供生物醫學應用具孔洞金奈米顆粒的製作與特性分析

Abstract

我們結合奈米壓印技術及形成金銀合金技術，再利用硝酸將銀蝕刻的方法製作具孔洞金奈米顆粒。估算孔洞金奈米顆粒的孔洞率可達到大約59%。我們比較不同金銀比例所製作出來的孔洞金奈米顆粒，發現金佔的比例越小，所製作出來的孔洞會比較大，而表面電漿子共振的波長也會隨之藍移。此外，經由感應耦合電漿質譜儀的量測，顯示金銀比例為3:7時所製作出來的孔洞金奈米顆粒所攜帶的光敏劑磺化鋁酞菁之數量最高。由細胞實驗我們得到相同的結果，藉由金銀體積比例為3:7製作出來的金孔洞奈米顆粒攜帶光敏劑進入細胞內後照射波長660 nm 連續波雷射，產生光動力療法顯示出來的細胞死亡區域也是最大。外，我們也比較經由不同退火溫度所製作的奈米顆粒之不同孔洞結構，不同熱退火溫度所製成的金孔洞奈米顆粒有不同的攜帶藥物或光敏劑的能力，特別是當以不同分子量大小的生物連接劑PEG為連接光敏劑及金孔洞奈米顆粒時，一般來說，連接分子量較大的PEG的能力比較差，表示金奈米孔洞顆粒內部的孔洞會限制較大分子量的PEG進入其內部，導致較差的攜帶能力。

We first demonstrate the procedures for fabricating uniform porous gold nanoparticles (PGNPs) based on nano-imprint lithography, Au/Ag alloying, and Ag etching techniques. The porosity of the fabricated PGNP can reach ~59 %. In comparing the results among different samples with different Au/Ag volume ratios in fabrication, a smaller Au/Ag volume ratio leads to larger pores and a shorter localized surface plasmon (LSP) resonance peak wavelength. The inductively coupled plasma mass spectroscopy study provides us with the result that the PGNP fabricated with 3:7 in Au/Ag volume ratio can link with the highest photosensitizer molecule number. In other words, among different PGNP samples, the one fabricated with 3:7 in Au/Ag volume ratio can deliver most photosensitizers into cancer cells for the most efficient photodynamic effect that is also demonstrated in cancer cell damage experiment. We also compare the pore structures of PGNPs fabricated with different annealing temperatures and hence different alloying nanostructures. Among the PGNPs fabricated with the Au/Ag volume ratio fixed at 3:7, the variation of annealing temperature also results in different linkage capabilities, particularly when biolinkers (PEGs) of different molecule weights are used for linking photosensitizer and PGNP. The generally lower linkage capability of PEG of a larger molecule weight indicates that the pores in a PGNP can limit the access of a large molecule.