Wang Zhongyan, Zhao Xiuli, Liu Yan, Wang Ting, Li Kexin
School of Pharmacy, Shenyang Pharmaceutical University Liaoning Province China
RSC Adv. 2018 Jul 11;8(44):25001-25007. doi: 10.1039/c8ra02599a. eCollection 2018 Jul 9.
An unusual enzyme called telomerase acts on parts of chromosomes known as telomeres. The enzyme has recently been found in many human tumors and is viewed as a new target for tumor therapy. In this research, we chose the analogue of guanine "2',3'-dideoxyguanosine" (ddG) as the telomerase inhibitor and prepared the ddG-loaded cationic nanoliposomes (ddG-Clip) to specifically target the tumor tissue and preferentially occupy the telomerase nucleotide binding site. The mean diameter of ddG-Clip is 101.54 ± 2.60 nm and they are cationically charged with a zeta potential of 34.0 ± 9.43 mV; also, the encapsulation efficiency of ddG-Clip is 53.44% ± 2.29%. cytotoxicity results show that cationic nanoliposomes by themselves are almost non-toxic, but with the increase in ddG concentration, ddG-Clip has the ability to kill S180 tumor cells. The anti-tumor activity study suggests that ddG-Clip could not only suppress the tumor growth, but also inhibit tumor liver metastasis well. In conclusion, reverse transcriptase inhibitor-loaded cationic nanoliposomes could interfere with the synthesis of telomeric DNA and block abnormal proliferation of tumor cells, therefore achieving tumor apoptosis.
一种名为端粒酶的特殊酶作用于染色体上被称为端粒的部分。最近在许多人类肿瘤中发现了这种酶，并被视为肿瘤治疗的新靶点。在本研究中，我们选择鸟嘌呤类似物“2',3'-二脱氧鸟苷”（ddG）作为端粒酶抑制剂，并制备了负载ddG的阳离子纳米脂质体（ddG-Clip），以特异性靶向肿瘤组织并优先占据端粒酶核苷酸结合位点。ddG-Clip的平均直径为101.54±2.60nm，带正电荷，zeta电位为34.0±9.43mV；此外，ddG-Clip的包封率为53.44%±2.29%。细胞毒性结果表明，阳离子纳米脂质体本身几乎无毒，但随着ddG浓度的增加，ddG-Clip具有杀死S180肿瘤细胞的能力。抗肿瘤活性研究表明，ddG-Clip不仅可以抑制肿瘤生长，还可以很好地抑制肿瘤肝转移。总之，负载逆转录酶抑制剂的阳离子纳米脂质体可以干扰端粒DNA的合成，阻断肿瘤细胞的异常增殖，从而实现肿瘤细胞凋亡。
