Abstract
<jats:p>A hard protein corona was engineered onto tannic acid modified magnetic nanoparticles (SAMN@TA), a magnetic and luminescent core-shell nano-carrier, using Bovine Serum Amine Oxidase (BSAO), an enzyme catalysing the oxidation of polyamines and producing the corresponding aldehydes and hydrogen peroxide. The absorption and intracellular bioactivity of the self-assembled multimodal SAMN@TA@BSAO were investigated on an intestinal barrier model built with human colorectal adenocarcinoma (Caco-2) cells. The tailored BSAO corona possessed fouling resistance and, at the same time, was able to activate the clathrin-mediated endocytosis (CME) mechanism. Despite its size and intrinsic complexity, the nano-vehicle was effectively transported across the cell layer, safely transiting across the cell cytoplasm and reaching the lumen. As a function of intracellular polyamine concentration, the system biological activity induced intracellular oxidative stress, leading to the activation of Keap1/Nrf2 oxidative protection pathway. The SAMN@TA@BSAO effect was well described by a dose response curve with an EC50 of around 30 µg mL-1 and a programmable killing efficiency (&gt; 50.0%), recalling the feasibility of a low molecular weight drug administration. The present study contributes to the nascent knowledge on engineering protein corona as a key to rationally design nanomaterials for biomedical applications.</jats:p>