Anodic Titanium Dioxide Nanotubes for Magnetically Guided Therapeutic Delivery

Hollow titanium dioxide (TiO(2)) nanotubes offer substantially higher drug loading capacity and slower drug release kinetics compared to solid drug nanocarriers of comparable size. In this report, we load TiO(2) nanotubes with iron oxide nanoparticles to facilitate site-specific magnetic guidance and drug delivery. We generate magnetic TiO(2) nanotubes (TiO(2)NTs) by incorporating a ferrofluid containing Ø ≈ 10 nm iron oxide nanoparticles in planar sheets of weakly connected TiO(2) nanotubes. After thermal annealing, the magnetic tubular arrays are loaded with therapeutic drugs and then sonicated to separate the nanotubes. We demonstrate that magnetic TiO(2)NTs are non-toxic for HeLa cells at therapeutic concentrations (≤200 µg/mL). Adhesion and endocytosis of magnetic nanotubes to a layer of HeLa cells are increased in the presence of a magnetic gradient field. As a proof-of-concept, we load the nanotubes with the topoisomerase inhibitor camptothecin and achieve a 90% killing efficiency. We also load the nanotubes with oligonucleotides for cell transfection and achieve 100% cellular uptake efficiency. Our results demonstrate the potential of magnetic TiO(2)NTs for a wide range of biomedical applications, including site-specific delivery of therapeutic drugs.