中孔洞氧化矽奈米粒子的修飾及生物醫學上之應用

Abstract

中孔洞氧化矽奈米材料具有高表面積、大孔體積、均勻孔徑大小、表面容易修飾以及生物相容性佳等優點；因此在本研究中，我們以中孔洞氧化矽奈米材料作為主軸，依其結構與生醫應用上不同分成兩個主題。 第一部分我們成功利用共價修飾的方法，發展出具有螢光及釓金屬順磁性質的多功能氧化矽奈米複合材料(Gd(OH)3-FITC@MSN）；此多功能中孔洞氧化矽材料具有高弛緩率（relaxivity）及穩定螢光等性質，並可藉細胞吞噬作用成功進入細胞內且對於細胞只存有極低的生物毒性。更重要的是Gd(OH)3-FITC@MSN材料相較臨床使用的核磁共振顯影劑有更好的影像對比效果，再加上螢光光學及中孔洞材料等特點，此材料在未來影像追蹤以及藥物釋放等應用上有很大的潛力。 第二部份我們系統性地探討聚乙二醇分子（polyethylene glycol, PEG）的分子量及表面修飾密度對中孔洞氧化矽奈米材料的影響。我們找到最適合的聚乙二醇修飾條件，使中孔洞氧化矽奈米粒子在模擬生理條件的培養液中有最佳的粒子穩定性且可以成功降低小鼠巨噬細胞（RAW 264.7）的非專一性吞噬，並進而避開身體內的網狀內皮系統（reticuloendothelial system, RES），對於提升生物體內專一性標定及藥物輸送的效率有很大的幫助。

Mesoporous silica nanoparticles (MSNs) are emerging as promising candidates in using these materials for biomedical applications because of the unique characteristics, including high surface area, uniform pore size, easy modification and great biocompatibility. In first part, we have successfully developed two kinds of materials base on mesoporous silica nanoparticles (MSN) for biomedical applications. The first part shows the synthesis and characterization of a multifunctional nanomaterial, Gd(OH)3-FITC@MSN, possessing magnetic, fluorescent and porous properties. Its utility for both magnetic resonance and optical imaging was clearly demonstrated in vitro. The result shows Gd(OH)3-FITC@MSN performed well for cellular magnetic resonance imaging (MRI) even at high magnetic field (7T), indicating it could be a promising T1 or T2 contrast agent. The second part presents a systematic study of 50 nm MSN modified with PEG of different molecular weights and surface chain density. The results show that, as the surface of MSN mostly covered by PEG with molecular weight of 30 kDa, the PEGylated MSN could stably suspend in cell-culture medium and physiology environments without agglomeration and obvious size changes even incubated for two weeks. Besides, MSNs conjugated with PEG chains effectively reduce non-specific uptake of RAW 264.7 macrophage cells indicating these particles could escape from the innate immune system which is critical for efficient target-specific delivery.