穀胱甘肽調控之矽金奈米複合載體 於細胞內藥物釋放之應用

Abstract

現今醫學發達，在治療腫瘤或癌症時，經常使用化學療法來達到其治癒目的。而在化學療法的過中，對於系統的載藥量、選擇性與否以及在不同的時間、環境下，可用人為方式順利控制藥物的釋放情形，是當今在化學療法領域中的一大挑戰。抗癌藥物容易對體內臟器產生累積性的傷害而致命，因而限制了藥物的多次使用，故必須發展高度選擇性探針，以便能將化療藥物精確帶到目標細胞位置，減少藥物對人體造成的毒副作用。 本研究開發穀胱甘肽調控之一新穎矽金奈米複合藥物載體 Transferrin-FITC-ReSi-Au NPs，將具有雙硫鍵結的矽材料（ReSi）修飾於金奈米表面，並藉由胺基將模擬藥物異硫氰酸螢光（Fluorescein isothiocyanate, FITC）修飾於藥物載體上，除此之外，更於藥物載體上加入運鐵蛋白（Transferrin protein），其對於人類肝癌細胞（Hep G2）的表面特定的接收器（transferrin receptor）有良好親和性，藉由胞飲作用，藥物載體得以運送進入癌症細胞，致使高濃度的榖胱甘肽還原載體內之雙硫鍵網狀結構，進而在細胞體內誘發藥物釋放，達到標靶治療的目的。

Nanobiotechnology has been recognized as an emerging field with great potential to provide considerably sensitive diagnostics and therapeutics for human diseases. The construction of stimuli-responsive, controlled-release systems for intracellular drug delivery is of crucial importance in practice to improve the healthcare of patients. In this study, we design a glutathione (GSH)-tunable intracellular drug delivery system. The surface of gold nanoparticles (Au NPs, 13-nm) was assembled with a novel silica-based material ReSi (redox-responsive silica), composed by the dithiobis(succinimidyl propionate) and (3-aminopropyl) trimethoxysilane networks. Fluorescein isothiocyanate (FITC) was chosen as a model drug and covalently modified on the surface of ReSi-Au NPs. The disulfide bond in ReSi were sensitive to GSH-gradient (1 mM-10 mM) in cells and the structure could be degraded within 1 hour. Moreover, redox-responsive drug release could be monitored in situ by tracing the sites where fluorescence recovery and Au NPs aggregation occurred due to the destruction of disulfide-bonded networks. We expect such nanoconjugate to serve both as a drug carrier and as an optical probe for cancer theranostics.