研究生: |
蕭建華 CHIEN-HUA HSIAO |
---|---|
論文名稱: |
活性氧響應性藥物結合光動力效果碳點之合成與生醫應用 Synthesis of photodynamic carbon dots integrated with ROS-responsive drug and their biomedical application |
指導教授: |
張家耀
JIA-YAW CHANG |
口試委員: |
何郡軒
JINN-HSUAN HO 張榮善 JUNG-SHAN CHANG |
學位類別: |
碩士 Master |
系所名稱: |
工程學院 - 化學工程系 Department of Chemical Engineering |
論文出版年: | 2022 |
畢業學年度: | 110 |
語文別: | 中文 |
論文頁數: | 107 |
中文關鍵詞: | 碳點 、藥物傳輸系統 、異原子摻雜 、酸氧化處理 、生醫應用 |
外文關鍵詞: | Carbon dots, drug delivery system, heteratom doping, acid oxidation treatment, biomedical application |
相關次數: | 點閱:230 下載:0 |
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本研究以碳點(Carbon dots, CDs)設計具生物相容性之水溶性藥物載體奈米複合物(CPT-N,S,Cl@CDs),因其具有低毒性及具豐富易改質官能基團之特性。首先,選用微波輔助技術合成法,以對苯二胺搭配過氯酸、L-cystine及L-selenocystine製備碳點,大幅提升螢光量子產率。其中以對苯二胺作為碳源,過氯酸當作鈍化劑改善表面缺陷,而L-cystine及L-selenocystine則以異原子摻雜法提升螢光性質,製備出N,Se,Cl@CDs及N,S,Cl@CDs,並使用UV-Vis、PL、XPS、FTIR及Raman分析螢光性質、材料結構及鍵結組成。
隨後對N,Se,Cl@CDs及N,S,Cl@CDs進行光動力比較,選用光動力效果較佳之N,S,Cl@CDs,透過交聯反應結合活性氧(ROS)響應性抗癌藥物(TL-CPT)形成CPT-N,S,Cl@CDs。若使用雷射照射CPT-N,S,Cl@CDs,產生之ROS不僅能殺傷癌細胞,也能破壞ROS響應硫醇鍵釋放CPT,達到雙重治療效果;而經由藥物釋放模擬,透過改變材料前處理條件,驗證其藥物釋放可控性。
於體外細胞生物應用,透過細胞攝取及毒性測試,驗證CPT-N,S,Cl@CDs具優異生物相容性;於雷射照射下,因材料具光動力-藥物治療效果,癌症細胞致死率大幅提升。而藉由細胞顯影及染色試驗,證實材料於體外細胞仍具活性,擁有產生ROS及有效殺死癌細胞之能力。
Herein, a biocompatible and water-soluble drug carrier agent was designed using carbon dot (CDs) due to it’s low toxicity and abundant surface functional group. Firstly, by employing p-phenylenediamine as the carbon source we have synthesized red-emissive CDs via microwave-assisted technique. The optical properties of CDs was improved by using surface passivating agent such as perchloric acid, resulting N,Cl@CDs which significantly improved the fluorescence quantum yield. Moreover, selenium and sulfur were separately doped into the carbon dots structure, and the fluorescence properties were further improved by heteroatom doping method to prepare N,Se,Cl@CDs and N,S,Cl@CDs, and use UV-Vis, PL, XPS, FTIR, and Raman analysis of fluorescence properties, material structure, and bonding composition.
The photodynamic effect of N,Se,Cl@CDs and N,S,Cl@CDs was then compared, and the N,S,Cl@CDs with the better photodynamic effect was chosen to combine ROS responsive anticancer drug(TL-CPT) through cross-linking reaction(CPT-N,S,Cl@CDs). When CPT-N,S,Cl@CDs is laser-irradiated, the ROS produced not only kills cancer cells, but also destroys ROS responsive thiol bonds to release CPT, resulting in a dual therapeutic effect. The controllability of drug release was verified using drug release simulation by changing the material's pretreatment conditions.
In vitro cell biological application, through cell uptake and toxicity tests, it is confirmed that CPT-N,S,Cl@CDs has excellent biocompatibility; under laser irradiation, the lethality of cancer cells is greatly improved due to the material's photodynamic-drug treatment effect. Cell imaging capability and staining tests confirmed that the material was still active in vitro, capable of generating ROS and effectively killing cancer cells.
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