雙效型微脂體用於抑制腫瘤生長之探討

Abstract

癌症是由細胞不正常複製、增生，所形成的惡性腫瘤組織，會入侵並破壞正常組織器官，甚至轉移至身體其他部位，導致患者死亡。目前常使用之化學治療方式，因無法只針對癌細胞進行專一毒殺，使用上會對患者造成副作用。所以科學家利用微脂體 (liposome) 能專一累積於腫瘤組織之特性，將化療藥物包覆其中，藉此改善化療藥物毒性；但由於包覆於微脂體中，但由於藥物釋放速度過慢，而使微脂體化療藥物治療癌症效果不如預期。而近期一種癌症治療方式—光動力治療，則是針對腫瘤部位，利用光感物質被特定波長光源激發，產生單態氧及自由基，造成腫瘤細胞死亡之治療模式。本篇研究即是想結合光動力治療及化學治療兩種方式，結合包在埋微脂體中的光感物質與化療藥物，以造成腫瘤毒殺外，達到加強腫瘤毒殺效果。本研究首先在細胞實驗中，確認微脂體藥物，有更好之細胞毒殺效果。而後在活體老鼠實驗中也發現，兩者之結合具有更好之抑制腫瘤生長效應，並延長老鼠之存活時間。

Photodynamic therapy (PDT), which is based on the uptake of a photosensitizer followed by the selective irradiation of light, is a therapeutic modality for cancer treatment. Due to the limited light penetration, PDT is generally considered as a local treatment. To enhance the efficacy of cancer treatment, we prepared a polyethylene glycol (PEG) modified liposome simultaneously encapsulated with photosensitizer or chemotherapeutical drug. The cellular localization of these liposomes was in the cytoplasmic area only. To address the cytotoxicity of these liposomes, colony formation assay was performed after light irradiation. At the light dose of 20 J/cm2, 5 ng/ml of liposome drug can produce 40% cytotoxicity; however, the combined effect of liposome can produce over 80% cytotoxicity. Finally, we examined the anti-tumor efficacy of the liposome with C-26 syngeneic tumor model in BALB/cByJ mice