Surface functionalization influences the formation of protein corona on magnetic carbon nanotubes

Nanomaterials have emerged in biomedical applications for the diagnosis and treatment of diseases. Among these materials, carbon nanotubes (CNTs) have been explored for their advantageous properties, including high surface area, stability and potential for surface engineering. In addition, it is crucial to understand the protein corona formed when these materials are administered in vivo, as this adsorbed protein layer can alter their physicochemical characteristics and ultimately influence therapeutic performance. In this work, cytocompatible magnetic carbon nanotubes (M-CNT) covered with bovine serum albumin (M-CNT-BSA) or functionalized with hydrophilic monomers (M-CNT-HL) were investigated concerning their interaction with proteins. Adsorption and titration calorimetry assays using an aqueous human serum albumin (HSA) standard, revealed that HSA–nanotube interactions were strongly dependent on surface chemistry, with the functional coatings, particularly BSA, serving as an external barrier that limited additional protein adsorption. The three materials were also incubated with diluted human serum samples, after which the adsorbed proteins were recovered and characterized. Gel electrophoresis confirmed the presence of the most abundant serum proteins and indicated a marked decrease in HSA adsorption onto M-CNT-BSA. LC–MS/MS proteomic analysis further demonstrated that each surface modification produced a distinct protein corona. A total of 222 proteins were shared among the materials, with M-CNT and M-CNT-HL presenting the highest similarity in protein profile. Notably, M-CNT-HL recruited a higher abundance of dysopsonins, which may be advantageous for in vivo applications. Lastly, the exclusive proteins identified for each nanotube type reinforced the critical role of surface chemistry in governing protein corona formation. • Surface functionalization governs protein interactions on magnetic CNTs. • BSA coating prevents human serum albumin adsorption on M-CNT-BSA. • All synthesized materials form distinct protein coronas. • M-CNT-HL shows enhanced adsorption of dysopsonins.