結合雙股去氧核醣核酸之磁性氧化鐵-金核殼奈米粒子的合成及特性分析用於可調節藥物釋放系統之研究

Abstract

殼核雙金屬奈米粒子由兩種不同的材質所組成，與單一成分奈米粒子受限於單一性質相比，其更具新穎性及功能性。本篇研究以共沉澱法製備具良好分散性之奈米氧化鐵粒子，隨後以還原法在粒子表面沉積金殼層。並以穿透式電子顯微鏡以及選區電子繞射圖證實氧化鐵-金奈米粒子之核殼結構。此外，由紫外光-可見光吸收光譜以及超導量子干涉儀之量測，可證明氧化鐵-金奈米粒子具有金殼層之光學性質及氧化鐵核之超順磁特性。由於金殼層表面可與修飾有硫基的雙股去氧核醣核酸分子(DNA)作有效結合；同時利用一具有螢光特性的抗癌藥物「小紅莓」，可嵌入經設計的雙股去氧核醣核酸連續且重複的CG鹼基中，形成一創新且多功能的藥物載體。進一步地，將此磁性氧化鐵-金核殼奈米載體置於射頻磁場下，其磁性氧化鐵核因感應磁場而產生熱能，使得對熱敏感的雙股去氧核醣核酸解旋進而在短時間內釋放出藥物小紅莓。而藉由調整射頻磁場開啟的時間，便能調控藥物釋放的量。在本研究中，利用此一藥物釋放系統，在10分鐘內即可達到79%的釋放率。 未來，此載體仍具有巨大發展潛力。金殼層表面可修飾專一性辨識分子的便利性，以及磁性氧化鐵核具有核磁共振顯影能力，加之無論是金或是氧化鐵，都已有文獻指出其高度生物相容性。假以時日，可使此磁性氧化鐵-金核殼奈米粒子的藥物釋放系統成為同時具有顯影能力、標靶治療，並且能調控藥物釋放的完整生醫奈米操作平台。

Magnetic Fe3O4 core/Au shell nanoparticles exhibit both magnetic property of Fe3O4 core and well-established surface chemistry, biological reactivity of Au shell. In this study, magnetic Fe3O4 core/Au shell nanoparticles were synthesized by reducing HAuCl4 on the surface of monodispersed Fe3O4 nanoparticles in the aqueous solution after the facile synthesis of Fe3O4 nanoparticles by co-precipitation process that are more popular for biological applications. Next, transmission electron microscopy (TEM) images, selected-area electron diffraction (SAED) patterns, and optical property by UV-Vis all clearly demonstrate the fact that core/shell nanoparticles were successfully formed as the form of Fe3O4 nanoparticles covered by Au shell; as well as superconducting quantum interference device (SQUID) results show the great superparamagnetic property of Fe3O4 core/Au shell nanoparticles. In addition, by functionalizing the surfaces of magnetic Fe3O4 core/Au shell nanoparticles with CG rich double strand DNA through Au-S bonds, which are themo-sensitive molecules, the doxorubicin with fluorescence as anticancer drug could be carried via intercalation. Further, when the innovative drug carriers were heated under high frequency magnetic field, the double strand DNA dehybridized and then caused the release of doxorubicin. Among suffered different periods of high frequency magnetic field, the release of doxorubicin can be tuned. In this study, the release rate can achieve up to 79% in less than 10 minutes based on our drug delivery system. As a result, this tunable drug delivery system with magnetic Fe3O4 core/Au shell carriers has great promising of developing into multifunctional system including imaging, targeting and tunable drug delivery owing to not only the potential in MR imaging of magnetic core but also well-established surface with adaptive targeting molecules of Au shell, even the proved biocompatibility whether it is Au or Fe3O4 nanoparticle. In the future, a complete bionano platform will be built up.