Anti-GPC3 antibody-modified sorafenib-loaded nanoparticles significantly inhibited HepG2 hepatocellular carcinoma.
Anti-GPC3 antibody-modified sorafenib-loaded nanoparticles significantly inhibited HepG2 hepatocellular carcinoma.
复制标题
抗GPC3抗体修饰索拉非尼纳米粒显着抑制HepG2肝细胞癌
DOI：
10.1080/10717544.2018.1477859
复制
发表时间：
2018-11
期刊：
影响因子：
6
通讯作者：
Ma D
中科院分区：
文献类型：
--
作者：
Tang X;Chen L;Li A;Cai S;Zhang Y;Liu X;Jiang Z;Liu X;Liang Y;Ma D
摘要索拉非尼（SFB）改善了肝细胞癌（HCC）的治疗效果，且与其他药物相比具有更少的严重副作用。然而，由于缺乏肿瘤特异性靶向，药物在肿瘤组织中的浓度不能永久维持在抑制肿瘤生长的水平。为了克服这个问题，我们开发了一种新型的SFB负载的聚合物纳米颗粒（NP）。NP（由ε-己内酯和d-α-生育酚聚乙二醇1000琥珀酸酯（TPGS）通过开环聚合合成的TPGS-b-PCL共聚物）含有Pluronic P123和SFB，并且其表面用抗GPC 3抗体修饰以产生聚合物纳米颗粒（NP-SFB-Ab）。Ab缀合的纳米颗粒具有比非抗体缀合的含SPD的纳米颗粒（NP-SFB）更高的HepG 2细胞摄取。NP-SFB-Ab还显示出更好的稳定性特征，释放更高水平的SFB到细胞培养基中，并且比非靶向NP-SFB和游离SFB对肿瘤细胞更具细胞毒性。NP-SFB-Ab下调了抗凋亡分子MCL-1的表达，导致线粒体胞浆中Bax和巴克的聚合。NP-SFB-AB还促进线粒体释放细胞色素C，导致细胞凋亡。NP-SFB-Ab对HepG 2裸鼠移植瘤的生长有明显的抑制作用，且无明显毒副作用。这些结果表明，NP-SFB-Ab是一种很有前途的肝癌靶向治疗新方法。
Abstract Sorafenib (SFB) has improved the treatment of hepatocellular carcinoma (HCC) and has fewer severe side effects than other agents used for that purpose. However, due to a lack of tumor-specific targeting, the concentration of the drug in tumor tissue cannot be permanently maintained at a level that inhibits tumor growth. To overcome this problem, we developed a novel SFB-loaded polymer nanoparticle (NP). The NP (a TPGS-b-PCL copolymer that was synthesized from ε-caprolactone and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) via ring-opening polymerization) contains Pluronic P123 and SFB, and its surface is modified with anti-GPC3 antibody to produce the polymer nanoparticle (NP-SFB-Ab). The Ab-conjugated NPs had higher cellular uptake by HepG2 cells than did non-antibody-conjugated SPD-containing nanoparticles (NP-SFB). The NP-SFB-Ab also displayed better stability characteristics, released higher levels of SFB into cell culture medium, and was more cytotoxic to tumor cells than was non-targeted NP-SFB and free SFB. The NP-SFB-Ab downregulated expression of the anti-apoptosis molecule MCL-1, which led to polymerization of Bax and Bak in mitochondrial cytosol. The NP-SFB-AB also promoted the mitochondrial release of cytochrome C, resulting in cellular apoptosis. Moreover, the NP-SFB-Ab significantly inhibited the growth of HepG2 xenograft tumors in nude mice without producing obvious side effects. These findings suggest that NP-SFB-Ab is a promising new method for achieving targeted therapy of HCC.
登录
查看更多内容
影响因子：
16.6
作者：
Inoue-Yamauchi A;Jeng PS;Kim K;Chen HC;Han S;Ganesan YT;Ishizawa K;Jebiwott S;Dong Y;Pietanza MC;Hellmann MD;Kris MG;Hsieh JJ;Cheng EH
通讯作者：
Cheng EH
影响因子：
8
作者：
Tang X;Zhu H;Sun L;Hou W;Cai S;Zhang R;Liu F
通讯作者：
Liu F
影响因子：
--
作者：
Mei L;Zhang Y;Zheng Y;Tian G;Song C;Yang D;Chen H;Sun H;Tian Y;Liu K;Li Z;Huang L
通讯作者：
Huang L
影响因子：
6
作者：
Parikh A;Kathawala K;Tan CC;Garg S;Zhou XF
通讯作者：
Zhou XF
影响因子：
7.5
作者：
Ansari, Shabbir A.;Pendurthi, Usha R.;Rao, L. Vijaya Mohan
通讯作者：
Rao, L. Vijaya Mohan