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

作者：Wang, Zhongyan; Zhao, Xiuli; Liu, Yan; Wang, Ting; Li, Kexin^*

来源：RSC Advances, 2018, 8(44): 25001-25007.

DOI：10.1039/c8ra02599a

• CATIONIC LIPOSOMES
• TARGETING TELOMERASE
• ENHANCED PERMEABILITY
• REVERSE-TRANSCRIPTASE
• CANCER THERAPEUTICS
• HTERT PROMOTES
• DRUG-DELIVERY
• INHIBITION
• INJECTION
• INVASION

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.

• 出版日期2018
• 单位沈阳药科大学