a Tianjin State Key Laboratory of Modern Chinese Medicine, Institute of Traditional Chinese Medicine , Tianjin University of Traditional Chinese Medicine , Tianjin , P.R. China.
b Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education , Tianjin University of Traditional Chinese Medicine , Tianjin , P.R. China.
Drug Deliv. 2018 Nov;25(1):757-765. doi: 10.1080/10717544.2018.1446474.
Tumor-targeted delivery is considered a crucial component of current anticancer drug development and is the best approach to increase the efficacy and reduce the toxicity. Nanomedicine, particularly ligand-based nanoparticles have shown a great potential for active targeting of tumor. Cell penetrating peptide is one of the promising ligands in a targeted cancer therapy. In this study, the gambogic acid-loaded nanostructured lipid carrier (GA-NLC) was modified with two kinds of cell penetrating peptides (cRGD and RGERPPR). The GA-NLC was prepared by emulsification and solvent evaporation method and coupled with cRGD, RGERPPR, and combination cRGD and RGERPPR to form GA-NLC-cRGD, GA-NLC-RGE, and GA-NLC-cRGD/RGE, respectively. The formulations were characterized by their particle size and morphology, zeta potential, encapsulation efficiency, and differential scanning calorimetry. In vitro cytotoxicity and cellular uptake study of the formulations were performed against breast cancer cell (MDA-MB-231). Furthermore, in vivo biodistribution and antitumor activity of the formulations were determined by in vivo imaging and in tumor-bearing nude mice, respectively. The result of in vitro cytotoxicity study showed that GA-NLC-RGE exhibited a significantly higher cytotoxicity on MDA-MB-231 as compared with GA-NLC and GA-Sol. Similarly, RGE-Cou-6-NLC showed remarkably higher uptake by the cells than other NLCs over the incubation period. The in vivo imaging study has demonstrated that among the formulations, the RGE-decorated DiR-NLC were more accumulated in the tumor site. The in vivo antitumor activity revealed that RGE-GA-NLC inhibits the tumor growth more efficiently than other formulations. In conclusion, RGERPPR has a potential as an effective carrier in targeting drug delivery of anticancer agents.
肿瘤靶向递药被认为是当前抗癌药物开发的关键组成部分，是提高疗效、降低毒性的最佳途径。纳米医学，特别是配体纳米粒，在肿瘤主动靶向方面显示出巨大的潜力。细胞穿透肽是靶向癌症治疗中一种很有前途的配体。在本研究中，负载藤黄酸的纳米结构脂质载体（GA-NLC）用两种细胞穿透肽（cRGD 和 RGERPPR）进行了修饰。GA-NLC 采用乳化溶剂蒸发法制备，并与 cRGD、RGERPPR 以及 cRGD 和 RGERPPR 的组合偶联，分别形成 GA-NLC-cRGD、GA-NLC-RGE 和 GA-NLC-cRGD/RGE。通过粒径和形态、Zeta 电位、包封效率和差示扫描量热法对制剂进行了表征。对制剂进行了体外细胞毒性和细胞摄取研究，针对乳腺癌细胞（MDA-MB-231）。此外，通过体内成像和荷瘤裸鼠分别测定了制剂的体内分布和抗肿瘤活性。体外细胞毒性研究结果表明，与 GA-NLC 和 GA-Sol 相比，GA-NLC-RGE 对 MDA-MB-231 表现出更高的细胞毒性。同样，RGE-Cou-6-NLC 在孵育期间比其他 NLC 表现出更高的细胞摄取率。体内成像研究表明，在这些制剂中，RGE 修饰的 DiR-NLC 更多地聚集在肿瘤部位。体内抗肿瘤活性表明，RGERPPR 作为一种有效的载体，具有抑制肿瘤生长的潜力。总之，RGERPPR 作为一种有效的载体，具有靶向抗癌药物递药的潜力。
