肺腫瘤手術定位膠開發

Abstract

肺癌是世界上最常見且死亡率高的癌症之一，為降低肺癌死亡率，早期診斷非常重要。肺癌在初期階段大多呈現小型的惡性結節，可透過低劑量的CT (LDCT)來檢測出，但在開刀切除腫瘤時，因這些惡性結節體積小，難以透過肉眼或觸摸來確認位置，所以胸腔外科醫師在開刀切除前，會先請放射科醫師對病患肺部的惡性結節做定位，方法有植入帶鉤細金屬絲（hookwire），或是施打染劑（patent blue）到病灶來協助定位。然而現今的定位手術方法，除了會引起病人氣胸之外，裸露在病人胸腔外的金屬絲也會引起病患的恐懼和不便，而水溶性的染劑也會在病患呼吸或是移動時擴散，造成定位不精確或失敗。因此我們研發出一種帶有黏性和顏色的水膠，注射進病患肺部後，能夠緊緊的黏在病灶處不擴散，並且堵住定位手術時因針頭插入肺所造成的破洞，降低氣胸發生的機率，用以取代染劑和帶鉤金屬絲作為新型腫瘤定位材料。 近年研究發現，貽貝類的觸手在含水的環境下，依然能黏附在各種材料表面上，其因源自於牠的觸手能夠分泌出含大量鄰苯二酚（catechol）的黏液，鄰苯二酚的結構能與無機、有機物表面形成共價鍵和非共價鍵，進而產生黏性。因此，我們將同樣擁有此官能基的多巴胺（Dopamine）透過EDC/NHS反應接枝到具有高度生物相容性的褐藻酸鈉（sodium alginate）上，形成鄰苯二酚-褐藻酸鈉（catechol-alginate）。將此高分子和高碘酸鈉（NaIO4）混合，形成一種可注射式水膠。透過成膠時間、機械性質、組織拉伸、爆破壓力、以及細胞毒性的測試之後，確認我們研發的水膠具有適當黏性並且不具有細胞毒性，以利於應用在組織定位、修補肺部等臨床手術上。

Lung cancer is the most commonly occurring cancer in the world. To lower the mortality rate of lung cancer. Most of the early-stage lung tumors only present as small pulmonary nodules, which can be diagnosed by low-dose CT (LDCT).These nodules are too small to be observed through the naked eye or palpation during the resection surgery, so the radiologist usually locates the patient's nodules by implanting hookwire, or applying patent blue dye to the lesion before the surgical resection. However, the current localizing method not only cause pneumothorax but also bring fear and uncomfortable to patient due to the exposing hookwire outside patient's chest. The water-soluble dyes also spread when the patient breathes or moves, resulting in inaccurate or failure of pulmonary nodules localization. Thus, we have developed a colored adhesive hydrogel, which can be firmly adhered to the lesion after injection into the patient's lungs. Furthermore, it can block the injection hole to reduce the chance of pneumothorax, replacing the dye and hooked wire as a new material apply on pulmonary nodules localization. Recently, researches have showed that mussel can adhere to the surface of different materials in aqueous environment, due to the secretion of mucus containing a large amount of catechol group. Catechol can form covalent bonds and non-covalent bonds with the surface of inorganic and organic substances to generate adhesive ability. Therefore, we conjugated dopamine onto sodium alginate via EDC/NHS reaction to form catechol-sodium alginate. This polymer is mixed with sodium periodate (NaIO4) to form an injectable hydrogel. After testing the gelation time, mechanical properties, lap shear stress, burst pressure, and cytotoxicity, we confirmed that this hydrogel is biocompatible with appropriate adhesion ability for pulmonary nodules localization, and also be able to prevent pneumothorax.