新穎水性可降解聚胺酯奈米粒包覆超順磁氧化鐵與疏水性藥物之製備與分析

Abstract

傳統超順磁氧化鐵奈米粒(SPIO NPs)具備MRI顯影和過高熱治療的生醫應用，又治療癌症之抗癌藥物為疏水性。本研究使用水性生物可降解聚胺酯的水分散並行自組裝成為奈米粒(PU NPs)之行為，將超順磁氧化鐵奈米粒子或疏水性模擬藥物分別以原位(in situ)混合方式包覆成為超順磁氧化鐵-水性生物可降解聚胺酯奈米粒(SPIO-PU NPs)和藥物-水性生物可降解聚胺酯奈米粒(drug-PU NPs)。先以動態光散射評估包覆結果皆為奈米粒型式。使用穿透式電子顯微鏡、傅立葉紅外線光譜和熱重分析證明SPIO-PU NPs表面為PU高分子，以超導量子磁干涉儀與交流磁場裝置分析其保持原有SPIO超順磁性與磁場加熱功能，同時具備標定癌細胞能力。透過離心超濾法可分析此PU NPs對疏水性藥物具備高包覆效率與藥物釋放，也發現隨著藥物結構中的官能基若與PU預聚合物反應，會產生化學性或物理性之包覆結果並影響藥物釋放能力，而物理性包覆的drug-PU NPs具有良好的藥物釋放行為，進一步得知可經由溫度提高加速藥物釋放。PU NPs無顯著細胞毒性，又藥物之螢光賦予PU NPs具有螢光的能力，依此證明癌細胞亦可攝取PU NPs予以標定。因此本研究PU NPs具有能搭配診斷與雙重治療癌症的潛力。

Superparamagnetic iron oxide nanoparticles (SPIO NPs) are widely used in magnetic resonance imaging and magnetic hyperthermia. In this study, we used the self-assembly behavior of biodegradable polyurethane nanoparticles (PU NPs) in water to encapsulate SPIO NPs (SPIO-PU NPs) or hydrophobic model drugs (drug-PU NPs) by an in-situ method. PU NPs and SPIO-PU NPs were characterized by the dynamic light scattering (DLS), transmission electron microscopy (TEM), infrared spectroscopy (IR), and thermogravimetric analysis (TGA). The superparamagnetic property and magnetic heating ability of SPIO-PU NPs were assessed. PU NPs had no significant cytotoxicity and could be taken up by cells. SPIO-PU NPs were highly efficient in labeling cancer cells with cellular uptake of ~16 pg per cell in average. Hydrophobic drugs were entrapped in PU NPs effectively and showed a sustained release profile. Upon heating, the release of drug was accelerated. This proof-of-concept study demonstrated a novel way to encapsulate SPIO and hydrophobic drug in PU NPs with smart designs for potential applications in cancer diagnostics, hyperthermia, and chemotherapy.