Chang Cong, Liang Peiqing, Chen Linlin, Liu Junfeng, Chen Shihong, Zheng Guohua, Quan Changyun
a Key Laboratory of Chinese Medicine Resource and Compound Prescription of Ministry of Education , Hubei University of Chinese Medicine , Wuhan , P. R. China.
b Department of Biomedical Engineering , School of Engineering, Sun Yat-sen University , Guangzhou , P. R. China.
J Biomater Sci Polym Ed. 2017 Sep;28(13):1338-1350. doi: 10.1080/09205063.2017.1325095. Epub 2017 May 9.
In this paper, the peptide amphiphiles (PA) which consists of RGDSEEEEEEEEEEK as pH-sensitive segment and stearic acid as hydrophobic segment named RGDS-E-Lys(C) was successfully synthesized. TEM images showed that uniformly dispersed nanoparticles could be formed by PA molecules in pH 7.4 medium, however, disintegrated in pH 5.0 medium. Circular dichroism (CD) spectrum indicated that polypeptide adopted a random-coil conformation in neutral medium (pH 7.4). The CD signal was significantly attenuate for decreased solubility of PA in medium with pH 5.0. As expected, the prepared RGDS-E-Lys(C) assembly showed high pH-sensitive property which demonstrated a much more rapid drug release from micelles in tumor tissue (acidic environment) than in physiological environment (neutral environment). After DOX-loaded micelles incubated with tumor cells, the cytotoxicity of the micelles against Hela cells was increased obviously, indicating the great potential of micelles developed here as promising vehicle for targeted pH-responsive drug delivery.
在本文中，成功合成了一种肽两亲分子（PA），其由作为pH敏感片段的RGDSEEEEEEEEEEK和作为疏水片段的硬脂酸组成，命名为RGDS-E-Lys(C)。透射电子显微镜（TEM）图像显示，PA分子在pH 7.4的介质中可形成均匀分散的纳米颗粒，而在pH 5.0的介质中会解体。圆二色性（CD）光谱表明，该多肽在中性介质（pH 7.4）中呈无规卷曲构象。在pH 5.0的介质中，由于PA的溶解度降低，CD信号明显减弱。正如预期的那样，所制备的RGDS-E-Lys(C)组装体表现出高pH敏感性，这表明与生理环境（中性环境）相比，在肿瘤组织（酸性环境）中，药物从胶束中的释放速度要快得多。用负载阿霉素的胶束孵育肿瘤细胞后，胶束对Hela细胞的细胞毒性明显增加，表明这里开发的胶束作为有前景的靶向pH响应药物递送载体具有巨大潜力。
