Department of Nano Biotechnology, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
Int J Cancer. 2018 Oct 15;143(8):2017-2028. doi: 10.1002/ijc.31577. Epub 2018 Jul 10.
Modulating cancer causing genes with nucleic acid based-molecules as cutting-edge approaches need efficient delivery systems to succeed in clinic. Herein, we report design and fabrication of a novel tissue penetrating peptideticle with charge-structure switching in tumor microenvironment for an effective gene delivery. The comparative in vitro studies indicate that peptideticles identify and bind to tumor endothelial cells and efficiently penetrate into multicellular tumor spheroid. In addition, negatively charged peptideticle at pH 7.4, prevent unwanted interaction while its sharp charge-structure switching at pH 6.2-6.9 (e.g. in tumor tissue) facilitates malignant cells penetration. More importantly, upon systemic administration into tumor bearing mice, peptideticles effectively localized in tumor tissue and delivered luciferase gene with a 200-fold higher efficiency compared to their non-pH-responsive counterparts. In conclusion, this study presents a robust nanoassembly of safe materials for high efficient tumor gene delivery.
利用基于核酸的分子调节致癌基因是一种前沿方法，需要高效的传递系统才能在临床上取得成功。在此，我们报告了一种新型的组织穿透肽的设计和制备，该肽在肿瘤微环境中具有电荷-结构转换，可有效进行基因传递。体外比较研究表明，肽识别并结合肿瘤内皮细胞，并有效地穿透多细胞肿瘤球体。此外，在 pH 7.4 时带负电荷的肽可以防止不必要的相互作用，而在 pH 6.2-6.9 时（例如在肿瘤组织中）急剧的电荷-结构转换则有利于恶性细胞的穿透。更重要的是，在荷瘤小鼠中进行系统给药后，与非 pH 响应性对照物相比，肽在肿瘤组织中有效定位，并以 200 倍的效率递送荧光素酶基因。总之，本研究提出了一种基于安全材料的高效肿瘤基因传递的稳健纳米组装体。
