Development of versatile nanoplatforms for
cancer theranostics remains a hot topic in the area of nanomedicine. We report here a general approach to create
polyethylenimine (PEI)-based hybrid
nanogels (NGs) incorporated with ultrasmall
iron oxide (Fe3O4) nanoparticles (NPs) and
doxorubicin for T1-weighted MR imaging-guided
chemotherapy of
tumors. In this study, PEI NGs were first prepared using an inverse
emulsion approach along with Michael addition reaction to cross-link the NGs, modified with
citric acid-stabilized ultrasmall Fe3O4 NPs through 1-ethyl-3-(3-(dimethylamino)propyl)
carbodiimide hydrochloride (EDC) coupling, and physically loaded with anticancer drug
doxorubicin (DOX). The formed hybrid NGs possess good water dispersibility and colloidal stability, excellent DOX loading efficiency (51.4%), pH-dependent release profile of DOX with an accelerated release rate under acidic pH, and much higher r1 relaxivity (2.29 mM-1 s-1) than free ultrasmall Fe3O4 NPs (1.15 mM-1 s-1). In addition, in contrast to the drug-free NGs that possess good cytocompatibility, the DOX-loaded hybrid NGs display appreciable therapeutic activity and can be taken up by
cancer cells in vitro. With these properties, the developed hybrid NGs enabled effective inhibition of
tumor growth under the guidance of T1-weighted MR imaging. The developed hybrid NGs may be applied as a versatile nanoplatform for MR imaging-guided
chemotherapy of
tumors.