A Triazolium-Anchored Self-Immolative Linker Enables Self-Assembly-Driven siRNA Binding and Esterase-Induced Release.

ABSTRACT: The increased importance of RNA-based therapeutics comes with a need to develop next-generation stimuli-responsive systems capable of binding, transporting and releasing RNA oligomers. In this work, we describe triazolium-based amphiphiles capable of siRNA binding and enzyme-responsive release of the nucleic acid payload. In aqueous medium, the amphiphile self-assembles into nanocarriers that can disintegrate upon the addition of esterase. Key to the molecular design is a self-immolative linker that is anchored to the triazolium moiety and acts as a positively-charged polar head group. We demonstrate that addition of esterase leads to a degradation cascade of the linker, leaving the neutral triazole compound unable to form complexes and therefore releasing the negatively-charged siRNA. The

SUBMITTER: Hollstein S 

PROVIDER: S-EPMC10108132 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature