表面電漿共振奈米凝膠光敏劑促使神經細胞快速內化應用於抗 Tau 蛋白聚集

Photosensitizers Loaded Plasmonic Nanogels with Rapid Neuronal Internalization for Anti-Tau Aggregation

吳昀瑾(Yun-Chin Wu)

指導教授 ： 江建文

國立臺灣大學/理學院/化學研究所/碩士(2022年)

https://doi.org/10.6342/NTU202201639

摘要

許多文獻證實高反應性的活性氧 (ROS)，是促發神經突觸增長和抑制澱粉樣蛋白β肽聚集和神經元纖維纏結的關鍵因子，神經細胞緩慢內化載體以及半衰期短的光敏劑藥物阻礙光動力治療的應用。本研究設計了一種由螺吡喃 (spiropyran) 和金奈米粒子合成的水凝膠，有望成為有效的光敏劑並抑制Aβ肽聚集。螺吡喃和具有表面電漿共振之金奈米粒子作用後，穩定螺吡喃異構化後的部花青(merocyanine) 結構（拉曼光譜顯示可穩定 1.7 倍）。由於部花青和表面電漿共振的金奈米粒子相互吸引作用，而增加了平面共振結構的穩定性，增加光敏劑的半衰期時間（~24小時），由於水凝膠生物相容性高，螺吡喃@Au 奈米凝膠表現出顯著神經元細胞快速內化（比螺吡喃奈米凝膠快約 3 倍）和應用於抑制32% Aβ肽聚集和神經元纖維纏結。這種高效能光動力治療和快速神經元內化的實驗結果，提高了光致變色分子和等表面電漿共振水凝膠材料應用的機會。

關鍵字

神經退化行性疾病 ； 光敏劑 ； 表面電漿納米粒子 ； 水凝膠 ； 細胞測試 ； 拉曼光譜學

並列摘要

Reactive oxygen species (ROS) has been identified as the key mechanism leading to neurite outgrowth and inhibition of β-amyloid (Aβ) accumulation and neurofibrillary tangles (NFTs). Slow neuronal internalization and short half-life of photosensitizing effects still impede the application of photosensitizers for photodynamic therapy (PDT). Here we demonstrate that the nanogels made of spiropyran and gold nanoparticles can be an effective and long-acting photosensitizer for anti-Aβ accumulation. Spiropyran and plasmonic nanoparticles are rationally integrated to stabilize the isomerization process of spiropyran to merocyanine (a 1.7-fold decrease in Raman intensity). The perfect match configuration of spiropyran and nanoparticles increases the stability of the planar merocyanine structure, resulting in generation of long-lived phototherapy response (an increase stability ~ 24 h). Owing to the compositional benefits, the spiropyran@Au shows remarkable rapid neuronal internalization (~ 3 times faster than the spiropyran) and anti-β-amyloid plaques activity (a 32% reduction of Aβ and NFTs aggregation). This combination of high photodynamic therapy efficiency and quick neuronal translocation reveals intriguing opportunities for applications of photochromic and plasmonic materials

並列關鍵字

Neurodegenerative Diseases ； Photosensitizer ； Plasmonic nanoparticles ； hydrogel ； Bio-testing ； Raman spectroscopy

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