| cIBR effectively targets nanoparticles to LFA-1 on acute lymphoblastic T cells. | |
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MedLine Citation:
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PMID: 19883077 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Chuda Chittasupho; Prakash Manikwar; Jeffrey P Krise; Teruna J Siahaan; Cory Berkland |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Molecular pharmaceutics Volume: 7 ISSN: 1543-8392 ISO Abbreviation: Mol. Pharm. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-02-01 Completed Date: 2010-04-19 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 101197791 Medline TA: Mol Pharm Country: United States |
Other Details:
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Languages: eng Pagination: 146-55 Citation Subset: IM |
Affiliation:
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Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Biological Transport, Active Cell Adhesion Cell Aggregation Cell Line, Tumor Drug Delivery Systems Humans Lactic Acid Ligands Lymphocyte Function-Associated Antigen-1 / metabolism* Lysosomes / metabolism Microscopy, Fluorescence Nanoparticles / chemistry Peptides, Cyclic / metabolism* Polyglycolic Acid Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / metabolism*, pathology T-Lymphocytes / metabolism*, pathology Temperature |
| Grant Support | |
ID/Acronym/Agency:
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P20 RR015563-060017/RR/NCRR NIH HHS; P20 RR015563-076485/RR/NCRR NIH HHS; P20 RR015563-086731/RR/NCRR NIH HHS; P20 RR016443/RR/NCRR NIH HHS; P20 RR016443-086923/RR/NCRR NIH HHS; P20 RR016443-096682/RR/NCRR NIH HHS; P20 RR016443-105872/RR/NCRR NIH HHS; R01 AI063002-01A1/AI/NIAID NIH HHS; R01 AI063002-02/AI/NIAID NIH HHS; R01 AI063002-03/AI/NIAID NIH HHS; R01 AI063002-04/AI/NIAID NIH HHS; R03 AR054035/AR/NIAMS NIH HHS; R03 AR054035-01A1/AR/NIAMS NIH HHS; R03 AR054035-02/AR/NIAMS NIH HHS; R03 AR054035-03/AR/NIAMS NIH HHS; T32 GM08359-11/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Ligands; 0/Lymphocyte Function-Associated Antigen-1; 0/Peptides, Cyclic; 0/cIBR peptide; 0/polylactic acid-polyglycolic acid copolymer; 26009-03-0/Polyglycolic Acid; 50-21-5/Lactic Acid |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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