探討適體標靶奈米藥物於乳癌治療的成效

Abstract

光動力治療是癌症常用的治療方法之一，其作用原理是透過光照來活化光敏劑，使環境中的氧氣轉換成活性氧化物質(如單線態氧分子)來毒殺癌症細胞。然而其療效會因為腫瘤微環境中的低氧濃度而降低，導致無法完全地根治癌症的病灶。本篇研究是利用在低氧環境下才具有毒殺效果的還原型前驅藥物Tirapazamine (TPZ)與光敏劑Protoporphyrin IX (PpIX)做搭配治療；藉由PpIX的作用，使腫瘤微環境中的氧氣濃度下降，藉此增強低氧還原型前驅藥物的毒殺範圍。 本篇研究的設計是將光敏劑分子修飾在具有良好生物相容性的多孔洞奈米二氧化矽球載體 (Mesoporous silica nanoparticle, MSN) 上，將TPZ裝載於其內，並在多孔奈米二氧化矽球的表面上再修飾對乳癌細胞株 MDA-MB-231具有專一性的DNA適體LXL-1，達到標靶治療的目標。 從本研究的結果中可以發現PpIX與TPZ兩種藥物在各個氧氣壓力下皆能產生協同作用，造成更有效的抗癌效果；帶有LXL-1適體修飾的MSN載體能夠專一性地被MDA-MB-231乳癌細胞吞噬，且兩種藥物裝載於載體內的毒殺效果較兩種藥物以free drug的方式更好，因此這樣複合型的治療策略是能夠有效的毒殺低氧環境下的惡性乳癌細胞。

Photodynamic therapy (PDT) is one of common medical strategies for treating cancer. However, the hypoxic tumor microenvironment often impedes cancer cure rate and increases the likelihood of tumor recurrence. To solve this problem, we attempted to develop a new cancer treatment strategy by combining bioreductive therapy with PDT. It is anticipated that the photosensitizers PpIX will consume most of the oxygen at the tumor site, leading to the generation of singlet oxygen, and concurrently creating a low-oxygen level environment to activate the therapeutic function of bioreductive drug TPZ. Mesoporous silica nanoparticles (MSN) were chosen herein to serve as drug carriers, that were modified with photosensitizer and loaded with bioreductive drugs; in addition, a DNA aptamer LXL-1 was used to functionalize the outer surface of MSN, enabling targeted delivery of therapeutic agents to human breast cancer cell, MDA-MB-231.