Rapid microwave-assisted synthesis of heteroatom-doped carbon quantum dot for tumor-targeted bioimaging and anticancer drug delivery applications

• Main Authors: Sheng-Hui Chiu, 邱勝暉
• Other Authors: Jia-Yaw Chang
• Format: Others
• Language: zh-TW
• Published: 2016
• Online Access: http://ndltd.ncl.edu.tw/handle/21279859491629145651

碩士 === 國立臺灣科技大學 === 化學工程系 === 104 === Carbon quantum dot (CQD) exhibits unique properties such as tunable fluorescence, high photostability, chemical inertness, low toxicity, and biocompatibility, which are beneficial for bioimaging application. Herein, we synthesized heteroatom doped CQD by using a one-pot microwave method. Doping heteroatom elements into CQD could modulate the fluorescent properties and improve the functionality. Part Ⅰ Sulphur (S), boron (B), and phosphorous (P) heteroatom doped CQD (S-CQD, B-CQD, and P-CQD) were synthesized within 10 min by using a one-pot microwave method. Doping S, B, and P heteroatom into CQD could increase the quantum yield from 5.9% to 22.5, 24.9, and 51.7%, respectively. P-CQD was conjugated with hyaluronic acid forming P-CQD-HA for targeting fluorescence imaging. The in vitro and in vivo studies confirmed the high biocompatibility and low toxicity of P-CQD-HA. The targeting capabilities of P-CQD-HA were confirmed in B16F1 and HeLa cells using in vitro fluorescence imaging. Additionally, we successfully demonstrated in vivo fluorescence imaging of the P-CQD-HA, using zebrafish as an animal model. Part Ⅱ Gadolinium (Gd) heteroatom doped CQD (GdCQD) was synthesized within 10 min by using a one-pot microwave method. Our results showed that the synthesized multifunctional GdCQD has excellent structural, fluorescent, and magnetic properties. GdCQD enhanced the MR response as compared to that for commercial Gd-DTPA. The multifunctional GdCQD was conjugated with folic acid forming GdCQD-FA for targeting dual modal fluorescence/magnetic resonance (MR) imaging. The in vitro and in vivo studies confirmed the high biocompatibility and low toxicity of GdCQD-FA. The targeting capabilities of GdCQD-FA were confirmed in HeLa and HePG2 cells using in vitro fluorescence and MR dual modality imaging. We successfully demonstrated in vivo fluorescence imaging of the GdCQD-FA, using zebrafish as an animal model. Additionally, an anticancer drug, doxorubicin (DOX), was incorporated into the nanocomposite forming GdCQD-FA/DOX, which enables targeted drug delivery. Importantly, the prepared multifunctional GdCQD-FA/DOX showed a high quantity of DOX loading capacity (about 75%) and pH-sensitive drug release. The uptake into cancer cells and the intracellular location of the GdCQD-FA/DOX were observed by confocal laser scanning microscopy. Therefore, the GdCQD-FA/DOX nanocomposite is a promising strategy for potential application as a dual modal diagnosis agent and drug delivery system for chemotherapy.