(476e) Biofunctionalized Stimuli-Responsive Hydrogel Nanoparticles for RNAi Based Therapy in Inflammatory Bowel Diseases
In this work, we discuss the synthesis and optimization of functionalized hydrogel nanoparticle (nanogel) carriers for the targeted, intracellular delivery of siRNA. These nanogels are synthesized via an ARGET ATRP emulsion polymerization scheme and exhibit pH-dependent properties such that they protect the siRNA payload extracellularly and release its cargo upon cellular internalization. Furthermore, reactive monomers have been incorporated into the nanogels architecture for the subsequent conjugation of targeting ligands. The need for cell-specific targeting approaches for effective RNAi treatment is highlighted by the occurrence of off-target effects and non-specific toxicities due to the localization of these siRNA molecules in undesirable areas. To diminish these off-targets, it is imperative that siRNA molecules preferentially localize within the cell types of interest. In the case of IBDs, the cells of the innate immune system i.e. macrophages have been reported to play a pivotal role in the aberrant cytokine signaling observed during chronic inflammation in the gut. Therefore, a targeted approach which promotes the uptake of the functionalized siRNA loaded nanogels into macrophages could serve as a promising approach for more effective RNAi based therapies in IBDs.