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Published on: April 23, 2017
PLGA nanoparticle--peptide conjugate effectively targets intercellular cell-adhesion molecule-1.
Na Zhang1, Chuda Chittasupho, Chadarat Duangrat
1Departments of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, USA.
Bioconjugate Chemistry
|November 14, 2007
Summary
Targeted nanoparticles using cLABL peptide efficiently bind to cells expressing ICAM-1. This peptide-mediated targeting enhances nanoparticle uptake, offering potential for localized drug delivery to inflammatory sites.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cell Biology
Background:
- Targeted drug delivery enhances therapeutic efficacy and reduces side effects by localizing agents to specific tissues.
- Antibodies and peptides are explored for targeting drug-loaded nanoparticles, with peptides offering a stable and cost-effective alternative.
- Intercellular cell-adhesion molecule-1 (ICAM-1) is upregulated on cells in inflammatory sites.
Purpose of the Study:
- To evaluate the targeting capability of cyclo(1,12)PenITDGEATDSGC (cLABL) peptide-conjugated nanoparticles to human umbilical cord vascular endothelial cells (HUVECs) with upregulated ICAM-1.
- To assess the specificity and efficiency of peptide-mediated nanoparticle binding and cellular uptake.
- To explore the potential of cLABL peptide-targeted nanoparticles for therapeutic applications in inflammatory conditions.
Main Methods:
- Conjugation of poly( dl-lactic-coglycolic acid) (PLGA) nanoparticles with polyethylene glycol (PEG) and cLABL peptide.
- Upregulation of ICAM-1 expression on HUVEC monolayers using interferon-gamma.
- Assessment of nanoparticle binding via preincubation with free peptide to confirm ICAM-1 specificity.
- Evaluation of nanoparticle endocytosis and lysosomal trafficking compared to untargeted nanoparticles.
Main Results:
- cLABL-conjugated PLGA-PEG nanoparticles demonstrated rapid binding to HUVECs with upregulated ICAM-1.
- Nanoparticle binding was specifically mediated by the cLABL peptide's interaction with ICAM-1, as confirmed by blocking experiments.
- Targeted nanoparticles showed enhanced endocytosis and lysosomal trafficking compared to untargeted nanoparticles.
Conclusions:
- The cLABL peptide effectively targets nanoparticles to HUVECs expressing ICAM-1.
- Peptide-mediated targeting enhances nanoparticle uptake and intracellular trafficking.
- This approach holds promise for targeted delivery of therapeutics to inflammatory sites characterized by ICAM-1 upregulation.
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