應用磁振造影與光熱治療之雙功能奈米團結合極化巨噬細胞建立抗腫瘤特洛伊木馬

Abstract

本研究使用了奈米金桿與超順磁氧化鐵奈米粒子之雙功能奈米團，試圖利用極化巨噬細胞作為奈米團之載體，讓奈米團被巨噬細胞攜帶並累積在腫瘤處，再藉由奈米團之診斷及治療效果對抗腫瘤細胞。此奈米團具備高度膠體穩定性，在靜置達20星期後，其奈米團大小與表面電性皆能夠維持在56 nm與 -6 mV左右，且不同於市售的奈米金桿無法重複升溫，本研究所合成的奈米團能夠反覆升溫至72 ºC，具有相當好的重複升溫穩定性，且其橫向弛緩率高於市售之MRI-T2顯影對比劑Resovist 之橫向弛緩率2.25倍，證明它的確是一個理想的診斷治療工具。在體外試驗方面，本研究成功以不同刺激物誘導出M1及M2-巨噬細胞，且在利用奈米團進行標定後，M1-巨噬細胞內的鐵含量能達到32.8 pg/cell，顯示奈米團能進行細胞標定，另外，由體外熱殺能力試驗可證實奈米團的升溫能力不單會影響其所在的細胞，也會影響周圍的細胞甚至造成周圍細胞的死亡。諸多實驗結果證明以巨噬細胞為載體建立抗腫瘤特洛伊木馬的策略是確有其應用潛力的。

In this study, a novel anti-tumor Trojan horse was constructed by the dual functional gold nanorods (AuNRs)@magnetism- engineered iron oxides (MnMEIOs) nanocluster and polarized macrophages. This nanocluster have excellent colloidal stability. During 20 weeks, nanocluster maintain the size at 56 nm and zeta potential at -6 mV. Futhermore, unlike commercial gold nanorods, our nanocluster showed good repeated heating stability by repeated heating to 72 ºC. In the other hand, the r2 relaxivity of nanocluster is 2.25 fold higher than commercial T2-weighted MR contrast agent, Resovist, making nanocluster a ideal tool to diagnosis and therapy. In our in vitro experiments, we successfully polarized macrophages into M1 and M2 phase by different stimulus. In the following cell labeling assay, nanocluster showed good labeling ability by accumulate 32.8 pg of iron/cell inside M1-macrophages. In photothermal therapy experiment, nanocluster showed its photothermal therapy ability can't limited by host cell. All of the results showed that combine nanocluster and polarized macrophage as a Trojan horse is a promising stradgy against tumor.