Chitosan nanoparticles for combined drug delivery and magnetichyperthermia: From preparation to in vitro studies

Chitosan nanoparticles (CSNPs) ionically crosslinked with tripolyphosphate salts (TPP) were employedas nanocarriers in combined drug delivery and magnetic hyperthermia (MH) therapy. To that aim, threedifferent ferrofluid concentrations and a constant 5-fluorouracil (5-FU) concentration were efficientlyencapsulated to yield magnetic CSNPs with core-shell morphology. In vitro experiments using normalcells, fibroblasts (FHB) and cancer cells, human glioblastoma A-172, showed that CSNPs presented a dose-dependent cytotoxicity and that they were successfully uptaken into both cell lines. The application ofa MH treatment in A-172 cells resulted in a cell viability of 67–75% whereas no significant reduction ofcell viability was observed for FHB. However, the A-172 cells showed re-growth populations 4 h after theapplication of the MH treatment when CSNPs were loaded only with ferrofluid. Finally, a combined effectof MH and 5-FU release was observed with the application of a second MH treatment for CSNPs exhibitinga lower amount of released 5-FU. This result demonstrates the potential of CSNPs for the improvementof MH therapiesThe authors would like to express their appreciation to D. Gómezand P. Posadas for FESEM microscopy and AFM measurements andR. Ramirez for cell culture studies. V. Zamora-Mora thanks CSICfor a JAE predoc fellowship and R. Hernández thanks MEC for aRamon y Cajal contract. G.F. Goya aknowledges financial supportfrom the Fondo Europeo de Desarrollo Regional and Gobierno de Aragón. Financial support from the Spanish Ministerio de Economíay Competitividad (MINECO) (projects MAT 2011-24797, MAT2010-19326 and HelloKit INNPACTO) is also acknowledged.Peer Reviewe