On-command controlled drug release by diels-Alder reaction using Bi-magnetic core/shell nano-carriers

Abstract

A novel bi-functional thermo-responsive system, consisting of core/shell bi-magnetic nanoparticles with furan surface functionality, is bonded with N-(2-Carboxyethyl)maleimide through Diels-Alder reaction. The chemotherapeutics doxorubicin is attached onto the surface, with a high loading efficiency of 92%. This system with high responsiveness to a high frequency external alternating magnetic field shows a very good therapeutic efficiency in hyperthermia and drug release at relatively low temperatures (50°C). Polyhedron-shaped bi-magnetic nanoparticles (Zn_0.4Co_0.6Fe₂O₄@Zn_0.4Mn_0.6Fe₂O₄) exhibit a significant increase of the specific energy absorption rate up to 455W/g compared with the core nanoparticles (200W/g). Real-time florescence spectroscopy studies demonstrate rapid release of doxorubicin up to 50% in 5min and up to 92% after 15min upon exposure to high frequency external alternating magnetic field. The stability is evaluated for 8 weeks in phosphate buffer saline with a doxorubicin payload of 85%. In vitro studies using standard MTT cell assays with HeLa and Hep G2 lines prove an excellent biocompatibility with about 90% of cell viability after 24h of treatment within the highest concentration of functionalized magnetic nanoparticles (200μg/mL). The results indicate a controlled drug release mediated by thermo-responsive switching under applied alternating magnetic field.

Keywords: Bi-magnetic nanoparticles; Controlled release; Core/shell; Diels-Adler; Doxorubicin.