Functional alginate nanoparticles for efficient intracellular release of doxorubicin and hepatoma carcinoma cell targeting therapy
Functional alginate nanoparticles for efficient intracellular release of doxorubicin and hepatoma carcinoma cell targeting therapy
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功能性海藻酸盐纳米粒子用于有效细胞内释放阿霉素和肝癌细胞靶向治疗
DOI：
10.1016/j.ijpharm.2013.04.025
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发表时间：
2013-07-15
影响因子：
5.8
通讯作者：
Yuan, Zhi
中科院分区：
文献类型：
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作者：
Guo, Hua;Lai, Quanyong;Yuan, Zhi
为了有效地将化疗药物递送到肝癌细胞中，制备了pH敏感的肝靶向药物递送系统（大黄酸修饰的海藻酸盐/阿霉素修饰的海藻酸盐复合纳米粒），称为GA-ALG/DOX-ALG NPs。首先合成了GA-ALG和DOX-ALG，然后通过透析将GA-ALG和DOX-ALG混合自组装成GA-ALG/DOX-ALG纳米粒。评价了纳米粒的pH敏感性、小鼠体内分布和对异位肝癌肿瘤的抗肿瘤活性。GA-ALG/DOX-ALG NP的DOX释放显示pH敏感性;在pH 7.4下9 d内释放不到10%的药物，而在pH 4.0下释放58.7%的DOX。共聚焦激光扫描显微镜（CLSM）实验表明，GA-ALG/DOX-ALG NPs能够响应内体/溶酶体环境，并具有pH触发的细胞内释放特性。GA-ALG/DOX-ALG NP在肝脏中的曲线下面积（AUC（0-无穷大））和半衰期（t（1/2））分别为1156.7 μ g h/g和34.3 h，分别比DOX中心点HCl组高11.8倍和3.2倍。GA-ALG/DOX-ALG NPs对肿瘤生长的抑制率为79.3%，明显高于DOX中心点盐酸盐组（48.5%）和DOX-ALG NPs组（62.7%）。重要的是，GA-ALG/DOX-ALG NP组中没有小鼠死亡，而DOX中心点HCl组中的死亡率为40%。(c)2013 Elsevier B. V.保留所有权利。
In order to efficiently deliver chemotherapy drugs into hepatoma cells, a pH-sensitive and liver-targeted drug delivery system (glycyrrhetinic acid-modified alginate/doxorubicin-modified alginate complex nanoparticles), termed GA-ALG/DOX-ALG NPs, was prepared. First, GA-ALG and DOX-ALG were synthesized, and then GA-ALG/DOX-ALG NPs self-assembled by mixing GA-ALG and DOX-ALG via dialysis. Properties of pH-sensitivity, biodistribution in mice, and antitumor activity against ectopic hepatoma tumors in the NPs were evaluated. DOX release from GA-ALG/DOX-ALG NPs showed pH-sensitivity; less than 10% of drugs were liberated at pH 7.4 within 9 d while 58.7% of DOX released at pH 4.0. The confocal laser scanning microscope (CLSM) experiment showed that GA-ALG/DOX-ALG NPs can respond to the endosomal/lysosomal environment and had pH-triggered intracellular releasing property. The area under the curve (AUC(0-infinity)) and half-life (t(1/2)) in the liver of GA-ALG/DOX-ALG NPs were 1156.7 mu g h/g and 34.3 h, respectively, which was 11.8- and 3.2-fold higher than that of the DOX center dot HCl group. Furthermore, the inhibition rate of tumor growth was 79.3% after treatment with GA-ALG/DOX-ALG NPs, which was much higher than that of the DOX center dot HCl (48.5%) and DOX-ALG NPs groups (62.7%). Importantly, no mice died in the GA-ALG/DOX-ALG NPs group, while the mortality rate was 40% in the DOX center dot HCl group. (c) 2013 Elsevier B.V. All rights reserved.