An immobilized nanoparticle-based platform for efficient gene knockdown of targeted cells in the circulation.
It is well established that specific interaction between adhesion molecules of endothelial cells and receptors on leukocytes can separate and recruit leukocytes from the bloodstream to sites of inflammation and coagulation. Previously, we showed that P-selectin can be absorbed onto the surface of a blood-compatible microrenathane tube, and the P-selectin-coated surface could successfully capture P-selectin receptor-positive stem cells from physiological shear flow in vitro and from the bloodstream in vivo. In this paper, P-selectin was covalently attached to the surface of nanoscale liposomes to create targeting nanoparticles (NPs). Small interfering RNA (siRNA) was encapsulated by these nanoscale liposomes, and the liposomes were stabilized by PEGylation with DSPE-PEG2000. Experiments showed that these P-selectin-, PEGylated-, nanoscale-liposomes (PS-DSPE-PEG NPs) could be absorbed onto the inner surface of microrenathane tubing. The coated surface could specifically capture targeted cells from physiological shear flow, efficiently deliver encapsulated siRNA into adherent cells and dramatically silence the targeted gene neutrophil elastase. With this device, we create a high localized concentration for siRNA delivery in the circulatory system, providing circulating target cells adequate time to interact with therapeutic materials. SiRNA is efficaciously delivered into specific target cells, thereby providing a powerful tool for highly efficient siRNA transfection and other therapeutic materials delivery in circulation. The method should prove especially useful for diseases derived from disorders of blood cells.
Huang
Z
Z
Department of Biomedical Engineering, Cornell University, Ithaca, NY, USA.
King
M R
MR
D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D018390:Gene Targeting; D006098:Granulocytes / Q000378:metabolism; D018922:HL-60 Cells; D018056:Hemorheology / Q000502:physiology; D006801:Humans; D019272:Leukocyte Elastase / Q000235:genetics / Q000378:metabolism; D008081:Liposomes; D053758:Nanoparticles; D019007:P-Selectin / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured
D008081:Liposomes; D019007:P-Selectin; D034741:RNA, Small Interfering; D019272:Leukocyte Elastase