Affiliation: | 1. Institute of Biological and Medical Imaging, Helmholtz Zentrum München, 85764 Neuherberg, Germany;2. Institute of Developmental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany;3. Department of Nuclear Medicine, Technical University of Munich, 81675 München, Germany;4. Chair for Biological Imaging, Technical University of Munich, 81675 Munich, Germany;5. Chair of Analytical Chemistry and Water Chemistry, Technical University of Munich, 81377 München, Germany;6. Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany;7. Faculty of Physics and Center for Nanointegration (CENIDE), University of Duisburg‐Essen, 47057 Duisburg, Germany;8. National University of Science and Technology ?MISIS?, 119049 Moscow, Russia;9. School of Mathematics and Science, Institute for Biology and Environmental Sciences IBU, Carl von Ossietzky University of Oldenburg, 26129 Oldenburg, Germany;10. Research Center Neurosensory Science, Carl von Ossietzky Universit?t Oldenburg, 26111 Oldenburg, Germany |
Abstract: | Nanomaterials are of enormous value for biomedical applications because of their customizable features. However, the material properties of nanomaterials can be altered substantially by interactions with tissue thus making it important to assess them in the specific biological context to understand and tailor their effects. Here, a genetically controlled system is optimized for cellular uptake of superparamagnetic ferritin and subsequent trafficking to lysosomes. High local concentrations of photoabsorbing magnetoferritin give robust contrast in optoacoustic imaging and allow for selective photoablation of cells overexpressing ferritin receptors. Genetically controlled uptake of the biomagnetic nanoparticles also strongly enhances third‐harmonic generation due to the change of refractive index caused by the magnetite–protein interface of ferritins entrapped in lysosomes. Selective uptake of magnetoferritin furthermore enables sensitive detection of receptor‐expressing cells by magnetic resonance imaging, as well as efficient magnetic cell sorting and manipulation. Surprisingly, a substantial increase in the blocking temperature of lysosomally entrapped magnetoferritin is observed, which allows for specific ablation of genetically defined cell populations by local magnetic hyperthermia. The subcellular confinement of superparamagnetic ferritins thus enhances their physical properties to empower genetically controlled interrogation of cellular processes with deep tissue penetration. |