上轉換奈米粒子與氮化碳量子點複合材料之近紅外光驅動光動力治療

Near-Infrared Light Mediated Photodynamic Therapy Based on Nanocomposite of Upconversion Nanoparticles and Graphitic Carbon Nitride Quantum Dots

李伊容(I-Jung Lee)

指導教授 ： 劉如熹

國立臺灣大學/理學院/化學研究所/碩士(2016年)

https://doi.org/10.6342/NTU201600440

摘要

據近年衛福部統計，惡性腫瘤已多年蟬聯國人死亡率之首，其次為心臟疾病與腦血管疾病，故癌症之預防、診斷與治療已成為目前醫療重大課題之一。現今之癌症治療方法，仍以外科手術切除、化學治療與放射線治療等為主，但治療成效仍有改善空間。
故近年來，人類正積極研究新型輔佐性癌症療法，其中尤以光動力治療備受矚目，因其相較於傳統療法具低侵襲性、低副作用與可選擇性誘導腫瘤壞死之優點 。 本 研 究 主 要 為 合 成 鑭 系 元 素 摻 雜 之 上 轉 換 奈 米 粒 子 (lanthanide-doped upconversion nanoparticles; UCNPs)，並以石墨相氮化碳量子點(graphitic-carbon nitride quantum dots; g-C3N4 )為光感藥物之複合材料應用於近紅外光驅動之光動力治療，其中以高溫共沉澱法製備上轉換奈米粒子，並以鹽酸溶液去除表面配體轉成水相，進一步將聚賴氨酸(poly-L-lysine; PLL)修飾於材料表面使其帶正電，爾後以靜電組裝作用與氮化碳量子點結合。 本研究乃基於上轉換之特殊光學特性，可以連續波近紅外光雷射激發上轉換奈米粒子，將低能量之近紅外光轉換為高能量紫外光與可見光波段之螢光，而其所釋放之紫外光將誘導表面之 g-C3N4 ，於 365 nm 有最佳吸收，並進而釋放出綠色螢光與活性氧分子(reactive oxygen species; ROS)。再者，藉由調控不同濃度之PLL，使最大量之 g-C 3N4 光感藥物承載於上轉換粒子表面，可有效地將氧氣轉換為具細胞毒性之活性氧分子，誘導腫瘤細胞壞死與凋亡，達良好之光動力治療效果。

關鍵字

上轉換奈米粒子 ； 光動力治療

並列摘要

Based on the latest statistics from the Ministry of Health and Welfare, malignant tumor continues to be on top of disease, and then followed by the heart disease and cerebrovascular disease, so the diagnosis and medical treatment has become one of the major issues. Nowadays, cancer treatments still focus on surgical resection, chemotherapy and radiation therapy, but it still can be improved for the more effective treatment.
As a result, human beings have continued to investigate novel adjuvant cancer therapy in recent years, photodynamic therapy (PDT) is now becoming a widely used medical tool. Compared with the traditional therapy, photodynamic therapy is recognized as a minimally invasive procedure, also has little side effect and can selectively lead to tumor necrosis.
The purposes of this research is to fabricate a lanthanide-doped upconversion nanoparticles (UCNPs) nanocomposite by combining with graphitic carbon nitride (g-C 3 N 4 ) photosensitizer for near-infrared (NIR) light mediated PDT application. First, we synthesized upconversion nanoparticles by high temperature co-precipitation method, and then the ligand on the surface were removed via the treatment with hydrochloric acid to obtain water-dispersible nanoparticles. Furthermore, ligand-free upconversion nanoparticles modified with poly-L-lysine (PLL) in order to render the positive-charged group which can allow the attachment of the g-C 3N4 by electrostatic assembling.
Through the excitation of continuous wave NIR laser, upconversion nanoparticles can convert the low-energy NIR light to high energy ultraviolet (UV) or visible light. Owing to this unique optical property of upconversion nanoparticles, the UV light will further photoexcites g-C3N4 at 365 nm, emit the green light and release reaction oxygen species (ROS). Meanwhile, we also modified different concentration of PLL to achieve a moderate condition for high g-C3N4 loading and ensuring maximum energy transfer from UCNPs to g-C3N4 photosensitizer, so as to generate a significant amount of ROS, which can result in tumor cell necrosis and apoptosis for efficient PDT effect.

並列關鍵字

upconversion nanoparticles ； photodynamic therapy

參考文獻

[1] Ineke, M., "Nanotechnology in Europe: Scientific Trends and Organizational Dynamics", Nanotech. 1999, 10, 1.

[2] Gleiter, H., "Nanostructured Materials: Basic Concepts and Microstructure", Acta Mater. 2000, 48, 1.

[3] Isaac, O. J.; Olivia, T.; Julia, L.; Victor, F. P., "Engineered Nonviral Nanocarriers for Intracellular Gene Delivery Applications", Biomed. Mater. 2012, 7, 054106.

[4] Chen, H. M.; Liu, R. S., "Architecture of Metallic Nanostructures: Synthesis Strategy and Specific Applications", J. Phys. Chem. C 2011, 115, 3513.

[5] Baletto, F.; Ferrando, R., "Structural Properties of Nanoclusters: Energetic, Thermodynamic, and Kinetic Effects", Rev. Mod. Phys. 2005, 77, 371.