Abstract
For the first time, a novel dithiomaleimides (DTM) based tetra-antennary GalNAc conjugate was developed, which enable both efficient siRNA delivery and good traceability, without incorporating extra fluorophores. This conjugate can be readily constructed by three click-type reactions, that is, amidations, thiol-dibromomaleimide addition and copper catalyzed azide-alkyne cycloaddition (CuAAC). And it also has comparable siRNA delivery efficiency, with a GalNAc L96 standard to mTTR target. Additionally, due to the internal DTMs, a highly fluorescent emission was observed, which benefited delivery tracking and reduced the cost and side effects of the extra addition of hydrophobic dye molecules. In all, the simple incorporation of DTMs to the GalNAc conjugate structure has potential in gene therapy and tracking applications.
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