title: Exploiting shape, cellular-hitchhiking and antibodies to target nanoparticles to lung endothelium: Synergy between physical, chemical and biological approaches.
abstract: Delivery of nanoparticles to target specific tissues remains a challenge due to their rapid removal from circulation by the reticuloendothelial (RES) system. The majority of past research has addressed this issue via chemical modification of nanoparticles in the form of hydrophilic coatings which reduces adsorption of opsonins that trigger RES clearance. Recently, additional approaches have been developed which leverage the natural mechanisms our own circulatory cells use to avoid immune system clearance. One such method, called 'cellular-hitchhiking', accomplishes this by non-covalent attachment of nanoparticles to the surface of red blood cells. Concomitantly, approaches that make use of modified nanoparticle geometry, that is rod-shaped nanoparticles, have also been used to avoid immune system clearance and improve tissue targeting. Here, we systematically investigate three approaches and their combinations to improve lung targeting while avoiding RES clearance. Our results show that an approach that combines targeting antibodies (anti-ICAM-1), rod-shaped particles and cellular hitchhiking into one delivery system effectively lowered the accumulated concentration of nanoparticles in RES organs by over two-fold as compared to any other combination or single method, while simultaneously increasing the concentration of accumulated nanoparticles in the lungs from 1.2 to 8.9 fold. The strategy described here offers a novel means that combine chemical, physical and biological approaches to maximize tissue targeting.
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA 93106, USA.
authors.forename: Aaron C
authors.initials: AC
authors.lastname: Anselmo
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA 93106, USA.
authors.forename: Sunny
authors.initials: S
authors.lastname: Kumar
authors.affiliation: School of Pharmacy, Keck Graduate Institute, 535 Watson Dr., Claremont, CA 91711, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA 93106, USA.
authors.forename: Austin M
authors.initials: AM
authors.lastname: Pearce
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA 93106, USA.
authors.forename: Analisa
authors.initials: A
authors.lastname: Ragusa
authors.affiliation: Department of Pharmacology and Center for Translational Targeted Therapeutics and Nanomedicine, Perelman School of Medicine, University of Pennsylvania, USA.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Muzykantov
authors.affiliation: Department of Chemical Engineering, Center for Bioengineering, University of California, Santa Barbara, CA 93106, USA. Electronic address: samir@engineering.ucsb.edu.
authors.forename: Samir
authors.initials: S
authors.lastname: Mitragotri
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology*; D002478:Cells, Cultured; D004727:Endothelium / Q000737:chemistry / Q000276:immunology*; D004912:Erythrocytes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology*; D008168:Lung / Q000737:chemistry* / Q000276:immunology; D008422:Materials Testing; D051379:Mice; D008807:Mice, Inbred BALB C; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D009928:Organ Specificity; D010316:Particle Size; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1
keywords: Cell-mediated drug delivery; Cellular hitchhiking; Erythrocytes; Nanoparticles; Red blood cells; Shape