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標題: 活體中光纖激發促進含奈米金粒子光熱感應微脂體定點釋放
In vivo fiber-optic triggered release of photo-thermal responsive liposome with gold nanoparticles
作者: 黃惠鈴
Huang, Huei-Ling
關鍵字: 光纖耦合促進釋放
Topical release triggered by fiber-coupled laser excitation
Photo-thermal responsive liposome
Gold nanoparticles (AuNPs)
Surface plasmon resonance (SPR)
Concentration quenching or Self-quenching of fluorescein
出版社: 生醫工程研究所
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摘要: 本研究探討以200 μm光纖導引65 mW 532 nm雷射激發光至活體內定點,主動促進含奈米金粒子光熱感應微脂體的釋放條件與趨勢,以期能改善微脂體於活體中定點釋放的效率。此微脂體包覆自滅濃度螢光指示劑 75 mM fluorescein後,經光激發後藉由fluorescein釋放後稀釋造成的螢光強度上昇(自滅現象解除)來做為了解其定點釋放的趨勢。在活體外仿生水浴環境下,含疏水性奈米金粒子光熱感應微脂體在40分鐘達到約74.53 ±1.63 %的釋放率,高於對照組的不含奈米金粒子微脂體14.53±3.17 %的釋放率。在裸鼠融植瘤模型活體實驗中,經活體螢光影像系統(IVIS)測得擴散趨勢得知,純螢光物擴散速率較快,於注入後10分鐘內癌組織位置平均螢光強度(濃度指示)銳減至20%以下;包覆螢光物光熱感應微脂體因擴散速率較慢,於注入後於癌組織位置能維持強度(濃度指示)>40%達30分鐘以上,且因拮抗作用中訊號上升的趨勢(螢光物由癌組織中心擴散至近體表處增加IVIS訊號)大於下降的趨勢(螢光物擴散降低濃度減弱IVIS訊號),於注入後20-40分鐘間呈現每像數平均訊號值大於初始訊號值的情形。進一步以自滅濃度(75mM)與最強螢光濃度(1mM) fluorescein包覆光熱感應微脂體直接於腫瘤植入物環境內光纖導光激發促進釋放的差異,自滅濃度組照光後整體螢光強度和面積均大幅上升(3-10倍),而最強螢光濃度組照光後則呈現逐步下降的趨勢,確認導光主動促進釋放的成效(而非螢光物由深層移至表面造成的螢光上升)。最後比較含金微脂體與不含金微脂體受光纖導光激發釋放的差異,測得含奈米金粒子受激發釋放程度高於對照組達190-260%,證實奈米金粒子能發揮將光能轉為熱能,有助微脂體因溫度變化達到增加通透度相變化的臨界溫度,促進包覆螢光物釋出效率。
The aim of the research is to investigate the strategy in applying fiber-optic triggered release of photothermal responsive gold nanoparticles (AuNPs) embedded liposome with 200 μm fiber and 65 mW 532 nm for topical release in vivo. The pattern of topical release triggered by laser excitation conveyed through optical fiber was monitored by fluorescence increase from dilution of 75mM fluorescein encapsulated in liposome. The AuNPs embedded liposome showed more efficient triggered release (74.53 ±1.63 % in 40 minutes) than liposome without AuNPs (14.53±3.17 %) in vitro (37℃water bath). In nude mice xenografts study, the free fluorophore exhibited more rapid diffusion and caused significant signal decay (average pixel intensity dropped to less than 20 % of pixel with maximal intensity in 10 minutes) around tumor region under fluorescent imaging monitoring; the fluorophore encapsulated liposome demonstrated slower diffusion and maintaining average pixel intensity more than 40 % of pixel with maximal intensity for more than 30 minutes, with average intensity raise between 20 to 40 minutes due to the signal increase tendency (fluorophore administrated in the center of tumor diffused to near skin surface area converting stronger IVIS signal) surpassing the declining tendency (dilution of fluorophore by diffusion) in the antagonistic actions. The topical release triggered by laser excitation conveyed through optical fiber was confirmed by observing significant expansion of fluorophore covering area and raise of average intentsity (3-10 folds) from 75mM fluorescein encapsulated liposome; while gradually decay of both indice from 1 mM fluorescein encapsulated liposome (it verified that the light triggered fluorescence increase resulting from fluorophore release, and not fluorophore administrated in the center of tumor diffused to near skin surface area converting stronger IVIS signal). The AuNPs is proved to facilitate the conversion of light energy into heat with AuNPs embedded liposome showing 190-260% higher efficiency in triggered release than liposome without AuNPs.
其他識別: U0005-2008201320134100
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