title: In vivo performance of polymer nanocarriers dually-targeted to epitopes of the same or different receptors.
abstract: Modification of drug delivery nanomaterials with affinity molecules that facilitate targeting, has rendered a new class of ligands for cell receptors, which often possess valency and dimensions different from natural counterparts. Designing strategies to target multiple receptors or, never explored, multiple epitopes on the same receptor may modulate the biodistribution properties of these nanomaterials. We examined this using antibody-directed targeting of polymer nanocarriers to transferrin receptor (TfR) and intercellular adhesion molecule 1 (ICAM-1). Regarding epitopes on one receptor, nanocarriers addressed with anti-TfR-R17 maintained brain and lung targeting in mice, compared with "free" antibody, while anti-TfR-8D3 nanocarriers lost specificity. Coating nanocarriers with both antibodies decreased targeting in brain and liver, not lungs, modulating biodistribution. Regarding different receptors, nanocarriers coated with both anti-ICAM and anti-TfR displayed intermediate specific accumulation in lungs and higher in liver, compared to single-targeted nanocarriers, while brain targeting was comparable to TfR- and lower than ICAM-1-targeted nanocarriers. Tracing a model therapeutic cargo, acid sphingomyelinase (enzyme replacement for Niemann-Pick Disease A-B), showed that combined-targeted anti-ICAM/TfR nanocarriers enhanced enzyme delivery versus "free" enzyme, with biodistribution patterns different from single-targeted nanocarriers. Hence, targeting nanocarriers to multiple epitopes or receptors holds promise to control distribution of drug delivery nanomaterials in the body.
authors: Fischell Department of Bioengineering, School of Engineering, University of Maryland, College Park, MD 20742, USA.
authors: Iason T
authors: IT
authors: Papademetriou
authors: Carmen
authors: C
authors: Garnacho
authors: Edward H
authors: EH
authors: Schuchman
authors: Silvia
authors: S
authors: Muro
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems; D000939:Epitopes / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D009928:Organ Specificity / Q000187:drug effects; D011108:Polymers / Q000737:chemistry*; D011990:Receptors, Transferrin / Q000378:metabolism*; D013108:Sphingomyelin Phosphodiesterase / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000906:Antibodies; D004337:Drug Carriers; D000939:Epitopes; D011108:Polymers; D011990:Receptors, Transferrin; D018799:Intercellular Adhesion Molecule-1; D013108:Sphingomyelin Phosphodiesterase
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