Periodate-Mediated Cross-Linking for the Preparation of Catechol Conjugated Albumin Nanoparticles Used for in Vitro Drug Delivery

Abstract

Conjugation of serum albumin protein with catechol-containing dopamine molecules provides an alternative method for the preparation of albumin nanoparticles (NPs). A commonly used desolvation method utilizes glutaraldehyde as a cross-linking agent. Here, the catechol cross-linking mechanism is used instead of glutaraldehyde providing advantages to prevent toxicity and an undesirable reaction of glutaraldehyde with cargo molecules. Covalent cross-linking between dopamine conjugated bovine serum albumin (D-BSA) proteins was obtained in the presence of sodium periodate (NaIO4) as an oxidizer. As a result, spherical D-BSA NPs with a uniform size distribution of around 100 nm in diameter and negative zeta potential around −28 mV were prepared. Optimal conditions were reached when a dopamine:IO4- molar ratio of 2:1, pH 7.4 of the medium, and acetone as the desolvating agent were used. Furthermore, the obtained NPs display antioxidant properties, have rapid biodegradability in the presence of trypsin, and have a high doxorubicin (DOX) loading (9.1%) with a sustainable drug release. DOX loaded D-BSA NPs also caused up to 90% breast cancer cell (MCF-7) death within 24 h. These results show that drug carrying albumin NPs can alternatively be prepared via covalently cross-linked catechol groups and used in drug delivery studies. © 2025 American Chemical Society.