Phenol-Boronic surface functionalization of gold nanoparticles; to induce ROS damage while inhibiting the survival mechanisms of cancer cells

The natural phenolic molecule caffeic acid, show promising effects on biological systems as an anti/pro-oxidant, anti-cancer, and anti-inflammatory agent. In nanoparticle functionalization designs, most organic nanoparticle coatings are utilized only for their ability to carry chemotherapeutics and targeting ligand. In this study, UV-light and auto-oxidation polymerization of caffeic acid on top of as-prepared gold nanoparticles was utilized to bring about a 5 nm multifunctional coating. The resulting polycaffeic acid (PCA) coating was used to conjugate both boronic acid containing compounds, chemotherapeutic bortezomib (BTZ) and cancer targeting ligand folate, while inducing mitochondrial reactive oxygen species that can damage intracellular proteins and DNA. This complements the drug payload, bortezomib's cell survival inhibition properties. The drug, targeting ligand, and coating complexation are all pH cleavable under acidic pH condition (<5.0) which can be found in a tumor and endosomal microenvironment. The in vitro and in vivo experiments demonstrated cancer cytotoxicity and tumor inhibiting properties of the developed nanomedicine.