以接枝光熱試劑之乙二醇幾丁聚醣為藥物載體在腫瘤治療上之評估

Abstract

在過去的研究中指出生物相容性材料乙二醇幾丁聚醣能用來作為藥物載體。本篇研究利用光熱試劑IR-780修飾上乙二醇幾丁聚醣(glycol chitosan, GC)來形成一個兼具近紅外光影像和光熱化學治療功能的多功能藥物載體。GC-IR能有效的包覆化療藥物SN38形成粒徑200nm左右的奈米粒子SN38@GC-IR/NP。該粒子在給予近紅外光雷射後能升溫產生光熱效應，並且在體溫37℃環境下穩定的釋放藥物。在細胞實驗中，本篇研究使用大腸癌細胞HCT116來作為癌症治療模型。結果顯示SN38@GC-IR/NP的細胞毒性隨著濃度增加而上升，並在結合光熱效應後達到更佳的治療效果。在動物實驗中，SN38@GC-IR/NP經靜脈注射後在血液中的濃度快速下降，並且累積在肝臟和腎臟。推測原因是SN38@GC-IR/NP會被網狀內皮系統(reticuloendothelial system, RES) 辨識並捕捉，以及幾丁聚醣本身有腎臟標靶的性質。總結來說，SN38@GC-IR/NP是一個具有光熱化學治療效果的藥物載體。但是在臨床應用方面，標靶性質和血液中的滯留時間需要進一步的實驗探討。

The biocompatible material, glycol chitosan, was suggested to be used as a drug carrier in previous research. In this study, glycol chitosan was modified with a theranostic agent, IR-780, to achieve a multifunctional drug nano-carrier (GC-IR) for near-infrared (NIR) imaging and chemothermal therapy. GC-IR can encapsulate chemotherapeutic drug SN38 at a high drug loading efficiency and form nanoparticle (SN38@GC-IR/NP) with a diameter around 200nm. SN38@GC-IR/NP presented photothermal effect after NIR laser irradiation and showed sustaining drug release profile under 37℃. Using the colon cancer cell HCT116 as model, in in vitro experiment, SN38@GC-IR/NP showed dose-dependent cytotoxicity and enhanced therapeutic effect in combination with photothermal effect. In in vivo experiment, the concentration of SN38@GC-IR/NP decreased quickly in plasma after intravenous injection and accumulated in kidney and liver. The results were considered to be generated from the capture of reticuloendothelial system (RES) and renal-targeting characteristics of chitosan. In sum, SN38@GC-IR/NP was proved to be a drug nano-carrier with chemothermal therapeutic effect. However, further exploration on targeting property and retention time of the nanoparticle is necessary for clinical uses.