Peptide nanocarriers for targeted delivery of RNAi therapeutics
Although RNAi therapy is promising, siRNAs delivered in vivo face significant barriers including serum instability, renal excretion, and rapid uptake and clearance by the reticuloendothelial system (RES) [1,2]. Additionally, due to their large molecular weight and negative charge, naked siRNAs are unable to diffuse across the cellular membrane [3]. Many strategies using nanotechnology for siRNA delivery have been investigated to address these barriers, such as several classes of peptides. These peptides include cell penetrating peptides (CPPs), pH-sensitive membrane active peptides (PMAPs), and homing peptides [4-6], which mediate cellular uptake, membrane fusion/endosomal escape, and targeted delivery, respectively (Fig. 1). Although each class of peptides has been used individually to deliver siRNAs [7,8], few studies have combined different classes of peptides to overcome multiple barriers Therefore, our lab is developing tandem peptides containing several classes of peptide sequences and determining whether these peptides improve targeted delivery and uptake of bioactive siRNAs into tumor tissue.
References​
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