Spatially controlled assembly of affinity ligand and enzyme cargo enables targeting ferritin nanocarriers to caveolae. (December 2018)

• Record Type: Journal Article
• Authors: Shuvaev, Vladimir V.; Khoshnejad, Makan; Pulsipher, Katherine W.; Kiseleva, Raisa Yu.; Arguiri, Evguenia; Cheung-Lau, Jasmina C.; LeFort, Kathleen M.; Christofidou-Solomidou, Melpo; Stan, Radu V.; Dmochowski, Ivan J.; Muzykantov, Vladimir R.
• Is Part Of: Biomaterials. Volume 185(2018)
• Page Start: 348
• Page End: 359
• Publication Date: 2018-12
• Subjects: Ferritin nanocage -- Protein nanoparticle -- Superoxide dismutase -- Endothelial targeting -- Inflammation; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2018.09.015
• Languages: English
• ISSNs: 0142-9612

Abstract

Abstract: One of the goals of nanomedicine is targeted delivery of therapeutic enzymes to the sub-cellular compartments where their action is needed. Endothelial caveolae-derived endosomes represent an important yet challenging destination for targeting, in part due to smaller size of the entry aperture of caveolae (ca. 30–50 nm). Here, we designed modular, multi-molecular, ferritin-based nanocarriers with uniform size (20 nm diameter) for easy drug-loading and targeted delivery of enzymatic cargo to these specific vesicles. These nanocarriers targeted to caveolar Plasmalemmal Vesicle-Associated Protein (Plvap) deliver superoxide dismutase (SOD) into endosomes in endothelial cells, the specific site of influx of superoxide mediating by such pro-inflammatory signaling as some cytokines and lipopolysaccharide (LPS). Cell studies showed efficient internalization of Plvap-targeted SOD-loaded nanocarriers followed by dissociation from caveolin-containing vesicles and intracellular transport to endosomes. The nanocarriers had a profound protective anti-inflammatory effect in an animal model of LPS-induced inflammation, in agreement with the characteristics of their endothelial uptake and intracellular transport, indicating that these novel, targeted nanocarriers provide an advantageous platform for caveolae-dependent delivery of biotherapeutics.