载姜黄素双靶向阿仑膦酸钠-透明质酸-十八烷酸胶束提高骨肉瘤治疗效果。

INTRODUCTION: Curcumin (CUR) is a general ingredient of traditional Chinese medicine, which has potential antitumor effects. However, its use clinically has been limited due to its low aqueous solubility and bioavailability. In order to improve the therapeutic effect of CUR on osteosarcoma (i.e., bone cancer), a multifunctional micelle was developed here by combining active bone accumulating ability with tumor CD44 targeting capacity. METHODS: The CUR loaded micelles were self-assembled by using alendronate-hyaluronic acid-octadecanoic acid (ALN-HA-C18) as an amphiphilic material. The obtained micelles were characterized for size and drug loading. In addition, the in vitro release behavior of CUR was investigated under PBS (pH 5.7) medium containing 1% Tween 80 at 37℃. Furthermore, an hydroxyapatite (the major inorganic component of bone) affinity experiment was studied. In vitro antitumor activity was evaluated. Finally, the anti-tumor efficiency was studied. RESULTS: The size and drug loading of the CUR loaded ALN-HA-C18 micelles were about 118 ± 3.6 nm and 6 ± 1.2%, respectively. CUR was released from the ALN-HA-C18 micelles in a sustained manner after 12 h. The hydroxyapatite affinity experiment indicated that CUR loaded ALN-HA-C18 micelles exhibited a high affinity to bone. CUR loaded ALN-HA-C18 micelles exhibited much higher cytotoxic activity against MG-63 cells compared to free CUR. Finally, CUR loaded ALN-HA-C18 micelles effectively delayed anti-tumor growth properties in osteosarcoma bearing mice as compared with free CUR. CONCLUSION: The present study suggested that ALN-HA-C18 is a novel promising micelle for osteosarcoma targeting and delivery of the hydrophobic anticancer drug CUR.

简介：姜黄素（CUR）是一种中药的常用成分，具有潜在的抗肿瘤作用。然而，由于其低水溶性和生物利用度，其在临床上的应用受到限制。为了提高 CUR 对骨肉瘤（即骨癌）的治疗效果，本研究通过结合主动骨积累能力和肿瘤 CD44 靶向能力，开发了一种多功能胶束。

方法：采用阿仑膦酸钠-透明质酸-十八烷酸（ALN-HA-C18）作为两亲性材料自组装载药胶束。对所得胶束的粒径及载药量进行了考察。此外，还考察了 CUR 在 PBS（pH5.7）介质中 1%吐温 80 存在下 37℃下的体外释放行为。进一步研究了羟基磷灰石（骨的主要无机成分）亲和实验。评价了体外抗肿瘤活性。最后，研究了抗瘤效率。

结果：载 CUR 的 ALN-HA-C18 胶束的粒径和载药量约为 118±3.6nm 和 6±1.2%。CUR 从 ALN-HA-C18 胶束中以持续的方式释放，12 小时后释放。羟基磷灰石亲和实验表明，载 CUR 的 ALN-HA-C18 胶束对骨具有高亲和力。与游离 CUR 相比，载 CUR 的 ALN-HA-C18 胶束对 MG-63 细胞表现出更高的细胞毒性。最后，与游离 CUR 相比，载 CUR 的 ALN-HA-C18 胶束在荷骨肉瘤小鼠体内有效延缓了抗肿瘤生长作用。

结论：本研究表明，ALN-HA-C18 是一种新型的有前途的胶束，可用于骨肉瘤靶向和疏水性抗癌药物 CUR 的递送。