Conjugation of Doxorubicin to siRNA Through Disulfide-based Self-immolative Linkers.

ABSTRACT: Co-delivery systems of siRNA and chemotherapeutic drugs have been developed as an attractive strategy to optimize the efficacy of chemotherapy towards cancer cells with multidrug resistance. In these typical systems, siRNAs are usually associated to drugs within a carrier but without covalent interactions with the risk of a premature release and degradation of the drugs inside the cells. To address this issue, we propose a covalent approach to co-deliver a siRNA-drug conjugate with a redox-responsive self-immolative linker prone to intracellular glutathione-mediated disulfide cleavage. Herein, we report the use of two disulfide bonds connected by a pentane spacer or a p-xylene spacer as self-immolative linker between the primary amine of the anticancer drug doxorubicin (Dox) and the 2'-pos

SUBMITTER: Gauthier F 

PROVIDER: S-EPMC7321315 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature