Quantum dots in neurotheranostics for the treatment of Alzheimer's disease

Age-related neurodegeneration is one of the primary causes associated with the pathogenesis of Alzheimer's disease (AD). Currently, there are 5.8 million cases of AD worldwide. With the advancement in technology, the paradigm of treating the disease has shifted from one treatment or diagnosis to simultaneously diagnosing as well as treating the disease. Excellent efforts have been made by the scientists towards the development of nanotheranostics. Among them, quantum dots (QDs) have shown promising results due to their nanometer size, which enables them to cross the blood-brain barrier (BBB) and optical properties which help in imaging the environment/pathology inside the brain. Furthermore, their functionalization with the specific biomolecules or coupling with aptamers/proteins/peptides/antibodies offers site-specific detection of pathological biomarkers. The long-lasting, tunable, and strong fluorescence generated by them within the body helps in the selective detection of biomarkers at very low concentrations. This helps in the accurate and early diagnosis of AD. Their multiplexed sensing of multiple markers at a time due to the tunable property of their emission wavelengths, makes it a more specific and sensitive tool over microarray or other assays. Additionally, real-time tracking of drug delivery and parallel treatment of the disease at the targeted site make them a unique theranostic tool over other techniques. This review consolidates recent advances in QDs-based approaches, encompassing their physicochemical properties, blood-brain barrier (BBB) penetration strategies, synthesis, and functionalization techniques. The roles in targeted drug delivery, bioimaging, and biomarker detection, as well as their intrinsic therapeutic actions, including inhibition of amyloid beta formation and tau aggregation, antioxidative effects, and neuroprotection, have also been discussed. Multiple preclinical studies demonstrate the ability of QDs to enhance drug stability, improve BBB transport, enable high-sensitivity imaging of AD biomarkers, and modulate neuroinflammatory responses.