A Poly(Propyleneimine) Dendrimer ‐Based Polyplex‐System for Single‐Chain Antibody‐Mediated Targeted Delivery and Cellular Uptake of SiRNA

This study reports a new modular polyplex carrier system for targeted delivery of siRNA, which is based on transfection‐disabled maltose‐modified poly(propyleneimine)‐dendrimers (mal‐PPI) bioconjugated to single chain fragment variables (scFvs). To achieve targeted delivery into tumor cells expressing the epidermal growth factor receptor variant III (EGFRvIII), monobiotinylated anti‐EGFRvIII scFv fused to a Propionibacterium shermanii transcarboxylase‐derived biotinylation acceptor (P‐BAP) is bioconjugated to mal‐PPI through a novel coupling strategy solely based on biotin–neutravidin bridging. In contrast to polyplexes containing an unspecific control scFv‐P‐BAP, the generated EGFRvIII‐specific polyplexes are able to exclusively deliver siRNA to tumor cells and tumors by receptor‐mediated endocytosis. These results suggest that receptor‐mediated uptake of otherwise noninternalized mal‐PPI‐based polyplexes is a promising avenue to improve siRNA therapy of cancer, and introduce a novel strategy for modular bioconjugation of protein ligands to nanoparticles. Polyplexes for targeted delivery of small interfering RNAs (siRNA) to target cells are created by conjugation of transfection‐disabled maltose‐modified poly(propyleneimine) and monobiotinylated single chain antibodies to neutravidin and complexation with siRNA macromolecules at defined stoichiometry. Targeted delivery of siRNA by polyplexes to cells and tumor xenografts is dependent on r...
Source: Small - Category: Nanotechnology Authors: Tags: Full Paper Source Type: research