奈米抗癌藥物結合超音波搭配微氣泡對小鼠耳朵腫瘤之生長影響

Abstract

本研究利用小鼠耳朵腫瘤模型結合超音波、微氣泡及奈米藥物Doxil探討其對於腫瘤治療的影響。大腸癌CT-26植入小鼠的左右兩耳，待腫瘤生長至15-20 mm3或50 mm3後開始治療，首先以靜脈注射方式給予抗癌藥物Doxil，再給予微氣泡(100 μl/kg)，而後立即於腫瘤處施打超音波(1 MHz、2 W/cm2、50% duty cycle、超音波施打總時間60秒)。腫瘤初始治療體積設定為15-20 mm3 (劑量為10 mg/kg Doxil)及50 mm3 (劑量為6 mg/kg Doxil及4 mg/kg Doxil)。實驗設計組包括:控制組、單純施打超音波、施打超音波及微氣泡、抗癌藥物有/無搭配超音波及微氣泡。 研究結果顯示:(1)小腫瘤(15-20 mm3)在接受抗癌藥物搭配超音波及微氣泡之治療後體積先升後降(雙相生長曲線)，但體積較大之腫瘤(50 mm3)在接受其治療後體積持續下降(單相生長曲線)；(2)對於腫瘤生長抑制，Doxil搭配超音波及微氣泡對腫瘤生長的抑制效果比只給予奈米藥物要來的顯著。(3)Doxil劑量為最終治療結果之重要影響因子。故搭配超音波及微氣泡可能有增強Doxil累積於腫瘤區域之效果，進而抑制腫瘤的生長。

In this study, mouse ear tumor model was employed to investigate the effects of ultrasound (US) sonication with microbubbles (MB) on tumor treatments with liposomal doxorubicin (Doxil). CT26 tumor cells were injected in both ears of the mice. When the tumors grew up to 15-20 mm3 (injected with 10mg/kg Doxil) or 50 mm3 (injected with 6 mg/kg Doxil or 4 mg/kg Doxil), the treatment was executed. Doxil was injected first, then MB (100 μl/kg) injection followed, and finally ultrasound (frequency: 1 MHz; intensity: 2 W/cm2; duty cycle: 50%; duration: 60 s) sonicated on the tumor immediately. Experiments included: control, US only, MB/US, Doxil without and with MB/US groups. The results showed that: 1) the tumor size increased and then decreased (biphasic growth pattern) for small tumors while decreased only (single-phase) for large tumors in Doxil with MB/US group; 2) for tumor growth suppression, Doxil with MB/US is more significant than Doxil alone during the treatment period; and 3) Doxil dose was the critical factor for the final treatment results. The results indicated that the application of MB/US might enhance the delivery of Doxil into tumor tissue and hence the tumor growth was hindered.