Folic acid-conjugated pH/temperature/redox multi-stimuli responsive polymer microspheres for delivery of anti-cancer drug

The folic acid (FA)-conjugated pH/temperature/redox multi-stimuli responsive poly(methacrylic acidco-N,N-bis(acryloyl)cystamine/poly(N-isopropylacrylamide-co-glycidyl methaaylate-co-N,N-bis(acryloyl)-cystamine) microspheres were prepared by a two-stage distillation-precipitation polymerization with subsequent surface modification with FA. The microspheres were characterized by transmission electron microscopy, dynamical light scattering, Fourier-transform infrared spectra, UV-vis spectra and elemental analysis. The degradation of the functional microspheres could be triggered by a reductive reagent, such as glutathione, due to presence of BAC crosslinker. The drug-loaded microspheres exhibited a pH/temperature/redox multi-stimuli responsive drug release character for doxorubicin hydrochloride as a model anti-cancer drug, which was efficiently loaded into the microspheres with a high loading capacity of 208.0% and an encapsulation efficiency of 85.4%. In vitro drug delivery study indicated that the FA-conjugated microspheres could deliver Dox into MCF-7 cells more efficiently than the microspheres without functionalization of FA. Furthermore, WST-1 assay showed that the microspheres had no obvious toxicity to MCF-7 cells even at a high concentration of 2000 mu g mL(-1). The resultant microsphere may be a promising vector for delivery of anti-cancer drugs as it exhibits a low cytotoxicity and degradability, precise molecular targeting property and multi-stimuli responsively controlled drug release. (C) 2014 Elsevier Inc. All rights reserved.