Enhanced Targeted Delivery of Cyclodextrin-Based Supermolecules by Core-Shell Nanocapsules for Magnetothermal Chemotherapy.

In this study, double-emulsion capsules (DECs) capable of concealing drug-incorporated targeted-supermolecules are developed to achieve "on-demand" supermolecule release and enhanced sequential targeting for magneto-chemotherapy. These water-in-oil-in-water DECs less than 200 nm in diameter are synthesized using a single component of PVA (polyvinyl alcohol) polymer and the magnetic nanoparticles, which are capable of encapsulating large quantities of targeted supermolecules composed of palitaxel-incorporated beta-cyclodextrin decorated by hyaluronic acid (HA, a CD44-targeting ligand) in the watery core. The release profiles (slow, sustained and burst release) of the targeted supermolecules can be directly controlled by regulating the high-frequency magnetic field (HFMF) and polymer conformation without sacrificing the targeting ability. Through an intravenous injection, the positive targeting of the supermolecules exhibited a 20-fold increase in tumor accumulation via the passive targeting and delivery of DECs followed by positive targeting of the supermolecules. Moreover, this dual-targeting drug-incorporated supermolecular delivery vehicle at the tumor site combined with magneto-thermal therapy suppressed the cancer growth more efficiently than treatment with either drug or supermolecule alone.