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Abstract：
OBJECTIVE: Cantharidin (CTD), the major component of the anti-cancer medicine obtained from Mylabris cichorii, exerts good inhibitory effects on several cancers, such as liver and breast cancer. However, owing to its toxicity, its oral administration can cause various adverse effects, limiting its clinical applications. Therefore, the development of a novel nano-drug delivery system for CTD would be highly beneficial.
METHODS: A nanostructured lipid carrier (NLC) was designed to actively target CTD to tumor cells using a hyaluronic acid (HA)-decorated copolymer (mPEG-NH2); the NLCs were called HA-mPEG-CTD-NLC. HA-mPEG was synthesized using amidation, and HA-mPEG-CTD-NLC was generated through ultrasonic emulsification in water. The mean hydrodynamic diameter of the particles was approximately 119.3 nm.
RESULTS: Pharmacokinetic studies revealed that the half-life of HA-mPEG-CTD-NLC and its area under the curve were higher than those of a CTD solution. Further, the plasma clearance rate of HA-mPEG-CTD-NLC was 0.41 times that of the CTD solution, implying a significantly prolonged drug retention time in vivo. Fluorescence in vivo endo-microscopy and optical in vivo imaging revealed that HA-mPEG-CTD-NLC had superior cytotoxicity and targeting efficacy against SMMC-7721 cells. An evaluation of the in vivo anti-tumor activity showed that HA-mPEG-CTD-NLC significantly inhibited tumor growth and prolonged survival in tumor-bearing mice, with a tumor inhibition rate of 65.96%.
CONCLUSIONS: Our results indicate that HA-mPEG-CTD-NLC may have great potential in liver cancer-targeted therapy.
METHODS: A nanostructured lipid carrier (NLC) was designed to actively target CTD to tumor cells using a hyaluronic acid (HA)-decorated copolymer (mPEG-NH2); the NLCs were called HA-mPEG-CTD-NLC. HA-mPEG was synthesized using amidation, and HA-mPEG-CTD-NLC was generated through ultrasonic emulsification in water. The mean hydrodynamic diameter of the particles was approximately 119.3 nm.
RESULTS: Pharmacokinetic studies revealed that the half-life of HA-mPEG-CTD-NLC and its area under the curve were higher than those of a CTD solution. Further, the plasma clearance rate of HA-mPEG-CTD-NLC was 0.41 times that of the CTD solution, implying a significantly prolonged drug retention time in vivo. Fluorescence in vivo endo-microscopy and optical in vivo imaging revealed that HA-mPEG-CTD-NLC had superior cytotoxicity and targeting efficacy against SMMC-7721 cells. An evaluation of the in vivo anti-tumor activity showed that HA-mPEG-CTD-NLC significantly inhibited tumor growth and prolonged survival in tumor-bearing mice, with a tumor inhibition rate of 65.96%.
CONCLUSIONS: Our results indicate that HA-mPEG-CTD-NLC may have great potential in liver cancer-targeted therapy.
摘要：
目标：斑蒿苷（CTD），抗癌药物的主要成分来自于Mylabriscichorii，对几种癌症有很好的抑制作用，如肝癌和乳腺癌。然而,由于其毒性,它的口服给药会引起各种副作用，限制其临床应用。因此,新型CTD纳米药物递送系统的开发将是非常有益的。
方法:纳米结构脂质载体(NLC)被设计为使用透明质酸(HA)修饰的共聚物(mPEG-NH2)将CTD主动靶向肿瘤细胞;NLC被称为HA-mPEG-CTD-NLC。HA-mPEG是使用酰胺化合成的，HA-mPEG-CTD-NLC通过在水中超声乳化产生。颗粒的平均流体动力学直径为约119.3nm。
结果：药代动力学研究表明，HA-mPEG-CTD-NLC的半衰期及其曲线下面积高于CTD溶液。Further,HA-mPEG-CTD-NLC的血浆清除率是CTD溶液的0.41倍，这意味着药物在体内的保留时间显著延长。荧光体内显微镜和光学体内成像显示HA-mPEG-CTD-NLC对SMMC-7721细胞具有优异的细胞毒性和靶向功效。对体内抗肿瘤活性的评估表明，HA-mPEG-CTD-NLC显着抑制荷瘤小鼠的肿瘤生长并延长生存期，抑瘤率为65.96%。
结论：我们的结果表明HA-mPEG-CTD-NLC可能在肝癌靶向治疗中具有巨大潜力。
方法:纳米结构脂质载体(NLC)被设计为使用透明质酸(HA)修饰的共聚物(mPEG-NH2)将CTD主动靶向肿瘤细胞;NLC被称为HA-mPEG-CTD-NLC。HA-mPEG是使用酰胺化合成的，HA-mPEG-CTD-NLC通过在水中超声乳化产生。颗粒的平均流体动力学直径为约119.3nm。
结果：药代动力学研究表明，HA-mPEG-CTD-NLC的半衰期及其曲线下面积高于CTD溶液。Further,HA-mPEG-CTD-NLC的血浆清除率是CTD溶液的0.41倍，这意味着药物在体内的保留时间显著延长。荧光体内显微镜和光学体内成像显示HA-mPEG-CTD-NLC对SMMC-7721细胞具有优异的细胞毒性和靶向功效。对体内抗肿瘤活性的评估表明，HA-mPEG-CTD-NLC显着抑制荷瘤小鼠的肿瘤生长并延长生存期，抑瘤率为65.96%。
结论：我们的结果表明HA-mPEG-CTD-NLC可能在肝癌靶向治疗中具有巨大潜力。
