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ICAM-1 Targeting of Doxorubicin-Loaded PLGA Nanoparticles to Lung Epithelial Cells
Chittasupho, Chuda Xie, Sheng-Xue Baoum, Abdulgader Ahmed Yakovleva, Tatyana Siahaan, Teruna J. Berkland, Cory J.
Chittasupho, Chuda
Xie, Sheng-Xue
Baoum, Abdulgader Ahmed
Yakovleva, Tatyana
Siahaan, Teruna J.
Berkland, Cory J.
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Abstract
Interaction of leukocyte function associated antigen-1 (LFA-1) on T-lymphoctytes and intercellular adhesion molecule-1 (ICAM-1) on epithelial cells controls leukocyte adhesion, spreading, and extravasation. This process plays an important role in leukocyte recruitment to a specific site of inflammation and has been indentified as a biomarker for certain types of carcinomas. Cyclo-(1,12)-PenITDGEATDSGC (cLABL) has been shown to inhibit LFA-1 and ICAM-1 interaction via binding to ICAM-1. In addition, cLABL has been shown to internalize after binding ICAM-1. The possibility of using cLABL conjugated nanoparticles (cLABL-NP) as a targeted and controlled release drug delivery system has been investigated in this study. The cLABL peptide was conjugated to a modified Pluronic® surfactant on poly (DL-lactic-co-glycolic acid) (PLGA) nanoparticles. The cLABL-NP showed more rapid cellular uptake by A549 lung epithelial cells compared to nanoparticles without peptide. The specificity of ICAM-1 mediated internalization was confirmed by blocking the uptake of cLABL-NP to ICAM-1 using free cLABL peptide to block the binding of cLABL-NP to ICAM-1 on the cell surface. Cell studies suggested that cLABL-NPs targeted encapsulated doxorubicin to ICAM-1 expressing cells. Cytotoxicity assay confirmed the activity of the drug incorporated in nanoparticles. Sustained release of doxorubicin afforded by PLGA nanoparticles may enable cLABL-NP as a targeted, controlled release drug delivery system.
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2010-05-12
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Elsevier
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berkland_targeting.pdf
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ICAM-1, PLGA, Nanoparticles, Targeting
Citation
Chittasupho, Chuda, Sheng-Xue Xie, Abdulgader Baoum, Tatyana Yakovleva, Teruna J. Siahaan, and Cory J. Berkland. "ICAM-1 Targeting of Doxorubicin-loaded PLGA Nanoparticles to Lung Epithelial Cells." European Journal of Pharmaceutical Sciences 37.2 (2009): 141-50.