Efficacy and hepatotoxicity of tamoxifen-loaded fructose-based nanodrug for breast cancer treatment

Abstract

Breast cancer is one of the most harmful diseases affecting human health. Low drug accumulation at the tumor site and the severe side effects of traditional chemotherapeutics compromise their effectiveness in breast cancer treatment. Utilizing nanocarriers for targeted delivery and controlled release of therapeutics to cancer cells could be a promising pathway to alleviate these problems. Herein, we synthesized a novel prodrug conjugate coupling hydrophilic fructooligosaccharide with hydrophobic tamoxifen via a reactive oxygen species (ROS)-responsive aryl boronic ester linker, these amphiphilic conjugates could self-assemble into nanoparticles with high drug loading capacity and realize not only active breast cancer targeting via fructooligosaccharide moiety, but also controlled drug release through boronic ester bond breakage in higher ROS levels of the tumor cells. These nanoparticles showed specific cellular internalization and targeted cytotoxicity in MCF-7 breast cancer cells. To evaluate the hepatotoxicity of nanodrugs, a liver organoid model was established to simulate the in vivo metabolism of nanodrugs and assess their activities in the liver tissue. The results demonstrated that a low concentration (25 μg mL⁻¹) of nanodrugs could inhibit cellular proliferation of breast cancer cells significantly without showing obvious toxicity to liver organoids, implicating a favorable efficacy and safety profile of these nanodrugs. Therefore, the tamoxifen-loaded fructose-based nanodrug might be a promising platform for improving tumor targeting and reducing side effects in breast cancer treatment.