製備溫感性奈米微胞載體針對癌症做藥物傳輸及光熱治療

Abstract

惡性腫瘤已蟬聯國人十大死因之首數年，而大腸癌位於惡性腫瘤好發率之前三名，治療的重要性不言而喻。為了體現更良好的大腸癌治療，奈米級高分子載體被廣泛運用在藥物傳輸系統來治療癌症，利用雙親性高分子包覆光感藥物或化療藥物,進行癌細胞毒殺並減少藥物對正常細胞之毒性與副作用產生。然而現今之藥物載體並非僅應用於化學治療，光動力治療與光熱燒灼等也於近年來蓬勃發展。藥物使用奈米載體搭載之優點為，可利用其包覆藥物減低非作用目標之細胞攝取，再者，奈米級載體可藉由其粒徑極小之特性產生增強通透性與延遲效應(EPR effects)進而達成在腫瘤組織之被動標靶(passive targeting)的特性，增強藥物累積量與減少藥物之使用量。除此之外，利用雷射去針對病灶作熱燒灼治療，對於某些特定淺層疾病具有良好的治癒效果，合併光熱燒灼與化學治療於癌症治癒上可以達到加成效應也為現今熱門研究的課題。將光感藥物及化療藥物同時包埋於奈米藥物載體內部，形成多功能之藥物載體，能同時針對腫瘤作藥物傳輸及光熱燒灼的雙重效果。 本篇研究利用熱敏感性之高分子p(NIPAAM-co-PEGMEA)-b-PCL製備奈米微胞載體，利用疏水核心包覆化療藥物17-AAG及光敏藥物IR-780 iodide，成為同時具有化學治療與光熱燒灼能力之多功能型奈米藥物，並且可利用光熱燒灼的溫度變化達到控制藥物釋放的效果。在物理性質方面，粒徑大小位於170 nm左右，兩種藥物包覆率可同時達到近35%。在臨界微胞濃度值方面,表現出此奈米載體在大量稀釋環境中穩定性甚佳。此外，在細胞毒性與動物實驗等觀察，可發現結合光熱燒灼與化學治療較單一藥物治療有著較佳之治療效果及具有協同作用(synergism)，為一高潛力之多功能奈米藥物，並期望本研究能對生物醫學領域稍具貢獻。

Until now, cancer has been the top causes of death. Among all different types of cancers, colorectal cancer is the most common type. As a result, anti-cancer therapies against colorectal cancers are very important. Polymeric nanoparticles have already been widely used in the research field of drug delivery systems. For instance, amphiphilic micelles could be designed to encapsulate hydrophobic anticancer agents or photosensitizers, to reduce cytotoxicities and side effects to normal cells during treatment. So far, researched in anti-cancer therapy not only include better drug delivery systems but better photodynamic therapy and photothermal ablation therapy modalities. There are many advantages for nano-carriers such as that nano-sized vectors could induce enhanced permeability and retention (EPR) effects in tumor cells. The passive targeting could cause higher drug accumulations at tumor sites while decreasing the amount of anticancer agents used. In this study, thermo-sensitive polymers, p(NIPAAM-co-PEGMEA)-b-PCL, were synthesized and developed as nano-micelle. Hydrophobic anticancer agents, 17-AAG and photosensitizer IR-780 iodide, were loaded in the core of micelles both chemo-therapies and photothermal ablation therapies were reached simultaneously using this new micelle. The release of the micelle could be controlled by temperature variation. Regarding to the physical and chemical properties, its sizes was about 170 nm, the drug encapsulated efficiency would approximately 35 %. The critical micelles concentrations (CMC) were all small enough to allow the micelle to be stable in dilutions. From the data of cell viabilities and animal experiments, the combination treatment of photothermal ablation and chemo-therapy had more treatment efficacy and synergistic effect than treatments using single drugs. Overall, the micelle developed here would hopefully help in the field of biomedical engineering.