Stepwise pH-responsive nanoparticles containing charge-reversible pullulan-based shells and poly(β-amino ester)/poly(lactic-co-glycolic acid) cores as carriers of anticancer drugs for combination therapy on hepatocellular carcinoma
Stepwise pH-responsive nanoparticles containing charge-reversible pullulan-based shells and poly(β-amino ester)/poly(lactic-co-glycolic acid) cores as carriers of anticancer drugs for combination therapy on hepatocellular carcinoma
复制标题
含有电荷可逆支链淀粉壳和聚(β-氨基酯)/聚(乳酸-乙醇酸)核的逐步pH响应纳米颗粒作为抗癌药物载体用于肝细胞癌联合治疗
DOI：
10.1016/j.jconrel.2016.02.030
复制
发表时间：
2016-03-28
影响因子：
10.8
通讯作者：
Wang, Yinsong
中科院分区：
文献类型：
--
作者：
Zhang, Cong;An, Tong;Wang, Yinsong
以电荷可逆普鲁兰多糖（CAPL）为壳，聚β-氨基酯（PBAE）/聚乳酸-羟基乙酸共聚物（PLAG）为核，构建了一种pH响应型纳米粒系统，用于紫杉醇（PTX）和考布他汀A4（CA 4）的联合抗血管生成和化疗治疗肝细胞癌（HCC）。CAPL/PBAE/PLGA（CAPL/PBAE/PLGA）纳米粒分别对弱酸性肿瘤微环境（pH约6.5）和内/溶酶体（pH约5.5）产生逐级反应，通过CAPL中β-羧酰胺键的断裂和PBAE的“质子-海绵”效应实现CA 4和PTX的高效有序释放。在人肝癌HepG 2细胞和人脐静脉内皮细胞中，CAPL/PBAE/PLGA纳米颗粒显着增强了PTX和CA 4对细胞增殖和细胞迁移的协同作用。在HepG 2荷瘤小鼠体内，CAPL/PBAE/PLGA纳米粒显示出良好的肿瘤靶向性，并显著增强PTX和CA 4对肿瘤生长和血管生成的抑制作用。总之，这种新的纳米颗粒系统是一个有前途的候选人作为载体的药物治疗肝癌。(C)2016爱思唯尔B. V.保留所有权利。
Stepwise pH-responsive nanoparticle system containing charge reversible pullulan-based (CAPL) shell and poly(beta-amino ester) (PBAE)/poly(lactic-co-glycolic acid) (PLAG) core is designed to be used as carriers of paclitaxel (PTX) and combretastatin A4 (CA4) for combining antiangiogenesis and chemotherapy to treat hepatocellular carcinoma (HCC). CAPL-coated PBAE/PLGA (CAPL/PBAE/PLGA) nanoparticles displayed step-by-step responses to weakly acidic tumor microenvironment (pH approximate to 6.5) and endo/lysosome (pH approximate to 5.5) respectively through the cleavage of beta-carboxylic amide bond in CAPL and the "proton-sponge" effect of PBAE, thus realized the efficient and orderly releases of CA4 and PTX. In human HCC HepG2 cells and human umbilical vein endothelial cells, CAPL/PBAE/PLGA nanoparticles significantly enhanced synergistic effects of PTX and CA4 on cell proliferation and cell migration. In HepG2 tumor-bearing mice, CAPL/PBAE/PLGA nanoparticles showed excellent tumor-targeting capability and remarkably increased inhibitory effects of PTX and CA4 on tumor growth and angiogenesis. In conclusion, this novel nanoparticle systemis a promising candidate as carrier for drugs against HCC. (C) 2016 Elsevier B.V. All rights reserved.