Amino Oxidase Hard Protein Corona with Metabolic-Triggered Intracellular Biocatalysis

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 catalyzing 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's biological activity induced intracellular oxidative stress, leading to the activation of the 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 (>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.