Carbon Dots for Drug Delivery and Treatment of Alzheimer’s Disease

Wei Zhang

This dissertation investigates the potential of carbon dots (CDs) as drug carriers and therapeutic agents for Alzheimer's disease (AD). CDs possess favorable properties such as biocompatibility, water dispersion, low cytotoxicity, tunable surface chemistry, and efficient BBB penetration. Chapter 2 explores the synthesis, modification, characterization, and biomedical applications of CDs for delivering memantine hydrochloride (MH), an FDA-approved drug for moderate to severe AD. CDs also function as nanodrugs, in chapter 3, using Congo red as a precursor, demonstrating their ability to inhibit both Aβ and tau aggregation. In vitro and in vivo experiments showed that MH-conjugated CDs successfully inhibited tau aggregation, while Congo red-based CDs simultaneously inhibited Aβ and tau aggregation. Zebrafish model was used to evaluate the CDs' BBB penetration and therapeutic delivery to the central nervous system (CNS). Beyond drug delivery, CDs show promise as gene delivery vectors. Non-viral vectors, such as CDs, offer advantages over viral vectors, including reduced immune response, the ability to carry larger genetic materials, protection of genetic materials during delivery, and better reproducibility. Chapter 4 explores a new type of CDs, termed PCDs, synthesized using citric acid and pentaethylenehexamine (PEHA) as precursors. Due to electrostatic interactions with DNA and groove adsorption, PCDs effectively bind with DNA. In vitro studies demonstrated high transfection efficiency with minimal cytotoxicity. Given their ability to cross the BBB and enter the CNS of zebrafish, PCDs show potential as gene vectors for treating brain diseases through gene and drug delivery.

Carbon Dots for Drug Delivery and Treatment of Alzheimer’s Disease

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