Effect of Ultra-Low Concentrations of Doxorubicin in Biological Nanoparticles in Breast Tumor Models

Abstract

To date, chemotherapeutic agents remain the primary method for treating many oncological diseases, including breast cancer (BC). However, numerous side effects caused by the indiscriminate destruction of actively dividing cells limit the safe use of chemotherapeutic agents in clinical practice. Due to the combination of unique properties of nanoparticles, including high biocompatibility and the ability to overcome biological barriers, biological nanoparticles (BNP) are a promising tool for reducing the unwanted toxicity of modern chemotherapeutic agents. This study examined the efficacy of delivering ultra-low concentrations of doxorubicin (0.0544 mg/kg), a dose that is 100 times less than the single therapeutic dose used in a mouse model, using orthotopic and functionalized exosome-like nanoparticles in BC models in vitro and in vivo. It was shown that doxorubicin loaded in BNP exhibited increased cytotoxic activity compared to the free chemotherapeutic agent in vitro. Moreover, a more pronounced activity of functionalized (targeted) nanoparticles towards breast cancer cell receptors was demonstrated compared to orthotopic particles obtained from the tumor. In an in vivo experiment on mice with BC, doxorubicin in ultra-low doses incorporated in BNP did not show an anti-tumor effect; however, there was a trend towards a reduction in tumor nodule size with the administration of orthotopic and functionalized BNP with doxorubicin. Therefore, (1) BNP enhance anti-tumor activity, allowing for a reduced dose of the administered chemotherapeutic agent, (2) the creation of targeted nanoparticles ensures enhanced accumulation of the drug in tumor cells, but (3) ultra-low doses of the chemotherapeutic agent do not have a pronounced effect on BC growth in vivo. The results of the study indicate the potential for using BNP as a strategy to reduce off-target toxicity of modern chemotherapeutic agents.