Methods and devices for three-dimensional navigation of magnetic nanoparticles are provided. A method can comprise introducing high-anisotropy magnetic nanoparticles to a mammal and directing the high-anisotropy magnetic nanoparticles towards a target region of the mammal. Direction control is achieved by subjecting the high-anisotropy magnetic nanoparticles to an alternating signal comprising a uniform magnetic field pulse having a strength greater than a coercivity of the high-anisotropy magnetic nanoparticles and a magnetic gradient pulse having a highest strength that is less than the coercivity of the high-anisotropy magnetic nanoparticles and a location of a lowest strength at the target region of the mammal, and the direction of the uniform magnetic field pulse being in an opposite direction of the magnetic gradient pulse.