Delivery of siRNA to Endothelial Cells In Vivo Using Lysine/Histidine Oligopeptide-Modified Poly(β-amino ester) Nanoparticles

Nanobiotechnology approaches for cardiovascular diseases: site-specific targeting of drugs and nanoparticles for atherothrombosis

“…To overcome the interaction of NPs with serum lipoproteins and their passive accumulation in the liver, Dosta et al developed a series of oligopeptide-modified poly-beta-amino ester (pBAE) NPs to deliver small interfering RNA (siRNA) against ICAM-2 in vivo [ 87 ]. The group chose pBAE because it is a biodegradable and biocompatible polymer that can penetrate cell membranes easily [ 88 ].…”

Nanoparticles: Promising Tools for the Treatment and Prevention of Myocardial Infarction

“… LV posterior wall and LV mass; Collagen deposition ↓; Angiogenesis↑; TNFα↓, TGF-β and Socs1↑ [ 124 ] PFBT core with a DSPE-PEG shell, conjugated with CPP ~110nm miR-199a-3p Rats; I/R (ligation for 1h) Peri-infarct area injection; in shear-thinning hydrogel EF↑; preserved LVESV; Scar size↓; Angiogenesis↑; Proliferation of CMs↑; Expression of HIF1α↑ [ 125 ] Poly(amidoamine)-histidine 60nm miR-214-3p, miR-194-5p, antagomiR-122-5p H9c2 and primary cultured CMs Expression levels of Bax, Bad, Caspase 3 and Caspase 9↓; Apoptosis↓; Cell viability↑ [ 127 ] siRNA/ antisense oligonucleotide delivery system Dendrigraft poly-L-lysine, decored with AT1R-targeting peptide, and PEGylated ~200nm Anti-miR-1 antisense oligonucleotide Mice; LAD i.v. Infarct size↓(Masson-Trichrome) [ 130 ] PMSNs, combined with PEI 100–200nm CCR2 siRNA Mice; LAD Combined therapy: intramyocardial injection (MSCs) and i.v. (NPs) Infarct size↓; Angiogenesis↑; Ly6C high monocytes/CD11b-positive monocytes↓ No obvious toxicity [ 131 ] A polymer–lipid hybrid material, combined with PEG–lipid conjugates 60–80nm siSdf1, siMcp1 Mice; LCA after 10-week high-fat diet i.v.…”

“…Dosta and colleagues demonstrated that poly(β-amino ester) particles modified by adding lysine-/histidine-oligopeptides could represent a system for the transfer of siRNA. 130 Studies have now revealed that chemokine C–C motif ligand 2 (CCL2) and its cognate receptor C–C chemokine receptor 2 (CCR2) promoted excessive Ly6C high inflammatory monocyte infiltration in infarcted area and aggravate myocardial injury. 131 Photoluminescent mesoporous silicon nanoparticles (MSNPs) carrying siCCR2 have been reported to improve the effectiveness of transplanted mesenchymal stem cells (MSCs) in reducing myocardial remodeling after acute MI.…”

Special Issue on Professor John M. Tarbell’s Contribution to Cardiovascular Engineering

“…ZHANG ET AL. 41 9 Endothelial cell dysfunction plays a critical role in atherosclerotic and pulmonary diseases and cancer. Here, the authors developed the lysine-/histidine-oligopeptide modified pBAE (C6-KH) nanoparticle carrying siRNAs, which was able to specifically knockdown ICAM2 in endothelial cells both in cultured mouse aortic endothelial cells in vitro and mouse artery in vivo.…”

“…Using the mouse brain microvascular endothelial cells (bEnd3 cells), they found that positively charged nanoparticles (20-100 nm diameter) show favorable transcellular permeability, due in part to the negative charge of the surface glycocalyx of the BBB. Their predictive model for nanoparticle size and charge should be helpful in developing optimal drug delivery strategy across BBB.DOSTA ET AL 9. DELIVERY OF SIRNA TO ENDOTHELIAL CELLS IN VITRO USING LYS/HIS OLIGOPEPTIDE-MODIFIED POLY(B-AMINO ESTER) NANOPARTICLE Hanjoong Jo, Professor at Emory University and Georgia Tech, was co-mentored by Professors John Tarbell and Ted Hollis at Penn State.…”