Ferritin Nanocage-Enabled Detection of Pathological Tau in Living Human Retinal Cells

Abstract

Abstract Background Tauopathies, such as Alzheimer's disease and Frontotemporal Dementia, are debilitating neurodegenerative disorders characterized by cognitive decline. Despite extensive research, effective treatments and significant advancements in managing symptoms have been challenging to achieve. Accurate diagnosis is critical for developing effective therapeutic strategies. Hyperphosphorylated protein units and tau oligomers are recognized as reliable biomarkers for these conditions. This study introduces an innovative approach using nanotechnology to enhance the diagnostic process for tauopathies. We focus on the development and application of humanized ferritin nanocages, a novel nanoscale delivery system, designed to encapsulate and transport a tau-specific fluorophore, BT1, into human retinal cells, for the detection of neurofibrillary tangles in retinal tissue, a key marker of tauopathies. Results The delivery of BT1 into living cells was achieved through the use of humanized ferritin nanocages, a novel delivery system at the nanoscale. The humanized ferritin nanocages demonstrated efficient encapsulation and delivery of BT1 into retinal cells derived from human induced pluripotent stem cells. Our experiments demonstrated the successful colocalization of BT1 with pathological forms of tau in retinal cells derived from human induced pluripotent stem cells, highlighting the potential of this method in identifying tauopathies. Conclusions The employment of ferritin nanocages for the delivery of the BT1 probe represents an important contribution to the field of nanobiotechnology, especially in the context of neurodegenerative disease diagnostics. This method offers a promising tool for the early detection of tau tangles in retinal tissue, with significant implications for improving the diagnosis and management of tauopathies. This study exemplifies the integration of nanotechnology with biomedical science, expanding the frontiers of nanomedicine and diagnostic techniques.