Dumbbell-Shaped Antisense Oligonucleotide Prodrugs Showed Improved Antinuclease Stability and Anticancer Efficacy

Autor:	Zhe Zhang, Hongqian Ren, Zuyi Chen, Yaling Zhang, Zhuolin Zhang, Yuan Luo, Shiyuan Wang, Xuesong Feng, Liang Xu
Rok vydání:	2022
Předmět:	Mice Neoplasms Drug Discovery Tumor Microenvironment Animals Humans Mice Nude Pharmaceutical Science Molecular Medicine Prodrugs Disulfides Oligonucleotides Antisense
Zdroj:	Molecular Pharmaceutics. 19:3915-3921
ISSN:	1543-8392 1543-8384
DOI:	10.1021/acs.molpharmaceut.2c00396
Popis:	Antisense oligonucleotides (ASONs) have generated widespread interest as antitumor agents. Nevertheless, the utility of natural ASONs is limited due to their rapid degradation by intracellular and extracellular nucleases. In this work, we proposed a novel prodrug-type ASON with a dumbbell conformation and a responsive disulfide switch. A degradation assay showed that the dumbbell-shaped ASON (DS-ASON) exhibited stronger stability against enzymatic degradation compared with that of the linear or single-end looped ASON. The native ASON could dissociate
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::009d25376f8febe1524daac09b32673c https://doi.org/10.1021/acs.molpharmaceut.2c00396 Zobrazit plný text záznamu