Plasma Surface Polymerized and Biomarker Conjugated Boron Nitride Nanoparticles for Cancer-Specific Therapy: Experimental and Theoretical Study

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.