具癌細胞標靶及高水溶性的Fe3O4奈米鐵粒子製備

本研究中，利用聚丙烯酸(ployacrylic acid, PAA)來修飾的四氧化三鐵(Fe3O4 , IO)能夠使其奈米粒子能分散在水中。PAA之所以能讓粒子穩定在水中分散，是PAA這個聚電解質的羧酸根離子(COO-)能將IO粒子螯合起來，而暴露在外層的COO-可以與具有癌細胞標靶的葉酸(folic acid, FA)分子反應，利用聚乙二醇(polyethylene glycol, PEG)當間聯劑，形成最終產物(PAAIO-Rh-FA)。由於PEG可以增加PAA修飾的奈米鐵粒子在血液中的循環及避免巨噬細胞的吞噬功能， PAAIO-Rh-FA中超順磁性的奈米鐵，可使其作為磁振造影追蹤劑；若是再利用化學反應方式接掛螢光分子或是療效藥物分子在表面上，使其具備多功能特性，將來在生物醫學上可以被廣泛應用。因此，本實驗首先合成出及分析所設計的多功能性的PAAIO-Rh-FA，再對SPION及其衍生物做毒性的測試，發現它們在KB細胞有良好的細胞存活率，並利用流式細胞儀與共軛焦顯微鏡來觀察接掛Rhodamine 123的PAAIO-Rh和PAAIO-Rh-FA在KB細胞內部活動的情形。由實驗結果發現PAAIO-Rh-FA會與細胞的葉酸受器結合，使其較容易進入細胞之中。而在MRI影像中，發現PAAIO-Rh-FA的訊號下降要比PAAIO-Rh來的明顯。

關鍵字

四氧化三鐵；聚丙烯酸；葉酸受器；超順磁性； MRI影像

並列摘要

In this study, we modify iron oxide with poly (acrylic acid) (PAA, MW=2K Da) in order to obtain a water-soluble iron oxide. Indeed, the superior water solubility is achieved after using PAA as a capping agent, the carboxylate groups of which partially bind to the iron nanocrystal surface and partially extend into the surrounding water. Then, superparamagnetic iron oxide nanoparticle (SPION) is chelated by PAA, which is further conjugated with folic acid (FA) using polyethylene glycol (PEG) as a spacer. The monodisperse, highly water-soluble, superparamagnetic, and biocompatible magnetite nanocrystals endow versatile biomedical applications. The cell viability of PAAIO in KB cells exhibits nontoxic. The cellular internalization of PAAIO-Rh and PAAIO-Rh-FA into KB cells is observed by flow-cytometric analysis and confocal laser scanning microscopy. The preliminary results demonstrate that PAAIO-Rh-FA have the ability to target folate receptor. In MR image, the signal of PAAIO-Rh-FA show significant decreased than the signal of PAAIO-Rh in high iron concentration.