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Direct Protein Delivery to Mammalian Cells Using Cell-permeable Cys2-His2 Zinc-finger Domains
Published on: March 25, 2015
Targeted drug delivery utilizing protein-like molecular architecture
Evonne M Rezler1, David R Khan, Janelle Lauer-Fields
1Department of Chemistry and Biochemistry, Florida Atlantic University, 777 Glades Road, Boca Raton, Florida 33431, USA.
Journal of the American Chemical Society
|April 3, 2007
Summary
Targeted liposomes using peptide-amphiphiles show promise for drug delivery. These nanotechnology-based drug delivery systems (nanoDDSs) selectively target CD44/chondroitin sulfate proteoglycan (CSPG) receptors on metastatic melanoma cells.
Area of Science:
- Biotechnology and Nanomedicine
- Materials Science
- Cell Biology
Background:
- Nanotechnology-based drug delivery systems (nanoDDSs) offer enhanced physical, chemical, and biological properties for targeted therapies.
- CD44/chondroitin sulfate proteoglycan (CSPG) receptors are overexpressed in metastatic melanoma, presenting a target for selective drug delivery.
- The binding sequence of CD44/CSPG within type IV collagen has been identified, enabling targeted ligand design.
Purpose of the Study:
- To construct and evaluate peptide-amphiphile (PA)-functionalized liposomes for targeted delivery to CD44/CSPG receptors.
- To investigate the influence of liposome lipid composition on stability and targeting efficiency.
- To assess the cellular uptake and targeting specificity of PA-liposomes in metastatic melanoma and fibroblast cell lines.
Main Methods:
- Synthesis of a triple-helical peptide-amphiphile (alpha1(IV)1263-1277 PA) designed to bind CD44/CSPG.
- Incorporation of alpha1(IV)1263-1277 PA into liposomes with varying lipid compositions (DSPC, DPPC, DSPG, DLPC, cholesterol).
- Evaluation of liposome stability, cellular fluorophore delivery, and receptor-mediated uptake through competitive inhibition assays.
Main Results:
- Liposomes composed of DSPC, DSPG, and cholesterol exhibited greater stability compared to those with DPPC.
- The alpha1(IV)1263-1277 PA enhanced the stability of DPPC liposomes and demonstrated selective fluorophore delivery to CD44/CSPG-expressing cells.
- Targeting specificity was confirmed by a dose-dependent decrease in fluorophore delivery upon pre-incubation with exogenous alpha1(IV)1263-1277.
Conclusions:
- Peptide-amphiphile targeted liposomes can be rationally designed and fine-tuned for drug delivery applications.
- Liposome lipid composition significantly impacts system stability and performance.
- alpha1(IV)1263-1277 PA liposomes show potential as targeted nanoDDSs for CD44/CSPG-positive metastatic melanoma.
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