Polyion Complex Micelles with Protein-Modified Corona for Receptor-Mediated Delivery of Oligonucleotides into Cells

• DOI: 10.1021/bc990037c
• Publication Date: 2002-07-26T05:34:22Z
• Authors: Serguei Vinogradov; Elena Batrakova; Shu Li; Alexander Kabanov
• Keywords: Avidin; Streptavidin; Conjugate; Transferrin receptor

Graft-copolymers, containing poly(ethylene glycol) (PEG) and polyethyleneimine (PEI) chains have been proposed as carriers for delivery of phosphorothioate oligonucleotides (SODNs). Complexes such copolymers with SODN self-assemble into particles having a core neutralized PEI corona PEG. Transferrin molecules are attached to the PEG using avidin/biotin construct. For this purpose, biotin moieties covalently linked free ends in PEG-g-PEI copolymer. SODNs reacted mixtures biotinylated biotin-free various compositions adjust number complex. Resulting complexes small size (ca. 40 nm) do not aggregate aqueous solutions at least several days. To attach transferrin, they supplemented first avidin then biotin−transferrin conjugate. This increases effective diameter ca. 75−103 nm, depending on composition Cellular accumulation fluorescence microscopy studies characterize effects these modifications interaction fluorescently labeled KBv cell monolayers. The data suggest significant enhancement association cells resulting from modification complex transferrin. complimentary site 546−565 human mdr 1-mRNA was used inhibit expression drug efflux transporter, P-glycoprotein (P-gp), multiple resistant (MDR) cancer (KBv, MCF-7 ADR). Accumulation P-gp specific probe, rhodamine 123, monolayers is system following treatment antisense or its complexes. study suggests that incorporated retain ability system, while randomized control inactive. Therefore, released interacts intracellular target upon cells. Furthermore, transferrin leads increase Overall, polyion micelles protein-modified promising tools SODN.