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Transport of surface-modified nanoparticles through cell monolayers
Annette M Koch1, Fred Reynolds, Hans P Merkle
1Department of Chemistry and Applied BioSciences, Drug Formulation and Delivery, Swiss Federal Institute of Technology Zürich (ETH Zürich), Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Chembiochem : a European Journal of Chemical Biology
|January 15, 2005
Summary
Attaching cell-penetrating peptides to nanoparticles significantly enhances their transport across cell layers. This surface modification strategy shows promise for improving drug delivery and nanoparticle-based therapeutics.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Cell Biology
Background:
- Nanoparticles offer potential for drug delivery but often face challenges in cellular transport.
- Surface modification of nanoparticles can alter their interaction with biological barriers.
- Membrane-translocating sequences (MTS) are peptides known to facilitate cellular uptake.
Purpose of the Study:
- To investigate if attaching MTS peptides to nanoparticles can enhance their permeability across cell monolayers.
- To compare the transport of peptide-functionalized nanoparticles with bare nanoparticles and free peptides.
Main Methods:
- Synthesis of three peptides: a D-polyarginyl peptide (r8), a Tat peptide, and a control peptide (Cp), each labeled with FITC.
- Attachment of these peptides to amino-functionalized superparamagnetic iron oxide nanoparticles (CLIO, 30 nm diameter).
- Measurement of effective permeability (Peff) of peptides, nanoparticles, and peptide-nanoparticle conjugates across CaCo-2 cell monolayers.
Main Results:
- Peptide-nanoparticle transport exhibited a lag phase (0-8 h) followed by a steady-state phase (9-27 h).
- The r8 peptide and Tat peptide, when attached to nanoparticles, conferred their high permeability characteristics to the nanoparticles.
- The r8(FITC)-CLIO nanoparticle demonstrated a Peff comparable to the free r8(FITC) peptide and similar to mannitol, despite a much higher molecular weight.
Conclusions:
- Surface modification of nanoparticles with MTS peptides can significantly enhance their transport across cell monolayers.
- This strategy represents a general approach for improving nanoparticle permeability for drug delivery applications.
- High-permeability nanoparticle-based therapeutics could be valuable in specific pharmaceutical contexts.