Magnetic Fullerene-DNA/Hyaluronic Acid Nanovehicles with Magnetism/Reduction Dual-Responsive Triggered Release

We created the dual-responsive nanovehicle that can effectively combine and abundantly utilize magnetic and glutathione (GSH)-reductive triggers to control the drug delivery and achieve more intelligent and powerful targeting. In the nanovehicles, paramagnetic fullerene (C₆₀@CTAF) was prepared via one-step modification of fullerene with magnetic surfactant CTAF by hydrophobic interaction for the first time. The perfect conjugation of C₆₀ and CTAF increased the solubility or dispersity of fullerenes and qualified CTAF with more powerful assembly capability with DNA. DNA molecule in the nanovehicles acted as an electrostatic scaffold to load anticancer drug Dox as well as the important building block for assembly with C₆₀@CTAF into C₆₀@CTAF/DNA. The further combination of deshielding and targeting functions in reduction-responsive disulfide modified HA-SS-COOH coating on C₆₀@CTAF/DNA complexes could reduce the agglomeration and regulate the morphology of C₆₀@CTAF/DNA complexes from irregular microstructures to more uniform ones. More importantly, the introduction of HA-SS-COOH provided a response to a simulating reductive extra-tumoral environment by efficient cleavage of disulfide linkages by GSH and site-specific drug delivery to HepG2 cells. Amazingly, the final nanovehicles presented an increased magnetic susceptibility compared with paramagnetic CTAF, and they "walked" under an applied magnetic field. Because of their facile fabrication, rapid responsiveness to extra tumoral environment, and external automatic controllability by external magnet, the drug delivery nanovehicles constructed by magnetic fullerene-DNA/hyaluronic acid might be of great interest for making new functional nucleic-acid-based drug carriers.