我們建立複合性的上轉換奈米粒子 (UCNPs) 作為藥物載體與精準控制釋放 (remote-control release) 的平台，應用於細胞 (in vitro) 與活體生物 (in vivo) 的螢光標定影像以及腫瘤組織的化學治療。奈米粒子經由表面修飾上葉酸 (FA)後對於細胞膜表面有葉酸抗原過度表現的癌細胞具高親和力。為了提高葉酸在各種癌細胞中的辨認性，我們在葉酸外部接上對於UV光敏感的光罩分子，以連續波二極體近紅外光雷射 (CW diode laser，980 nm)當作開關控制，當上轉換奈米粒子受980nm雷射光激發後，釋放的360 nm紫外光經螢光能量共振轉移使光罩分子斷鍵、脫落並外露具標定作用的葉酸分子，藉由葉酸分子裸露在材料表面與過度表現葉酸受體的癌細胞進行專一性的標定，當材料進入癌細胞內後，以S-S雙硫鍵接在表面的抗癌藥阿黴素DOX進行釋放，將藥物準確的釋放在腫瘤處達到化療效果 (chemotherapy)。因此以多功能性的上轉換奈米粒子作為提高專一性的螢光標定作用且同時達到更有效的治療平台。

In this study, we formulated upconversion nanoparticles (UCNPs) as the NIR-triggered targeting and drug delivery vehicles that successfully delivered in vitro and in vivo to perform near-infrared light photocontrolled targeting, bioimaging, and chemotherapy. To achieve phototargeting, the tumor-homing agent, i.e. folic acid (FA), has been constructed as a photoresponsive molecule. FA has high affinity to folate receptor (FR), where FR is overexpressed on cancer cell surfaces and acted as a tumor marker. However, the number of FR expressed heterogeneously among different cancer cells limiting the tumor delivery capacity of FR endocytosis. Hence, we synthesized FA as the caged folate which was sensitive to UV light illumination. That is NIR light irradiated UCNPs to activate phototargeting with subsequent bioimaging and chemotherapy. For the chemotherapeutic effect, the anti-tumor drug doxorubicin was thiolated on the surface of UCNPs forming disulfide bond that can be cleaved by lysosomal enzymes within the cells. The caged UNCPs can serve as a platform for the improvement of selectively targeting and possible reduction of adverse side effect from chemotherapy.

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