CAS Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory of Marine Science and Technology, Qingdao 266237, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao 266071, China.
CAS Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Laboratory for Marine Drugs and Bioproducts, Qingdao National Laboratory of Marine Science and Technology, Qingdao 266237, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao 266071, China.
Int J Biol Macromol. 2019 Apr 1;126:662-672. doi: 10.1016/j.ijbiomac.2018.12.262. Epub 2018 Dec 29.
A gastric cancer angiogenesis marker peptide, GX1, is promising to be a desirable ligand for anti-angiogenesis targeted drug of gastric cancer treatment. In this study, GX1 was utilized to fabricate a multifunctional vascular targeting docetaxel (DCT)-loaded nanoparticle with N-deoxycholic acid glycol chitosan (DGC) as the carrier and GX1-PEG-deoxycholic acid (GPD) conjugate as the targeting ligand. The mean size of obtained GX1-DGC-DCT was 150.9 nm with a narrow size distribution and their shape was spherical with smooth surface texture. The in vitro drug release test revealed a sustained release manner and an acid pH could accelerate the release compared with the neutral pH. Furthermore, GX1-DGC-DCT showed stronger cytotoxicity against co-cultured gastric cancer cells and human umbilical vein endothelial cells (co-HUVEC) than DCT within 100 μM. In addition, GX1 efficiently enhanced the cellular uptake of nanoparticles in co-HUVEC cells as confirmed by confocal fluorescence scanning microscopy. Moreover, in vivo delivery of GX1-DGC-DCT was demonstrated to inhibit tumor growth in SGC791 tumor-bearing mice with tumor inhibition rate (TIR) of 67.05% and no weight loss of mice was observed. The anti-tumor effects were further confirmed by H&E and TUNEL analysis. Therefore, this new drug delivery system represents a potential strategy for gastric cancer therapy.
一种胃癌血管生成标记肽 GX1 有望成为治疗胃癌的抗血管生成靶向药物的理想配体。在这项研究中，利用 GX1 制备了一种多功能血管靶向载多西紫杉醇（DCT）纳米粒子，以 N-去氧胆酸乙二醇壳聚糖（DGC）为载体，GX1-PEG-去氧胆酸（GPD）缀合物为靶向配体。所得 GX1-DGC-DCT 的平均粒径为 150.9nm，粒径分布较窄，形状为球形，表面光滑。体外药物释放试验表明，与中性 pH 相比，酸性 pH 可加速释放，呈持续释放方式。此外，在 100μM 以内，GX1-DGC-DCT 对共培养的胃癌细胞和人脐静脉内皮细胞（co-HUVEC）的细胞毒性强于 DCT。此外，共聚焦荧光扫描显微镜证实，GX1 可有效增强 co-HUVEC 细胞中纳米颗粒的细胞摄取。此外，体内实验结果表明，GX1-DGC-DCT 能抑制 SGC791 荷瘤小鼠肿瘤生长，肿瘤抑制率（TIR）为 67.05%，且未观察到小鼠体重减轻。H&E 和 TUNEL 分析进一步证实了该药物的抗肿瘤作用。因此，这种新的药物传递系统为胃癌治疗提供了一种有潜力的策略。
