Folic acid-conjugated temperature and pH dual-responsive yolk/shell microspheres as a drug delivery system

Abstract

A facile and effective approach was developed to fabricate folic acid-conjugated temperature-sensitive hollow microspheres with movable pH-responsive cores for a targeted drug delivery system (DDS) via two-stage distillation precipitation polymerization. The yolk/shell structure of the microspheres obtained was revealed by transmission electron microscopy (TEM). Their monodisperse poly(methacrylic acid-co-ethyleneglycol dimethacrylate) (P(MAA-co-EGDMA)) microgel cores expressed obvious pH stimulus-response characteristics from Dynamical Light Scattering (DLS) analysis, and their functional crosslinked poly(N-isopropylacrylamide) (PNIPAM) shells exhibited obvious temperature stimulus-responses with diameters related to the degree of crosslinking and monomer proportion. Their independent temperature and pH dual-stimulus controlled release of drug molecules (using a model anti-cancer drug, doxorubicin (DOX)) was also investigated in simulated human body fluids. Meanwhile, the FA conjugated targeting temperature-sensitive hollow microspheres with pH-responsive cores expressed excellent biocompatibility on HepG2 cells. Consequently, the precise molecular targeting properties produced by the surface folic acid groups and the independent temperature and pH dual-stimulus responsive characteristics from the unique yolk/shell structure offers promise for cancer treatment.