ICAM-1 targeting of doxorubicin-loaded PLGA nanoparticles to lung epithelial cells.
Interaction of leukocyte function associated antigen-1 (LFA-1) on T-lymphocytes 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 identified 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.
Chittasupho
Chuda
C
Department of Pharmaceutical Chemistry, School of Pharmacy, The University of Kansas, Lawrence, KS 66047, USA.
Xie
Sheng-Xue
SX
Baoum
Abdulgader
A
Yakovleva
Tatyana
T
Siahaan
Teruna J
TJ
Berkland
Cory J
CJ
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D004317:Doxorubicin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008168:Lung / Q000166:cytology / Q000378:metabolism*; D053758:Nanoparticles
D000970:Antineoplastic Agents; D018799:Intercellular Adhesion Molecule-1; D004317:Doxorubicin