以離子電泳法及超音波機械力增強包裹順鉑之幾丁聚醣奈米顆粒於口腔鱗狀細胞癌中之遞送

Abstract

口腔癌為全球常見之癌症之一，目前針對口腔癌的治療，以手術切除作為主要手段。然而治療時常結合放射治療和化學治療以提高治療效果，順鉑（cisplatin）透過與細胞內的DNA交聯，干擾細胞的DNA修復機制促使細胞凋亡，然而強烈的副作用限制其廣泛應用之主要障礙，藥物遞送系統對於化療之進展至為關鍵，在此，我們通過超音波物理力使細胞膜產生聲孔效應，改變細胞膜的通透性來促進藥物的進入以及利用施予外加電場增強帶電藥物分子在皮膚或其他生物屏障中的滲透性之離子電泳法，使藥物能夠精確地釋放至目標位置，從而提高治療的靶向性和療效。通過此二種局部給藥系統，減少藥物導致之全身性副作用，並實現長效、持久的藥物釋放。在此背景下，本實驗於體外試驗及體內試驗中皆證明超音波物理力和離子電泳法增強包裹順鉑藥物之殼聚醣奈米顆粒於口腔鱗狀細胞癌中遞送之有效性，冀望為口腔鱗狀細胞癌化學治療提出了新的可能性方案。

Oral cancer was one of the most common cancers worldwide. At present, the primary treatment for oral cancer was surgical resection. However, the treatment was often combined with radiotherapy and chemotherapy to enhance therapeutic efficacy. Cisplatin was a chemotherapy drug, worked by cross-linking with DNA inside the cell, disrupting the DNA repair mechanisms, and inducing apoptosis. However, its severe side effects were a major barrier to its widespread use. Drug delivery systems were crucial for the advancement of chemotherapy. In this study, ultrasound-induced physical force was used to create sonoporation effect, altering membrane permeability to promote drug entry. Additionally, iontophoresis, an electric field-assisted method, was applied to enhance the penetration of charged drug molecules through the skin or other biological barriers. This allowed for the precise release of drugs to targeted sites, improving the specificity and efficacy of treatment. Through these two local drug delivery systems, systemic side effects of the drugs were minimized, and long-lasting, sustained drug release was achieved. In this context, our in vitro and in vivo experiments demonstrated the effectiveness of ultrasound and iontophoresis-enhanced chitosan nanoparticle-based delivery of cisplatin in oral squamous cell carcinoma. We hoped to provide a new potential approach for chemotherapy in the treatment of oral squamous cell carcinoma.