ICAM-1 targeting of doxorubicin-loaded PLGA nanoparticles to lung epithelial cells.

ICAM-1 targeting of doxorubicin-loaded PLGA nanoparticles to lung epithelial cells.
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DOI:
10.1016/j.ejps.2009.02.008
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发表时间:
2009-05-12
影响因子:
4.6
通讯作者:
Berkland, Cory J.
Berkland, Cory J.
中科院分区:
医学2区
文献类型:
--
作者:
Chittasupho, Chuda;Xie, Sheng-Xue;Baoum, Abdulgader;Yakovleva, Tatyana;Siahaan, Teruna J.;Berkland, Cory J.

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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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