肝細胞癌是全球癌症第四大死因也是國人癌症第二大死因。針對無法以手術切除的肝細胞癌患者，經動脈灌流化學栓塞治療(Transarterial Chemoembolization, TACE)為現今最常使用的治療方法之一。然而，此治療方式卻有可能促進腫瘤血管新生及引起體內慢性發炎進而導致組織損傷。
在本研究中，嘗試開發新型球形、可生物降解、具治療協同作用的藥物載體粒子，以改善肝腫瘤栓塞與肝動脈灌注化療的治療效果。這些以多醣類為架構的新穎微米粒子(微粒)包含阿黴素(DOX)-硫酸軟骨素 (ChS)/殼聚醣(CS)、DOX-超順磁氧化鐵(SPIO)-ChS/CS與DOX-SPIO/棕櫚醯殼聚醣(NPCS)微粒等3項。微粒的顆粒型態及粒徑為利用穿透式以及掃描式電子顯微鏡進行分析，其粒徑大小為185±87nm至1.43 ±0.54μm之間。經由穿透式電子顯微鏡、X射線光電子能譜儀分析及核磁共振影像結果證實，SPIO成功包埋於微粒之中。在體外藥物釋放試驗結果，微粒顯示具有藥物緩釋作用，而DOX-SPIO/NPCS微粒在酸性環境(pH 6.5)比在鹼性環境下更能加速藥物之釋放。施予一外部磁場，微粒會呈現出加熱效應。在體外細胞毒性分析(MTT測試)，微粒比單純DOX溶液具有較佳的抗腫瘤能力。在體內試驗，將微粒投予以HepG2或Huh6細胞異體移植的裸鼠中，微粒比單純DOX溶液呈現更強的抗腫瘤作用。綜上，本研究結果顯示所製備之微粒具有相當的潛力作為肝癌治療的藥物傳輸系統。

Hepatocellular carcinoma(HCC) is the fourth leading cause of cancer-related death in the world and the second leading cause in Taiwan. For unresectable HCC, transcatheter arterial chemoembolization(TACE) is one of the current standard therapy, but it may promote a proangiogenic response at the tumor site and induce inflammation in the body.
In this study, new types of spherical, biodegradable, therapeutically synergistic, and drug-loadable delivery vehicles were developed to improve the efficacy of hepatic tumor embolization and hepatic artery infusion chemotherapy. A series of novel polysaccharide based microparticles(MPs) including doxorubicin(DOX)-chondroitin sulfate(ChS)/chitosan(CS), DOX-superparamagnetic iron oxide(SPIO)-ChS/CS and DOX-SPIO/N-palmitoyl chitosan(NPCS) MPs were prepared for hepatic cancer treatment. The morphology and size of the MPs were investigated by transmission and scanning electron microscopy. The MPs had the diameters from 185±87nm to 1.43±0.54 μm. The success of encapsulating SPIO was verified by transmission electron microscopy(TEM), X-ray photoelectron spectroscopy(XPS) and nuclear magnetic resonance T2 imaging(NMRI). In the drug release profile, the MPs showed slow releasing effect, and DOX-SPIO/NPCS MPs was accelerated in acidic environment(pH 6.5) compared with that in a basic environment. MPs present heating effects under external magnetic field. Results of cytotoxicity assay(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay) exhibited that MPs had better antitumor ability than free-form of DOX. According to the results of an animal study, the DOX-SPIO-ChS/CS MPs demonstrated stronger anti-tumor effect than free-form of DOX when it was administered to xenograft nude mice of HepG2/Huh6-bearing mice model in vivo. Thus, all these results suggested a considerable potential of MPs as a drug delivery system for hepatic cancer therapy.

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