發展具磁振造影與光熱及光動力治療之多功能奈米團, 探討以NBD衍生物為配位基之Roussin’s Red Esters在細胞內的分布狀態

Abstract

本研究以奈米金桿結合超順磁氧化鐵奈米粒子發展新式之癌症診斷及治療雙功能奈米團平台。此奈米團具備高度穩定性，在高溫加熱及強磁場環境中仍可維持奈米團之分散性。此平台藉由聚集多顆超順磁氧化鐵奈米粒子於奈米團中，大幅增強超順磁氧化鐵奈米粒子之磁振造影能力，與原先超順磁氧化鐵奈米粒子和市售T2 對比劑Resovist相比，其T2 對比訊號增強1.9 倍和2.2 倍。透過Herceptin 抗體修飾後之奈米團平台於小動物模組實驗中亦證實具高度辨識能力，其針對Her-2/neu 受體高表現之腫瘤觀測到- 70.4 ± 4.3%之訊號變弱。此外，此奈米團可吸收808 nm 波長的近紅外光並將其能量轉換為熱能而達到局部升溫效果，其在水溶液中可升溫至約50 °C，在細胞實驗中奈米團成功地毒殺癌細胞；在小動物模組實驗也證明對於腫瘤有絕佳治療效果。另一方面此奈米團在947 nm的雷射刺激下可偵測到單重態氧發出1268 nm波長的磷光，結果表示奈米團具有產生單重態氧的能力。故此奈米團可應用於磁振造影，在光熱及光動力療法的開發上也相當具潛力，期待未來可開發成為一新式診斷治療平台以應臨床檢測與癌症治療的需求。

In this study, a novel dual functional theranosis platform is developed based on gold nanorods (AuNRs) and manganese magnetism-engineered iron oxide (MnMEIO) to combine diagnosis and therapy in one nanocluster. The platform showed improved T2-weighted MR imaging and exhibited a near-infrared (NIR) induced temperature elevation due to the unique characteristics of AuNRs@MnMEIOs nanoclusters. The AuNRs@MnMEIOs nanoclusters also demonstrated a 1.9 and 2.2- fold r2 relaxivity value higher than those of monodispersed MnMEIO and Resovist. In addition, in vivo MR imaging study found that the contrast enhancements were - 70.4 ± 4.3% versus - 7.5 ± 3.0% in Her-2/neu overexpression tumors as compared to the control tumors. More importantly, NIR laser irradiation to the tumor site resulted in outstanding photothermal therapeutic efficacy. Besides, the characteristic singlet oxygen phosphorescence emission at roughly 1268 nm of nanocluster was detected under the 947 nm wavelength laser irradiation. This result showing that AuNRs@MnMEIOs nanoclusters are capable of generating singlet oxygen. Therefore, such nanoclusters can be developed as a promising nanosystem for effective cancer diagnosis and therapy.