製備高分子包覆之銅/鐵/金複合奈米反應器結合芬頓反應/光動力療法應用於癌症治療

Fabrication of Au-doped Cu/Fe@polymer Nanoreactor with Fenton Reaction/Photodynamic Therapy for Synergetic Cancer Therapy

孫淳凱(Chun-Kai Sun)

指導教授 ： 游佳欣

國立臺灣大學/工學院/化學工程學研究所/碩士(2021年)

https://doi.org/10.6342/NTU202102387

摘要

因為奈米粒子具有微小尺度、多功能與長滯留時間的特性，奈米粒子現今已廣泛應用於生醫領域與癌症治療；在各式奈米粒子中，金屬奈米粒子特殊的表面電漿子共振特性(LSPR)使其更常被研究與應用。鐵(FeNPs)、銅(CuNPs)奈米粒子會透過芬頓反應與類芬頓反應在過量過氧化氫環境中產生氫氧自由基(·OH)；此外，金奈米粒子(AuNPs)搭載光敏劑(PS)，可以吸收光能並轉換成化學能，增強單態氧(1O2)的產生。藉由此二種活性氧化物質(ROS)於腫瘤微環境(TME)的作用，可進一步誘發細胞凋亡。
在此研究中，我們先是透過一步驟水熱反應生成高分子包覆之銅氧化鐵複合奈米粒子(Cu ferrite@PSMA NPs)，再使金離子還原並摻雜於結構中，製成銅鐵金複合奈米反應器(Au/Cu ferrite@PSMA NPs)。產物之金屬比例可以透過調整反應物銅鐵比例與藥品加入順序來控制，而內核-外殼的結構透過穿透式電子顯微鏡(TEM)來驗證。此外，我們證明銅鐵金複合奈米反應器有優異的氫氧自由基與單態氧生成能力；反應器的化學動力與光動力效應在癌細胞中也具有明顯的效果，並可透過磁場來控制癌細胞的胞吞多寡，此結果說明銅鐵金複合奈米反應器具有應用於化學動力與光動力協同治療的潛力。

關鍵字

銅鐵金複合奈米反應器 ； 芬頓反應 ； 活性氧化物質 ； 化學動力治療 ； 光動力治療

並列摘要

Nanoparticle (NP) is currently widely used in biomedical application and cancer treatment due to the minute scale, multi-function, and long retention time. Among the various nanoparticles, the special optical property derived from localized surface plasmon resonance (LSPR) effect of metallic nanoparticles is a primary reason that metallic nanoparticles are researched and applied. Iron (FeNPs) and copper (CuNPs) nanoparticles have the potential to generate hydroxyl radical (·OH) in excess H2O2 via Fenton or Fenton-like reaction. On the other hand, gold nanoparticles (AuNPs) equipped with photosensitizer (PS) can transfer the energy of photons to chemical energy and enhance the production of singlet oxygen (1O2), which is suitable for cancer treatment. With the action of these two reactive oxygen species (ROS) in tumor microenvironment (TME), cell apoptosis can further be induced.
In this work, we first synthesized dual metal nanoparticles (Cu ferrite@PSMA NPs), by a simple one-step hydrothermal reduction reaction; then gold(III) was reduced and doped into the structure, which formed triple metal structure, Au-doped Cu ferrite nanoreactors (Au/Cu ferrite@PSMA NPs). The metal ratio of the product could be controlled by manipulating the Fe/Cu ratio of reactant and the sequence of addition of reactants. The core-shell structure was verified by transmission electron microscopy (TEM). Moreover, the ·OH and 1O2 generation ability of Au/Cu ferrite@PSMA was proved. The chemodynamic and photodynamic effect was measured and the in-vitro ROS generation was obviously observed; furthermore, the behavior of endocytosis by cancer cells can be controlled by the magnetic field. The result indicated that Au/Cu ferrite@PSMA is a potential agent for chemodynamic/photodynamic synergetic therapy.

並列關鍵字

Au-doped Cu ferrite nanoreactors ； Fenton reaction ； reactive oxygen species ； chemodynamic therapy ； photodynamic therapy

參考文獻

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