Ultrasmall T1-T2 MR multimodal imaging nanoprobes for the detection of β-amyloid aggregates in Alzheimer's disease mice.

: Alzheimer's disease (AD) is an irreversible brain disorder and imposes a severe burden upon patients and the public-health system. Most research efforts have focused on the search for effective therapeutic drugs, but it is time to pursue efficient early diagnosis based on the reasonable assumption that AD may be easier to prevent than reverse. Recent studies have shown that there are several probes for detecting amyloid-β (Aβ) plaques, one of the neuropathological hallmarks found in AD brain. However, it is still a great challenge for non-radioactive, sensitive detection and location of Aβ plaques by using brain imaging with high spatial resolution. Herein, phenothiazine derivatives-conjugated sub-5 nm ultrasmall ferrite nanoprobes (UFNPs@PEG/PZD) are designed and prepared for efficient T1-T2 MR multimodal imaging of Aβ plaques. UFNPs@PEG/PZD not only possess high binding affinity to Aβ plaques but also exhibit excellent properties of r1 and r2 relaxivities. This study thus provides a promising ultrasmall nanoplatform as an Aβ-targeting multimodal imaging probe for the application of early diagnosis of AD.