以C26腫瘤模式探討雙效型微脂體之最適治療條件

Fabricated dual-effect liposome for tumor treatment in C26 tumor-bearing mice

彭柏鈞(Po-Chun Peng)

指導教授 ： 陳進庭

國立臺灣大學/生命科學院/微生物與生化學研究所/碩士(2010年)

https://doi.org/10.6342/NTU.2010.10173

摘要

癌症為現代人類主要的死亡原因之一，目前常使用之治療方式中，將化療藥物包覆於微脂體，形成 Liposomal藥物，雖然能有效降低化療藥物副作用，但也減慢藥物釋放速度，使其療效大幅減弱。而目前新興之癌症治療方式—光動力治療，能針對腫瘤部位，利用光感物質經特定波長光源激發，產生單態氧及自由基對腫瘤細胞進行毒殺。但是在臨床使用時，因為光源穿透力能力影響，對於腫瘤深處組織無法達到有效毒殺效果。因此我們將化療藥物與光感物質包覆於微脂體中，以增加化療藥物的效力，而達到有效毒殺殘存癌細胞之效果。以此種結合光動力治療與化學治療效應之癌症治療模式，提升對於癌症之治療效益。本篇研究以薄膜水合法搭配硫酸銨梯度法建構出粒徑為152.9± 37.7 nm之微脂體。於4℃保存60天後，發現並無明顯藥物滲漏情況，且粒徑也沒有因保存時間延長而改變。而在37℃ PBS環境中，藥物由微脂體中釋放均十分緩慢，顯示此微脂體進入體液後，應該也能穩定將藥物包覆於微脂體中。接著檢測微脂體作用機制，發現經雷射光源照射，激發其中的光感物質產生光動力效應後，能促進化療藥物對癌細胞的毒殺效力。最後檢測微脂體於活體動物體內分佈情況，以及後續的治療成效。

關鍵字

Chlorin e6 ； Doxorubicin ； 光動力治療 ； 雙效型微脂體

並列摘要

Cancer is one of the leading causes of death in modern world. Presently, chemotherapy is an important therapeutic approach for cancer treatment. Chemotherapeutic agent such as doxorubicin has been encapsulated in liposomes which show reduced toxicity. However, the slower rate of drug release significantly reduces the efficacy of cancer therapy. 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. This liposome was developed not only to kill cancer cells using PDT but also to increase the therapeutic effect of chemotherapeutic drug. In this study, the particle size of the constructed liposome was 152.9 ± 37.7 nm. This liposome could be stored at 4℃ for 60 days and showed no significant drug leakage. In vitro PBS environment, drugs released from the liposome were very slow at 37℃, indicating that the formulation in the body fluids should be stable. After light irradiation, PDT was found and the cytotoxic effect of chemotherapeutic drug increases according to the in vitro cell culture system as well as in animal study.

並列關鍵字

Chlorin e6 ； Doxorubicin ； Photodynamic therapy ； Dual-effect liposome

參考文獻

27. 楊育才。2010。開發肺部遞送之吸入性光敏劑微奈米乾粉。台北醫學大學，牙醫學系博士論文。

24. 蔡宜珍。2009。雙效型微脂體用於抑制腫瘤生長之探討。國立台灣大學，微生物與生化學研究所碩士論文。

1. Golubicic I, Borojevic N, Pavlovic T. Risk factors for breast cancer: is ionizing radiation among them? J BUON. 2008. 13:487-494.

2. Stuart-Harris R, Davis A. Optimal adjuvant endocrine therapy for early breast cancer. Womens Health 2010. 6:383-398.

3. Pillis LG, Gu W, Radunskaya AE. Mixed immunotherapy and chemotherapy of tumors: modeling, applications and biological interpretations. J Theor Biol. 2006. 238:841-862.