Application of hesperetin nanoparticles prepared with AEAA-PEG-PCL carrier in breast cancer treatment

Abstract

Breast cancer is the most prevalent cancer among women, and the leading cause of cancer-related deaths worldwide. Current chemotherapy regimens are not highly effective and often accompanied by severe side effects. Hesperetin (HE) is a bioflavonoid extracted from citrus fruits, which exhibits diverse biological activities including prominent anti-tumor effects. However, its poor water solubility and low stability lead to limited bioavailability upon oral administration and high susceptibility to renal clearance, thereby restricting its clinical application. To improve the bioavailability of HE, we formulated it into nanoparticles and evaluated its in vitro anti-breast cancer efficacy. Specifically, aminoethyl-anisamide amphiphilic polymer polyethylene glycol-poly(ε-caprolactone) (AEAA-PEG-PCL), a carrier with active targeting properties, was employed to encapsulate HE via a nanoprecipitation method, yielding HE nanoparticles (NPs) with small size, uniform particle size distribution, and spherical morphology. These HE NPs achieve sustained release of HE in a simulated tumor microenvironment. Further in vitro cancer cell culture studies were conducted. Compared with unmodified nanoparticles, this targeted delivery system exhibited enhanced tumor cell internalization and significantly inhibited tumor cell proliferation, which indicates its considerable potential in improving breast cancer treatment efficacy. Therefore, HE NPs represent a promising drug delivery platform for breast cancer.