Encapsulating magnetic and fluorescent mesoporous silica into thermosensitive chitosan microspheres for cell imaging and controlled drug release in vitro

In this study, for the first time, multifunctional inorganic/organic core/shell hybrid microspheres consisted of Fe3O4 nanoparticles/CdTe quantum dots dual-embedded mesoporous silica nanocomposites (MQ-MSN) as cores and P(N-isopropylacrylamide)-graft-Chitosan microgels (PNIPAM-g-CS) as shells were prepared by copolymerization of NIPAM and CS in the presence of MQ-MSN. The preparation of microspheres (i.e., MQ-MSN/PNIPAM-g-CS) included three stages. First, Fe3O4/CdTe nanocomposites (MQ NCs) were prepared by self-assembly of electrostatic adsorption. Second, MQ NCs were encapsulated into silica spheres by modified Stober method to obtain MQ-MSN. Third, NIPAM monomers were initiated to fabricate PNIPAM networks with MQ-MSN distributed below the lower critical solution temperature (LCST) of PNIPAM, and then PNIPAM reacted with CS to form PNIPAM-g-CS copolymers above the LCST, meanwhile the PNIPAM networks collapsed to form microspheres, resulting in the MQ-MSN encapsulated into microspheres. The microspheres were systematically characterized, displaying perfect magnetic/fluorescent properties and thermo-sensitivity. HepG2 cancer cells treated with the microspheres revealed bright fluorescence imaging. Both the efficiency and capacity of Adriamycin (ADM) loaded into the microspheres were gradually increased with ADM concentration increasing. The ADM cumulative release in vitro from ADM-loaded microspheres was significant at a higher temperature (or a lower pH). The released ADM still maintained high anticancer activity, and the blank microsphere carriers hardly produced toxicity to HepG2 cells. Hence, the multifunctional microspheres exhibited a promising application especially as thermo/pH-sensitive drug carriers for in vivo therapy. (C) 2013 Elsevier B.V. All rights reserved.