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.