Optical Nanosensor for Intracellular and Intracranial Detection of Amyloid-Beta
Merav Antman‐Passig, Eitan Wong, Georgia Frost, Christian Cupo, Janki Shah, Albert S. Agustinus, Ziyu Chen, Chiara Mancinelli, Maikel Kamel, Thomas Li, Lauren A. Jonas, Yue‐Ming Li, Daniel A. Heller
Abstract
Amyloid-beta (Aβ) deposition occurs in the early stages of Alzheimer's disease (AD), but the early detection of Aβ is a persistent challenge. Herein, we engineered a near-infrared optical nanosensor capable of detecting Aβ intracellularly in live cells and intracranially in vivo. The sensor is composed of single-walled carbon nanotubes functionalized with Aβ wherein Aβ-Aβ interactions drive the response. We found that the Aβ nanosensors selectively responded to Aβ via solvatochromic modulation of the near-infrared emission of the nanotube. The sensor tracked Aβ accumulation in live cells and, upon intracranial administration in a genetic model of AD, signaled distinct responses in aged mice. This technology enables the interrogation of molecular mechanisms underlying Aβ neurotoxicity in the development of AD in living systems.