Department of Biochemical Sciences, Sapienza University of Rome, 00185, Rome, Italy.
Center for Life Nano- and Neuro-Science, Istituto Italiano di Tecnologia, 00161, Rome, Italy.
Sci Rep. 2024 May 21;14(1):11533. doi: 10.1038/s41598-024-62188-8.
Tauopathies, including Alzheimer's disease and Frontotemporal Dementia, are debilitating neurodegenerative disorders marked by cognitive decline. Despite extensive research, achieving effective treatments and significant symptom management remains challenging. Accurate diagnosis is crucial for developing effective therapeutic strategies, with hyperphosphorylated protein units and tau oligomers serving as reliable biomarkers for these conditions. This study introduces a novel approach using nanotechnology to enhance the diagnostic process for tauopathies. We developed humanized ferritin nanocages, a novel nanoscale delivery system, designed to encapsulate and transport a tau-specific fluorophore, BT1, into human retinal cells for detecting neurofibrillary tangles in retinal tissue, a key marker of tauopathies. The delivery of BT1 into living cells was successfully achieved through these nanocages, demonstrating efficient encapsulation and delivery into retinal cells derived from human induced pluripotent stem cells. Our experiments confirmed the colocalization of BT1 with pathological forms of tau in living retinal cells, highlighting the method's potential in identifying tauopathies. Using ferritin nanocages for BT1 delivery represents a significant contribution to nanobiotechnology, particularly in 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.
tau 病，包括阿尔茨海默病和额颞叶痴呆，是使人衰弱的神经退行性疾病，其特征是认知能力下降。尽管进行了广泛的研究，但实现有效的治疗和显著的症状管理仍然具有挑战性。准确的诊断对于制定有效的治疗策略至关重要，过度磷酸化的蛋白单元和 tau 寡聚体是这些疾病的可靠生物标志物。本研究介绍了一种使用纳米技术增强 tau 病诊断过程的新方法。我们开发了人源化铁蛋白纳米笼，这是一种新颖的纳米级递药系统，旨在封装并将 tau 特异性荧光团 BT1 递送至人视网膜细胞中，以检测视网膜组织中的神经原纤维缠结，这是 tau 病的一个关键标志物。通过这些纳米笼成功地将 BT1 递送至活细胞中，证明了其对人诱导多能干细胞衍生的视网膜细胞的有效封装和递送。我们的实验证实了 BT1 与人视网膜活细胞中病理性 tau 的共定位，突出了该方法在鉴定 tau 病方面的潜力。使用铁蛋白纳米笼递送 BT1 代表了纳米生物技术的重大贡献，特别是在神经退行性疾病诊断方面。该方法为在视网膜组织中早期检测 tau 缠结提供了一种有前途的工具，对改善 tau 病的诊断和管理具有重要意义。本研究展示了纳米技术与生物医学科学的融合，扩展了纳米医学和诊断技术的前沿。
