An efficient synthetic route for a soluble silsesquioxane-daunorubicin conjugate

Abstract

Anthracycline conjugates, covalently bonded to the inorganic cage of polyhedral oligomeric silsesquioxanes, were successfully synthesized by reacting the primary amino group of daunorubicin and octakis-[3-(2-succinic anhydride)propyl,dimethylsiloxy]octasilsesquioxane (POSSAn) with a molar ratio 8:1, 3:1, and 1:1. The synthetic pathway involved hydrosilylation of octakis-(hydridodimethyl-siloxy)octasilsesquioxane (H-POSS) with allyl succinic anhydride, in the presence of Karstedt’s catalyst. POSS-DAU nanoparticles were used as the carriers for the anticancer drug daunorubicin (DAU), due to their high drug loading properties and comparatively low side effects. The coupling reaction proceeds quantitatively and leads to a highly soluble conjugate. The kinetics of the reaction was studied using FTIR spectroscopy, by observing changes to relevant peaks. The amount of DAU grafted in the POSS-DAU nanoparticles varied from 27wt% to 66wt%. The products were characterized using 1H, 13C, 29Si NMR, FTIR spectroscopy, SEM, and MALDI-Toff analysis. Mass spectrometry with electrospray ionization techniques (ESI) in the negative ion mode was successfully used for recording the mass spectra of the POSS-DAU nanoparticles. The hydrodynamic diameter and zeta potential of the POSS-DAU nanoparticles were determined by the DLS method.