Targeted and Intrinsic Activity of HA-Functionalized PEI-Nanoceria as a Nano Reactor in Potential Triple-Negative Breast Cancer Treatment

Abstract

Although there has been considerable achievement in the field of breast cancer therapeutics, tackling the disturbing issue of highly potent triple-negative breast cancer (TNBC) still remains a hurdle in cancer therapeutics. Here, for the first time we propose a poly(ethylenimine) (PEI)-mediated approach for the synthesis of hyaluronic acid (HA) tagged cerium oxide nanoparticles (CePEI-NPs) as a therapeutic agent in TNBC. Primarily, the formulated HA-CePEI-NPs upon treatment displayed superior anticancer effect by exhibiting the loss of mitochondrial membrane potential (MMP). These particles acted as a nano reactor by the generation of reactive oxygen species (ROS) during the treatment. We further evaluated the caspase activity which divulgated the activation of caspases-3 and -9 while there was a decrease in the level of Bcl-2. The treatment also resulted in the release of cytochrome c (Cyt c), and in addition, features such as pynknosis and G2/M phase arrest were also noted. Hence the nano reactor property of nano ceria in activating mitochondrial-mediated intrinsic apoptosis highlights its promising role as a nano drug for therapeutic applications in TNBC.