Journal
CHEMBIOCHEM
Volume 6, Issue 2, Pages 337-345Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.200400174
Keywords
drugs; iron; nanomaterials; particles; peptides
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We synthesized three peptides, a (D)-polyarginyl peptide (r8(FITC)), a Tat peptide (Tat(FITC)), and a control peptide (Cp(FITC)) and attached each to amino-CLIO, a nanoparticle 30 nm in diameter. We then examined the effective permeability, P-eff, of all six materials through CaCo-2 monoloyers. The transport of peptide-nanoparticles was characterized by a log phase (0-8 h) and a steady-state phase (9-27 h). The steady-state P-eff values for peptides were in the order r8(FITC) > Tat(FITC) = Cp(FITC). When r8(FITC) and Tat(FITC) peptides were attached to the nanoparticle, they conferred their propensity to traverse cell monolayers onto the nanoparticle, whereas Cp(FITC) did not. Thus, when the r8(FITC) peptide was attached to the amino-CLIO nanoparticle, the resulting peptide-nanoparticle had a P-eff similar to that of this poly-(D)-arginyl peptide alone. The P-eff of r8(FITC)-CLIO (Mwsimilar to1000 kDa) was similar to that of mannitol (Mw = 182 Da), a poorly transported reference substance, with a far lower molecular weight. These results are the first to indicate that the modification, of nanoparticles by attachment of membrane-translocating sequence-based peptides can alter nanoparticle transport through monolayers. This suggests that the surface modification of nanoparticles might be a general strategy for enhancing the permeability of drugs and that high-permeability nanoparticle-based therapeutics can be useful in selected pharmaceutical applications.
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