Table 1.

Physiological barriers in siRNA delivery by intravenous injection.

Barrier	Approach
Degradation by RNAses	Chemical modification of siRNAs, inclusion of siRNAs in NP-based delivery systems
Renal clearance	Inclusion of the siRNA in a nanocomplex with a HD >6 nm
Reticuloendothelial system	Addition of PEG to the nanocomplex to reduce protein corona formation and phagocytosis
Limited access into tumor tissue	Passive accumulation: limit NP size (<200 nm) to promote the EPR effect. Active targeting: Inclusion of a targeting ligand on the surface of the NPs