結合化療與放射線療法之大腸直腸癌奈米藥物載體開發

Abstract

大腸直腸癌目前已是全球人類死亡的重大疾病之一，而國內隨著經濟之進步、飲食 習慣之西化，大腸直腸癌之發生率亦隨之增加，且約有三分之一的大腸直腸癌患者 於診斷時即已發生轉移。而本計畫即是利用人類血清白蛋白(Human serum albumin, HSA)分子所帶有的疏水官能基將化療藥物7-乙基-10-羥基喜樹鹼(7-Ethyl- 10-hydroxycamptothecin,SN-38) 包覆於內，並在此藥物載體摻入透明質酸 (Hyaluronic acid, HA)以作為有效標靶大腸直腸癌治療之藥物載體。其中，HSA可 增加此奈米藥物載體於血液中之相容性，有效增加此奈米藥物載體在血液中的半衰 期，而HA則可提高腫瘤與腫瘤幹細胞之標靶效益，提高整體治療效果與降低化療 藥物的毒性。而包覆於奈米藥物載體中的SN-38除了作為化療藥物外，也可作為放 射線療法時之放射增敏劑以有效殺死腫瘤細胞。最後。藉由化療與放射線治療所殺 死的細胞則會更進一步引起自體的免疫反應以攻擊未接受放射線治療之腫瘤病灶或 是轉移的腫瘤細胞，進而提高大腸直腸癌治療之效果。

Colorectal cancer (CRC) is now one of the major diseases in the world. With westernized diet in Taiwan, the incidence of colorectal cancer increases. In about 30% of original colorectal cancer, diagnoses metastasizes has occurred. In this study, the 7-Ethyl-10-hydroxycamptothecin (SN-38) molecules could be loaded in human serum albumin (HSA)-hyaluronic acid (HA) based nanoparticles (SN-38/HSA/HA NPs) by the hydrophobic side groups of amino acid in HSA. Herein, HSA could be used to increase the compatibility and half-life of nanoparticles in the blood, while HA can improve the target benefit to CRC and cancer stem cells (CSCs) and the overall treatment effect and reduce the side effect. In addition to being used as a chemotherapeutic agent, SN-38 in the designed nanoparticles can also be used as a radiosensitizer during radiation therapy to effectively kill tumor cells. At last, cancer cells killed by chemotherapy and radiation will further induce the immune response to attack tumor lesions or metastatic tumor cells without direct radiation exposure. Therefore, the use of this designed nanoparticle could be significantly more efficacious than the chemotherapy alone for colorectal cancer therapy.