玻尿酸接枝阿黴素及近紅外光染料作為CD44標靶之奈米載體以結合光熱與化學治療

Abstract

本作將光感藥物IR-780與化療藥物阿黴素(doxorubicin)分別接枝在親水的天然高分子玻尿酸上，形成親疏水兩性的高分子：HA-IR與HA-DOX。藉由親疏水的特性，HA-IR與HA-DOX可形成奈米等級的顆粒，本作中稱為HA-IR/DOX NP。根據不同的HA-IR與HA-DOX比例，HA-IR/DOX NP平均粒徑介於120到170奈米不等，其粒徑具有相對狹窄的分佈。由穩定性測試，此奈米顆粒在保存環境下具有一定的穩定性。由細胞測試，HA-IR/DOX NP可以標靶到CD44過度表現的乳癌細胞MDA-MB-231。而光熱測試則可見HA-IR/DOX NP仍具有光熱升溫的效果。此外HA-IR的螢光，可進行小鼠體內造影。由造影結果顯示HA-IR/DOX NP在尾靜脈注射後會累積至腫瘤。由小鼠抗腫瘤試驗，HA-IR/DOX NP在近紅外光雷射照射下，可達到良好的抗腫瘤效果。

In this study, a photothermal drug, IR-780, and a chemotherapy drug, doxorubicin, were conjugated to hyaluronic acid respectively to form two kinds of amphiphilic polymers, HA-IR and HA-DOX. Based on the amphiphilic property, the HA-IR and HA-DOX mixture can self-assembly to nanoparticles, HA-IR/DOX NP. With different HA-IR/HA-DOX ratios, HA-IR/DOX NPs exhibited particle size from 120 to 170 nm with relatively narrow size distribution. The stability test showed that the HA-IR/DOX NP were stable in 4°C storage condition. From in vitro test, HA-IR/DOX NP targeted to CD44-overexpression cancer cell line, MDA-MB-231. The HA-IR/DOX NP showed photothermal effect and phototoxicity both in vitro and in vivo. On the other hand, the fluorescent property of IR-780 provide a function of in vivo imaging, which shows that the HA-IR/DOX NP accumulated to the tumor via EPR effect and CD44-targeting ligand. The antitumor effect showed that the HA-IR/DOX NP combined the chemo-therapy and the photo-thermal therapy.