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New therapeutic strategies based on interference with telomeric DNA synthesis of tumor cells to suppress the growth of tumors

机译：基于干扰肿瘤细胞端粒DNA合成以抑制肿瘤生长的新治疗策略

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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%. In vitro 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.
机译：一种称为端粒酶的异常酶作用于称为端粒的染色体部分。该酶最近在许多人类肿瘤中被发现，并被视为肿瘤治疗的新靶标。在这项研究中，我们选择鸟嘌呤“ 2'，3'-dideoxyguanosine”（ddG）的类似物作为端粒酶抑制剂，并制备了载有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±2.60 nm，并且它们以34.0±9.43 mV的zeta阳离子带电。此外，ddG-Clip的封装效率为53.44％±2.29％。体外细胞毒性结果表明，阳离子纳米脂质体本身几乎没有毒性，但是随着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不仅可以抑制肿瘤的生长，而且可以很好地抑制肿瘤的肝转移。总之，负载逆转录酶抑制剂的阳离子纳米脂质体可能干扰端粒DNA的合成并阻断肿瘤细胞的异常增殖，从而实现肿瘤细胞凋亡。

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