具抗氧化與促氧化活性之碳量子點應用於光動力及細胞保護效應

Photodynamic and Cytoprotective Effects of Carbon Dots with Pro- and Anti-oxidant Activities

郭采蓁(Tsai-Jhen Kuo)

指導教授 ： 張煥宗

國立臺灣大學/理學院/化學研究所/碩士(2021年)

https://doi.org/10.6342/NTU202200006

摘要

碳點 (Carbon dots, C-dots) 具有出色的發光特性與高度生物相容性，在醫學應用如生物顯影、藥物傳遞、醫學診斷與新型治療劑擁有廣闊的前景。對於這些應用，深入了解碳點的特性如何與生物系統相互作用是至關重要的。於本研究中，以對苯二胺 (pPD)、3,5-二羥基苯甲酸 (DHBA) 與β-環糊精 (β-CD) 作為前驅物合成碳點 (β-DP)。藉由調控光照射條件，分別驗證β-DP的促氧化及抗氧化活性。透過535 nm綠光雷射照射，以9,10-蒽基-雙(亞甲基)二丙二酸 (ABDA) 試驗測定β-DP產生單線態氧 (Singlet oxygen, 1O2) 之量子產率為7.2%，並且能夠藉由提升細胞內活性氧物質 (ROS) 水平，使其照光後產生的氫氧自由基與單線態氧等活性氧物質表現光活性，有效抑制MCF-7細胞存活率小於20%。此外，β-DP同時亦具備清除含氮自由基及氫氧自由基的能力，並且能夠協助MCF-10A細胞抵禦外源性的氧化壓力損傷。這些理想的特性，說明可藉由光調控具備促氧化與抗氧化雙重活性的β-DP對於癌症治療的安全應用，擁有相當大的發展潛能。

關鍵字

碳點 ； 促氧化劑 ； 抗氧化劑 ； 光動力 ； 細胞保護作用

並列摘要

Carbon dots (C-dots), promising luminescent nanomaterials with exceptional physicochemical properties, show great potential for medical applications such as bio-imaging, drug delivery, diagnosis, and novel therapeutics. Understanding the interaction of C-dots with biological systems is essential for these applications. In this thesis, C-dots were synthesized through a hydrothermal method using p-phenylenediamine (pPD), 3,5-dihydroxylbenzoic acid (DHBA), and β-cyclodextrin (β-CD) as precursors. The as-prepared β-DP C-dots exhibit an excellent anti-oxidant activity to effectively scavenge free radicals, including hydroxyl radical, superoxide, and DPPH. By applying a 535 nm laser, β-DP C-dots produce singlet oxygen with a quantum yield (1O2) of 7.2%. Attributing to the boost generation of reactive oxygen species (ROS) such as hydroxyl radical and singlet oxygen upon 530 nm laser irradiation, β-DP C-dots were successfully applied for photodynamic therapy against breast cancer cells via perturbing their intracellular ROS and antioxidant balance. In addition, the β-DP C-dots can efficiently scavenge free radicals to protect normal cells from exogenous oxidative stress. Having the pro- and anti-oxidant dual activities, β-DP C-dots hold potential as an anticancer drug upon laser irradiation at 535 nm.

並列關鍵字

carbon dots ； pro-oxidant ； anti-oxidant ； photodynamic ； cytoprotective effect

參考文獻

[1] Ross, J. S.; Schenkein, D. P.; Pietrusko, R.; Rolfe, M.; Linette, G. P.; Stec, J.; Stagliano, N. E.; Ginsburg, G. S.; Symmans, W. F.; Pusztai, L.; Hortobagyi, G. N. ‘‘Targeted Therapies for Cancer 2004’’ Am. J. Clin. Pathol. 2004, 122, 598–609.

[2] Jia, Q.; Ge, J.; Liu, W.; Zheng, X.; Chen, S.; Wen, Y.; Zhang, H.; Wang, P. ‘‘A Magnetofluorescent Carbon Dot Assembly as an Acidic H2O2-Driven Oxygenerator to Regulate Tumor Hypoxia for Simultaneous Bimodal Imaging and Enhanced Photodynamic Therapy’’ Adv. Mater. 2018, 30, 1706090.

[3] Wang, Y.; Dong, Z.; Hu, H.; Yang, Q.; Hou, X.; Wu, P. ‘‘DNA-Modulated Photosensitization: Current Status and Future Aspects in Biosensing and Environmental Monitoring’’ Analytical and Bioanalytical Chemistry 2019, 411, 4415–4423.

[4] Fan, W.; Yung, B.; Huang, P.; Chen, X. ‘‘Nanotechnology for Multimodal Synergistic Cancer Therapy’’ Chem. Rev. 2017, 117, 13566–13638.

[5] Wang, J.; Yi, J. ‘‘Cancer Cell Killing via ROS: To Increase or Decrease, That is the Question’’ Cancer Biology Therapy 2008, 12, 1875–1884.