A new low-pressure plasma-based approach to activate the surface of BN nanoparticles (BNNPs) in order to facilitate the attachment of folate acid (FA) molecules for cancer-specific therapy is described. Plasma treatment of BNNPs (BNNPs PT ) was performed in a radiofrequency plasma reactor using ethylene and carbon dioxide monomers. The carboxyl groups deposited on the surface of BNNPs PT were activated by N,N'-dicyclohexylcarbodiimide (DCC) and participated in the condensation reaction with ethylene diamine (EDA) to form a thin amino-containing layer (EDA-BNNP PT ). Then, the DCC-activated FA was covalently bonded with BNNPs PT by a chemical reaction between amino groups of EDA-BNNPs PT and carboxyl groups of FA. Density functional theory calculations showed that the pre-activation of FA by DCC is required for grafting of the FA to the EDA-BNNPs PT . It was also demonstrated that after FA immobilization, the electronic characteristics of the pteridine ring remain unchanged, indicating that the targeting properties of the FA/EDA-BNNPs PT nanohybrids are preserved.Author Contributions: E.S.P. performed NH 2 -functionalization and FA conjugation, as well as obtained FT ICR MS spectrum and prepared the manuscript, L.Y.A. and P.B.S. performed simulations and described the results, P.V.K.-K. carried out plasma surface polymerization, A.M.K. fabricated BN nanoparticles by CVD and performed SEM and EDS spectroscopy characterization, J.P. and A.M. obtained XPS spectra and performed their analysis, K.Y.G. performed FTIR spectroscopy, D.V.S. analyzed the results and edited the manuscript.