Degradable one-dimensional dextran-iron oxide nanohybrids for MRI-guided synergistic gene/photothermal/magnetolytic therapy

Abstract The cellular uptake process is critically influenced by the morphology of nanomaterials, which can further impact the therapeutic efficiency. Biodegradable and multifunctional nanomaterials with high cellular uptake efficiency and improved therapeutic effect are highly desirable. Herein, we report one-dimensional polycation-coated nanohybrids Fe3O4@Dex-PGEA (1D FDP) composed of polysaccharide dextran, Fe3O4 nanoparticles and low-toxic β-cyclodextrin-based ethanolamine-functionalized poly(glycidyl methacrylate) (CD-PGEA) via a facile self-assembly method, demonstrating excellent anticancer efficiency. Compared with spherical Fe3O4@Dex-PGEA (s-FDP) as the counterpart, 1D FDP demonstrates good cellular uptake efficiency, which can also rotate under an alternating magnetic field to generate a shear force to destroy tumor cells and exhibits excellent photothermal properties. Taking advantage of the highly efficient delivery, antioncogene p53-loaded 1D FDP nanoplatform shows the tri-modal gene/photothermal/magnetolytic synergistic anticancer effect in vitro and in vivo. Notably, the acidic tumor microenvironment-responsive biodegradation endows the 1D FDP nanohybrids with the capacity of efficient and rapid clearance in vivo, indicating their potential in biomedical application. Moreover, in vivo photothermal imaging and magnetic resonance imaging performance of 1D FDP for tumor accurate diagnosis are also evaluated. The multifunctional 1D FDP nanoplatform with pH-responsive degradability provides a promising candidate to realize enhanced gene/photothermal/magnetolytic therapy.