開發新型產氫奈米載體應用於癌症治療之研究

Abstract

早在 1975 年氫氣被發現具有治療小鼠皮膚麟狀癌的功能後，便揭開了科學家們對氫氣在生物醫學的一系列研究。氫氣的主要功能包括：(1) 中和生物體內活性氧化物(ROS)達到抗氧化的效果，(2) 調控發炎因子以抑制發炎反應，(3) 藉由調節生長因子或細胞凋亡因子以抑制腫瘤的生長。氫氣的給藥方式可分為口服(喝氫水)，吸入(吸氫氣)及注射(氫氣食鹽水)三種，但由於氫氣的分子極小、容易溢散且滯留性差，因此限制了氫氣治療的效果。此外，如何運送氫氣標靶至腫瘤細胞也是亟欲改善的重點。因此，在本研究的目標為開發可以有效治療癌症的新型產氫奈米載體。此奈米載體主要由三項元件組合而成：(1) 以硼烷氨(ammonia borane, AB)為儲氫材料；(2) 中孔奈米矽球(MSN)為藥物載體；(3) 以金奈米粒子催化 AB 產氫的效率。我們的初步實驗成果證實此一載體可以在腫瘤微環境中酸性環境下(pH 6.5〜6.9)增強金奈米粒子催化 AB 的效率，並藉由 MSN 賦予其標靶性，而後因為氫氣可從載體被緩效釋放，增加滯留性，三效合一使該產氫奈米載體可以累積在病灶提供持續性氫氣治療，達到顯著抑制癌細胞生長的效果。

Hydrogen was first reported in 1975 to have therapeutic effects in a skin squamous carcinoma mouse model. The main function of hydrogen as a therapeutic agent was to selectively quench detrimental reactive oxygen species (ROS) resulted in antioxidation. Furthermore, molecular hydrogen was able to regulate inflammatory factors to inhibit the inflammation, and to regulate growth/apoptotic factors to impede tumor growth. The common methods of hydrogen administration include oral route (drinking H2-dissolved water), inhalation (inhaling hydrogen gas), and intravenous injection (injecting H2-dissolved saline); however, the high diffusibility and low solubility of hydrogen often limited the efficacy of hydrogen therapy. Therefore, we believe that a nanomedicine strategy tailors to need by specific disease conditions would be a perfect solution for it. Our nanocarrier is composed of three components: the first is ammonia borane (AB), serving as a hydrogen producer, and the second is mesoporous silica nanoparticle, functioning as a carrier, the third is the gold nanoparticles, participating in speeding up the hydrogen production. Also this carrier is acid-responsive, the tumor microenviroment (TME)-triggered drug release enabled the efficient generation of H2. Preliminary results confirmed that our nanomedicine strategy enhance outcome of hydrogen therapy.