| 摘要: | 隨著全球人口的老年化，可以預期神經退化性疾病將會影響未來全球的家庭、社會、醫療甚至經濟層面。根據臨床數據顯示神經退化性疾病有許多病徵表現包括神經元減少、突觸數量降低與失能、氧化應激增加和粒線體功能障礙等，因此開發多功能療法是治療神經退化性疾病的重要課題。在本論文中，提出一種嶄新的治療採用神經退化性疾病的方式。利用硝酸蝕刻 (Acid Etching) 製備出具有良好生物相容性且有著迷人的光致發光效應的奈米碳粒子作為載體。再透過修飾不同官能基，改變其螢光光譜，並於提高細胞吞噬率後可作為生物成像的奈米探針。實驗結果顯示，引入PEI官能基作為表面電位的修飾 (CD+PEI) 後，其吞噬率高達99.35%且具備低生物毒性，並能成功載入質體DNA (plasmid DNA；pDNA)，解決pDNA難以進入細胞的限制，大幅提升細胞攝入pDNA之效率，促使神經元突觸增生 (神經元突觸長度大於其兩倍本體尺度之數量達總數50%以上)。另外，可作為攜帶天然的藥物白藜蘆醇的平台，能降低活性氧自由基) 達到減少神經元的損傷之目的。基於奈米碳粒子作為載體結合pDNA和藥物，可提供一種具有多重功能的神經元增生突觸之方式，因此我們認為奈米碳粒子在神經退化性疾病的應用上具有相當大的潛力。;Because of the population ageing in many countries, it can be expected that neurodegenerative diseases will produce many influences for the families, healthcare, society, and even economy aspects in the world. In the clinical data, the neurodegenerative diseases have presented a lot of symptoms, such as the neuronal loss, synaptic dysfunction and loss, oxidative stress increase, mitochondrial dysfunction, and etc. Consequently, developing multifunctional therapies to treat the neurodegenerative diseases is a curial subject. In this thesis, we reported a novel treatment for the neurodegenerative diseases. The carbon nanodot having the good biocompatibility and fascinating photoluminescence were fabricated as a nanocarrier by using the acid etching. After the surface functionalization to alter the fluorescence spectrum and enhance the efficiency of cell uptake, the carbon dots can be used as a nanoprobe for the bioimaging applications. According to the experimental results, the carbon dots with the polyethyleneimine functionalization keep low cytotoxicity and exhibit the superior efficiency of cell uptake, which is up to 99.35%. Through this approach, the presented carbon dots can successfully carry the plasmid DNA (pDNA) into the neurons to improve the low transfection efficiency of the neurons. This great improvement in the pDNA ingesting of neurons also promote their neurite outgrowth. The neurons with the neurite length over twice size of their soma is increased more than 50 %. Furthermore, the carbon dots can also be a platform to carry the natural drug, resveratrol, which is able to reduce the reactive oxygen species to prevent the damage of neurons. The presented carbon dots as the nanocarriers of pDNA and drugs provide a multi-functional treatment for the neurite outgrowth. Therefore, we believe that carbon nanocarriers have great potential in the therapeutic applications of neurodegenerative diseases. |
