| 摘要: | 中孔洞二氧化矽奈米粒子因其可調節的孔徑和易於修改的表面功能性，使其成為藥物遞送的理想載體，能提供高表面積和穩定性，並在生物醫學領域具有廣闊的應用前景。本研究選擇了Astaxanthin（蝦紅素）和Mivebresib（ABBV-075）這兩種藥物，因其獨特的藥物特性和顯著的治療潛力而成為研究的焦點。Astaxanthin和Mivebresib分別代表了抗氧化劑和抗癌藥物，儘管它們在治療目的和機制上有所不同，但在疏水性和藥物傳遞挑戰方面具有共同特性。Astaxanthin和Mivebresib在水環境中的溶解度和穩定性低，導致口服用藥後生物利用效率差。為了提高疏水性藥物在體內的生物利用率，我們採用了一種人工合成的奈米材料，即中孔洞二氧化矽奈米粒子 （Mesoporous Silica Nanoparticles，MSN）。透過表面修飾辛基三乙氧基矽烷 (Triethoxy (octyl) silane, C8-silane) 、聚乙二醇 （Polyethylene Glycol, PEG） 和三甲基氯化銨 （Trimethyl[3- (trimethoxysilyl) propyl]ammonium Chloride, TA） 於MSN孔洞及表面，我們創造了一個疏水環境，提高疏水性藥物的負載能力且提升材料在血液中的運輸效果和增加細胞吞噬能力。
我們合成的C8-MSN-PEG/TA材料經過鑑定，粒徑大小約為25 nm。細胞實驗顯示材料及Astaxanthin無毒性反應，且C8-MSN-PEG/TA材料具有良好的細胞吞噬效果。Flow cytometry抗氧化測試結果顯示，經由C8-MSN-PEG/TA材料攜帶Astaxanthin的組別，其抗氧化效果優於直接使用Astaxanthin的組別。Mivebresib經C8-MSN-PEG/TA裝載後，Mivebresib仍能有效抑制癌細胞生長。這些結果表明，C8-MSN-PEG/TA材料能顯著提升疏水性藥物的生物利用率和治療效果。
在第二章研究中，我們探討了病毒樣中孔洞矽奈米粒子 （Virus-like Mesoporous Silica Nanoparticles， vMSN）作為mRNA載體在動物和細胞實驗中的應用效果。首先，在動物實驗中，我們將Luc-mRNA、聚乙烯亞胺和vMSN混合，並對母鼠進行單次腹腔內注射。結果顯示，vMSN 載體顯著提高了mRNA的治療效果，表現出更強的螢光信號。隨後，我們進行了細胞體外治療實驗。結果顯示，經過vMSN載體處理的mRNA在螢光顯微鏡下表現出更高的治療效果。流式細胞儀的分析進一步證實，vMSN 顯著提高了mRNA在細胞內的表達水平。這些結果表明，vMSN不僅能有效攜帶和保護mRNA，還能顯著提升其在生物體內和體外的治療效果。本研究證實了vMSN在基因治療和藥物遞送中的巨大潛力，為未來相關技術的開發提供了重要的參考依據。
This study focuses on Astaxanthin and Mivebresib (ABBV-075) due to their unique drug properties and significant therapeutic potential. Astaxanthin, an antioxidant, and Mivebresib, an anticancer drug, despite their different therapeutic purposes and mechanisms, share common challenges in hydrophobicity and drug delivery. Both have low solubility and stability in aqueous environments, leading to poor bioavailability when administered orally. To enhance the bioavailability of hydrophobic drugs in vivo, we employed synthetic mesoporous silica nanoparticles (MSNs). By modifying the surface of MSNs with Triethoxy(octyl)silane (C8-silane), Polyethylene Glycol (PEG), and Trimethyl[3-(trimethoxysilyl)propyl]ammonium Chloride (TA), we created a hydrophobic environment that enhances the loading capacity of hydrophobic drugs and improves their transport in the bloodstream and cellular uptake.
The synthesized C8-MSN-PEG/TA materials were characterized with an average particle size of about 25 nm. Cellular experiments with Astaxanthin showed no toxicity, and C8-MSN-PEG/TA materials exhibited excellent cellular uptake. Flow cytometry antioxidant tests indicated that Astaxanthin carried by C8-MSN-PEG/TA had better antioxidant effects compared to using Astaxanthin alone. Mivebresib, loaded on C8-MSN-PEG/TA, retained its effectiveness in inhibiting cancer cell growth. These results demonstrate that C8-MSN-PEG/TA materials significantly enhance the bioavailability and therapeutic efficacy of hydrophobic drugs.
In the second chapter of this study, we explored the application of virus-like mesoporous silica nanoparticles (vMSNs) as mRNA carriers in animal and cell experiments. First, in animal experiments, we mixed Luc-mRNA, polyethyleneimine (PEI), and vMSN, and performed a single intraperitoneal injection in female mice. The results showed that the vMSN carrier significantly enhanced the therapeutic efficacy of mRNA, displaying stronger fluorescence signals. Subsequently, we conducted in vitro cell treatment experiments. The results demonstrated that mRNA treated with vMSN showed higher therapeutic effects under fluorescence microscopy. Flow cytometry analysis further confirmed that vMSN significantly increased mRNA expression levels in cells. These results indicate that vMSN can effectively carry and protect mRNA, significantly enhancing its therapeutic effects both in vivo and in vitro. This study confirms the significant potential of vMSN in gene therapy and drug delivery, providing important references for the development of related technologies in the future. |
