TY - JOUR
T1 - Selective Anti-melanoma Effect of Phosphothioated Aptamer Encapsulated by Neutral Cytidinyl/Cationic Lipids
AU - Wu, Jing
AU - Wang, Shuhe
AU - Li, Xiang
AU - Zhang, Qi
AU - Yang, Jie
AU - Ma, Yuan
AU - Guan, Zhu
AU - Yang, Zhenjun
N1 - Funding information:
This work was supported by the Ministry of Science and Technology of China (Grant No. 2017ZX09303013) and the National Natural Science Foundation of China (Grant No. 21778006).
Publisher copyright:
© 2021 Wu, Wang, Li, Zhang, Yang, Ma, Guan and Yang.
PY - 2021/6/28
Y1 - 2021/6/28
N2 - BC15-31 is a DNA aptamer that targets heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), which plays a crucial role in the process of pre-RNA maturation and is also essential for the rapid proliferation of tumor cells. In this research, we modified BC15-31 with a phosphorothioate (PS) backbone, LNA, and 2-O-MOE to enhance its stability and target affinity. In addition, a neutral cytidinyl lipid (DNCA) and a cationic lipid (CLD) were mixed to encapsulate modified aptamers with the aim of improving their cell permeability with low toxicity. Under the DNCA/CLD package, aptamers are mainly distributed in the nucleus. A modified sequence WW-24 showed an excellent selective anti-melanoma (A375 cells, ∼25 nM, 80%) activity, targeted to both hnRNP A1 and hnRNP A2/B1 found by the BLI experiment, and induced more early and late apoptosis in vitro, which also showed stronger antitumor effect and longer accumulation time in vivo. These results provide a new strategy for further clinical applications.
AB - BC15-31 is a DNA aptamer that targets heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), which plays a crucial role in the process of pre-RNA maturation and is also essential for the rapid proliferation of tumor cells. In this research, we modified BC15-31 with a phosphorothioate (PS) backbone, LNA, and 2-O-MOE to enhance its stability and target affinity. In addition, a neutral cytidinyl lipid (DNCA) and a cationic lipid (CLD) were mixed to encapsulate modified aptamers with the aim of improving their cell permeability with low toxicity. Under the DNCA/CLD package, aptamers are mainly distributed in the nucleus. A modified sequence WW-24 showed an excellent selective anti-melanoma (A375 cells, ∼25 nM, 80%) activity, targeted to both hnRNP A1 and hnRNP A2/B1 found by the BLI experiment, and induced more early and late apoptosis in vitro, which also showed stronger antitumor effect and longer accumulation time in vivo. These results provide a new strategy for further clinical applications.
KW - aptamer
KW - phosphorothioate
KW - cytidinyl lipid
KW - hnRNP A2/B1
KW - Liposome
UR - https://www.scopus.com/inward/record.uri?eid=2-s2.0-85109837851&doi=10.3389%2ffcell.2021.660233&partnerID=40&md5=153f24d938a9bd8036f999d5d64453f5
U2 - 10.3389/fcell.2021.660233
DO - 10.3389/fcell.2021.660233
M3 - Journal article
SN - 2296-634X
VL - 9
JO - Frontiers in Cell and Developmental Biology
JF - Frontiers in Cell and Developmental Biology
M1 - 660233
ER -
