電荷組裝之矽奈米複合材料於癌細胞標靶光動力學治療之應用

現今醫學發達，在治療癌症經常使用化學藥物療法，但化學治療在現階段臨床醫療上不僅會非專一性的損傷正常的健康細胞，也無法完全有效地根除腫瘤。光動力治療法 (photodynamic therapy, PDT) 是一種非侵入性的治療癌症方式，其機制是利用特定波長的光將光敏感劑 (photosensitizer) 激發後，產生活性氧化物質 (Reactive oxygen species)，例如單態氧 (Singlet oxygen) 使其對癌細胞造成破壞，達到治療效果。然而，許多的光敏感劑由於疏水、本身的非專一性仍會對正常細胞造成傷害以及在生物體環境中易遭到降解等諸多限制，造成在光動力治療上的療效不佳。本研究藉由電荷組裝開發一矽奈米複合藥物載體 Apt-MB-Si NPs，將對於MUC1 (於癌細胞中高度表現) 蛋白具高度親和性的適體 (Aptamer) 修飾於矽奈米粒子表面，並藉由電荷吸附將親水性的光敏感劑─亞甲藍 (Methylene blue) 乘載於適體上以進行標靶藥物投遞的目的。我們發現藉由此矽奈米複合材料，不僅成功降低光敏感劑的用量，也大幅降低投藥時間，進而達成癌細胞標靶光動力治療的效果。

關鍵字

矽奈米複合材料；亞甲藍； MUC1適體；電荷組裝；光動力治療

並列摘要

Conventional cancer treatments have many limitations which often fail to completely eradicate the tumor and cause damages to normal cells. Photodynamic therapy (PDT), by the excitation of photosensitizers with light to generate reactive oxygen species (ROSs) such as 1O2, has emerged as a noninvasive technique for cancer theranostics. However, the clinical use of many photosensitizers has been challenged by their nonspecific damage to normal tissues, environmental degradation and hydrophobicity...etc. To overcome the existing limitation and to enhance the selectivity of photodynamic therapy, we developed a simple electrostatic adsorption strategy to fabricate silica nanocomposite (Apt-MB-Si NPs) by sequentially functionalizing MUC1 aptamer for tumor targeting and hydrophilic photosensitizer methylene blue (MB) for the PDT application. We found effective generation of singlet oxygen could be achieved with low PS dosage and short irradiation time by current strategy.

並列關鍵字

silica nanocomposite ； methylene blue ； MUC1 aptamer ； electrostatic assembly ； photodynamic therapy (PDT)

參考文獻

1. Sahu, A.; Choi, W. I.; Lee, J. H.; Tae, G., Graphene oxide mediated delivery of methylene blue for combined photodynamic and photothermal therapy. Biomaterials 2013, 34 (26), 6239-6248.

2. Khdair, A.; Handa, H.; Mao, G.; Panyam, J., Nanoparticle-mediated combination chemotherapy and photodynamic therapy overcomes tumor drug resistance< i> in vitro. European Journal of Pharmaceutics and Biopharmaceutics 2009, 71 (2), 214-222.

4. Oleinick, N. L.; Morris, R. L.; Belichenko, I., The role of apoptosis in response to photodynamic therapy: what, where, why, and how. Photochemical & Photobiological Sciences 2002, 1 (1), 1-21.

6. Allison, R. R.; Downie, G. H.; Cuenca, R.; Hu, X.-H.; Childs, C. J. H.; Sibata, C. H., Photosensitizers in clinical PDT. Photodiagnosis and Photodynamic Therapy 2004, 1 (1), 27-42.

8. Redmond, R. W.; Gamlin, J. N., A compilation of singlet oxygen yields from biologically relevant molecules. Photochemistry and photobiology 1999, 70 (4), 391-475.

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電荷組裝之矽奈米複合材料於癌細胞標靶光動力學治療之應用

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