Codelivery of doxorubicin and curcumin with lipid nanoparticles results in improved efficacy of chemotherapy in liver cancer.
Codelivery of doxorubicin and curcumin with lipid nanoparticles results in improved efficacy of chemotherapy in liver cancer.
复制标题
阿霉素和姜黄素与脂质纳米颗粒的共同递送可提高肝癌化疗的疗效
DOI：
10.2147/ijn.s73322
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发表时间：
2015
影响因子：
8
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Zhao X;Chen Q;Liu W;Li Y;Tang H;Liu X;Yang X
肝癌是全球癌症死亡的主要原因。纳米粒子负载的细胞毒性和化学增敏剂的联合治疗已被认为是治疗不同癌症的有效方法。然而，对肝癌的此类研究仍然非常有限。在我们的研究中，我们的目标是开发一种同时负载阿霉素(DOX)(一种有效的肝癌药物)和姜黄素(Cur)(一种化疗增敏剂)的新型脂质纳米粒，并观察其对肝癌的化疗效果。采用高压微流控技术成功制备了DOX和CuR共传递脂质纳米粒(DOX/CuR-NPs)，其平均粒径约为90 nm，多分散性指数为0.3，zeta电位为−为10 mV。DOX和Cur的包封率均为90%。空白脂质纳米粒是无毒的，通过对人正常肝细胞L02和肝癌细胞HepG2的细胞毒性研究确定。体外释放研究显示，DOX/CUR-NPs的缓释模式持续到48小时。我们发现DOX/cur-NPs对HepG2细胞的细胞毒作用增强，抑制浓度(IC)50降低，对L02细胞的细胞毒作用降低，提示与游离的DOX和DOX纳米粒(NPs)相比，DOX/cur-NPs具有协同作用。DOX和Cur的最佳重量比为1：1。Annexin-V-异硫氰酸荧光素/碘化丙啶双重染色显示，与游离的DOX和DOX-NPs相比，DOX/Cur-NPs处理的HepG2细胞的凋亡率明显增加。体内实验表明，DOX/CuR-NPs与DOX-NPs相比具有协同抑制肝癌生长的作用。综上所述，DOX/CUR-NPs同时传递DOX和CUR可能是治疗肝癌的一种有前途的治疗方法。
Liver cancer is a leading cause of cancer deaths worldwide. The combination therapy of cytotoxic and chemosensitizing agents loaded in nanoparticles has been highlighted as an effective treatment for different cancers. However, such studies in liver cancer remain very limited. In our study, we aim to develop a novel lipid nanoparticles loaded with doxorubicin (DOX) (an effective drug for liver cancer) and curcumin (Cur) (a chemosensitizer) simultaneously, and we examined the efficacy of chemotherapy in liver cancer. DOX and Cur codelivery lipid nanoparticles (DOX/Cur-NPs) were successfully prepared using a high-pressure microfluidics technique, showing a mean particle size of around 90 nm, a polydispersity index <0.3, and a zeta potential <−10 mV. The encapsulation efficacy was >90% for both DOX and Cur. The blank lipid nanoparticles were nontoxic, as determined by a cell cytotoxicity study in human normal liver cells L02 and liver cancer cells HepG2. In vitro DOX release studies revealed a sustained-release pattern until 48 hours in DOX/Cur-NPs. We found enhanced cytotoxicity and decreased inhibitory concentration (IC)50 in HepG2 cells and reduced cytotoxicity in L02 cells treated with DOX/Cur-NPs, suggesting the synergistic effects of DOX/Cur-NPs compared with free DOX and DOX nanoparticles (NPs). The optimal weight ratio of DOX and Cur was 1:1. Annexin-V-fluorescein isothiocyanate/propidium iodide double staining showed enhanced apoptosis in HepG2 cells treated with DOX/Cur-NPs compared with free DOX and DOX-NPs. An in vivo experiment showed the synergistic effect of DOX/Cur-NPs compared with DOX-NPs on liver tumor growth inhibition. Taken together, the simultaneous delivery of DOX and Cur by DOX/Cur-NPs might be a promising treatment for liver cancer.