title: cIBR effectively targets nanoparticles to LFA-1 on acute lymphoblastic T cells.
abstract: Leukocyte function associated antigen-1 (LFA-1) is a primary cell adhesion molecule of leukocytes required for mediating cellular transmigration into sites of inflammation via the vascular endothelium. A cyclic peptide, cIBR, possesses high affinity for LFA-1, and conjugation to the surface of poly(DL-lactic-co-glycolic acid) nanoparticles can specifically target and deliver the encapsulated agents to T cells expressing LFA-1. The kinetics of targeted nanoparticle uptake by acute lymphoblastic leukemia T cells was investigated by flow cytometry and microscopy and compared to untargeted nanoparticles. The specificity of targeted nanoparticles binding to the LFA-1 integrin was demonstrated by competitive inhibition using free cIBR peptide or using the I domain of LFA-1 to inhibit the binding of targeted nanoparticles. The uptake of targeted nanoparticles was concentration and energy dependent. The cIBR-conjugated nanoparticles did not appear to localize with lysosomes whereas untargeted nanoparticles were detected in lysosomes in 6 h and steadily accumulated in lysosomes for 24 h. Finally, T-cell adhesion to epithelial cells was inhibited by cIBR nanoparticles. Thus, nanoparticles displaying the cIBR ligand may offer a useful targeted drug delivery system as an alternative treatment of inflammatory diseases involving transmigration of leukocytes.
authors.affiliation: Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA.
authors.forename: Chuda
authors.initials: C
authors.lastname: Chittasupho
authors.forename: Prakash
authors.initials: P
authors.lastname: Manikwar
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Krise
authors.forename: Teruna J
authors.initials: TJ
authors.lastname: Siahaan
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland
mesh_terms: D001693:Biological Transport, Active; D002448:Cell Adhesion; D002449:Cell Aggregation; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D006801:Humans; D019344:Lactic Acid; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D053758:Nanoparticles / Q000737:chemistry; D010456:Peptides, Cyclic / Q000378:metabolism*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D054218:Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D013696:Temperature
chemical_list: D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D010456:Peptides, Cyclic; C515000:cIBR peptide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid