR group showing superior results. Gene expression of ATP-binding cassette transporter membrane proteins (ABCA1 & ABCG1), P53 and Jak-2 showed a significant decrease after DMBA-induced breast cancer. However, both the ADR- and TiO2-ADR-treated groups showed a notable increase in gene expression, with the TiO2-ADR group showing the highest increase. On the other hand, there was a significant overexpression of the C-myc gene after DMBA-induced breast cancer. However, both ADR and TiO2-ADR treatments resulted in a notable decrease in C-myc gene expression. Based on the data, TiO2-ADR could be a promising drug-delivery system for breast cancer therapy.