N-trimethyl chitosan nanoparticle-encapsulated lactosyl-norcantharidin for liver cancer therapy with high targeting efficacy
N-trimethyl chitosan nanoparticle-encapsulated lactosyl-norcantharidin for liver cancer therapy with high targeting efficacy
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DOI：
10.1016/j.nano.2012.01.009
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发表时间：
2012-10-01
影响因子：
5.4
通讯作者：
Zhang, Qiang
中科院分区：
文献类型：
--
作者：
Guan, Min;Zhou, Yi;Zhang, Qiang
合成了n -三甲基壳聚糖（TMC），并采用离子交联法制备了去斑蝥素乳基TMC纳米粒（Lac-NCTD-TMC-NPs）。得到的Lac-NCTD-TMC-NPs平均粒径为120.6 +/- 1.7 nm，包封效率为69.29% +/- 0.76%，载药量为9.1% +/- 0.07%。通过透析法研究Lac-NCTD-TMC-NPs的体外释放，其持续效果明显。在人肝癌细胞株HepG2中，tmc包封的Lac-NCTD （Lac-NCTD- tmc - nps）在24小时的半最大抑制浓度（IC50）仅为游离Lac-NCTD的24.2%。Lac-NCTD通过触发细胞凋亡诱导HepG2细胞死亡。体外细胞摄取和体内近红外荧光实时成像均显示出高靶向性。与Lac-NCTD和Lac-NCTD壳聚糖NPs （Lac-NCTD- cs -NPs）相比，Lac-NCTD- tmc -NPs对小鼠肝癌22皮下模型的抗肿瘤活性最强。本文描述了n-三甲基壳聚糖包封的去甲斑蝥素纳米颗粒的制备，在肝癌SC小鼠模型中显示出有效的靶向性和缓释性。(C) 2012爱思唯尔公司版权所有。
N-Trimethyl chitosan (TMC) was synthesized and used to prepare lactosyl-norcantharidin TMC nanoparticles (Lac-NCTD-TMC-NPs) using an ionic cross-linkage process. Lac-NCTD-TMC-NPs with an average particle size of 120.6 +/- 1.7 nm were obtained, with an entrapment efficiency of 69.29% +/- 0.76%, and a drug-loading amount of 9.1% +/- 0.07%. The release of Lac-NCTD-TMC-NPs in vitro was investigated through a dialysis method, and its sustained effect was evident. In the human liver cancer cell line HepG2, the half-maximum inhibiting concentration (IC50) of TMC-encapsulated Lac-NCTD (Lac-NCTD-TMC-NPs) was only 24.2% that of free Lac-NCTD at 24 hours. Lac-NCTD induced HepG2 cell death by triggering apoptosis. In vitro cellular uptake and in vivo NIR fluorescence real-time imaging both indicated a high targeting efficacy. In comparison with Lac-NCTD and Lac-NCTD chitosan NPs (Lac-NCTD-CS-NPs), Lac-NCTD-TMC-NPs had the strongest antitumor activity on the murine hepatocarcinoma 22 subcutaneous model.From the Clinical Editor: In this article the preparation of N-trimethyl chitosan-encapsulated lactosyl-norcantharidin nanoparticles is described that displayed efficient targeting and sustained release in a hepatocarcinoma SC murine model. (C) 2012 Elsevier Inc. All rights reserved.