| Author: | Gu, Yutian |
| Title: | ROS scavenging based multifunctional nanoparticles for neurological disorders therapy |
| Advisors: | Yang, Mo (BME) |
| Degree: | Ph.D. |
| Year: | 2024 |
| Subject: | Nervous system -- Diseases -- Treatment Active oxygen Oxidative stress Nanoparticles Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Biomedical Engineering |
| Pages: | xxii, 154 pages : color illustrations |
| Language: | English |
| Abstract: | Neurological disorders have been challenged to improve the prognosis of diseases, such as neuron inflammation, brain tumors, Alzheimer's disease (AD), and Parkinson's disease (PD) in the central nervous system (CNS) compared to other body parts. The exacerbation of these conditions within the CNS, compared to other parts of the body, is often attributed to cerebral biochemical impairment, a notable factor of which is oxidative stress (OS). OS, a chemically induced process instigated by an overproduction of reactive oxygen species (ROS), results in a detrimental accumulation of oxidative damage at the cellular level. Therapeutically, ROS-scavenging nanoparticles show promising potential for intervention in such disorders. This paper presents an analysis of two synthesized multifunctional nanoparticles, based on ROS-scavenging mechanisms, and their applications in imaging and therapy. The findings could contribute significantly to devising efficacious therapeutic strategies for CNS disorders associated with oxidative stress. The initial part of the study is devoted to a neuron-targeting multifunctional nanocomposite that amalgamates dual imaging with ROS-scavenging-based AD therapy. This nanocomposite was synthesized from tannic acid (TA), IR780, and DSPE-PEG-COOH through self-assembly to form IR780@TA nanoparticles (NP), which were then coated with manganese ions (Mn²⁺) and linked with TPL for Neuron cell targeting. The results demonstrate that this nanocomposite effectively scavenges ROS and reduces the degree of hyperphosphorylated and aggregated tau proteins both in vitro and in vivo. Moreover, the nanocomposite significantly ameliorated memory disorders in AD model rats. This approach employs neuron-targeted multifunctional nanocomposites to scavenge ROS and depolymerize hyperphosphorylated proteins, serving as a promising avenue for future AD treatment. In addition, a novel therapeutic approach for neuronal inflammation treatment is reported. This strategy involves the use of a phenylenediamine (PDA)-based carbon nanodots (CDs) nanoparticle and overexpressing microRNA-124 (miR-124) loaded in M2 microglia-derived exosomes. The PDA-CD demonstrated a significant ROS scavenging ability, underscoring their potential as ROS scavengers. Furthermore, overexpression of miR-124 has been documented to reduce inflammation and promote neuroprotection in various neurological disorders. M2 microglia, identified as critical regulators of the CNS inflammatory response were utilized in this study as a delivery system for the PDA CDs loaded with miR-124, targeting inflamed neurons both in vitro and in vivo. This study presents a promising therapeutic strategy for neuronal inflammation, a condition common to several NDs. |
| Rights: | All rights reserved |
| Access: | open access |
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