Overproduction of tumor necrosis factor-a (TNF-a) by macrophages plays a pivotal role in the development and pathogenesis of inflammatory disorders. RNA interference (RNAi) against the pro-inflammatory cytokine TNF-a offers a novel approach to precisely manipulate the immune system at a molecular and cellular level. However, therapeutic efficiency is impeded by siRNA degradation, minimal cellular delivery, and endosomal entrapment. We have recently developed nanoparticle-stabilized nanocapsules (NPSCs) for direct cytosolic siRNA delivery that facilitates siRNA translocation and avoids endosomal entrapment in vitro and in vivo. Using an LPS-induced inflammation model, we demonstrated high knockdown efficiency (~70%) of TNF-a secretion in serum by tail vein injection at a low siRNA dose of 0.28mg/kg. Therefore, this NPSCs system provides a new platform to significantly enhance the in vivo siRNA delivery efficiency for therapeutic applications.

Cytosolic siRNA delivery using nanoparticle-stabilized nanocapsules for in vivo anti-inflammatory therapy

256th National Meeting (2018)

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