Peptide-containing aggregates as selective nanocarriers for therapeutics

Antonella Accardo, Diego Tesauro, Luigi Aloj, Laura Tarallo, Claudio Arra, Gaetano Mangiapia, Mauro Vaccaro, Carlo Pedone, Luigi Paduano, Giancarlo Morelli

Research output: Contribution to journalArticle

Abstract

New nanocarriers are obtained by assembling two amphiphilic monomers: one containing the bioactive peptide CCK8 spaced, by a polydisperse poly(ethylene glycol), from two hydrophobic tails ((C18)2PEG2000CCK8), and the other containing a chelating agent able to give stable radiolabeled indium-111 complexes linked to the same hydrophobic moiety ((C18)2DTPAGlu). The size and shape of the supramolecular aggregates were structurally characterized by dynamic light scattering, small-angle neutron scattering, and cryogenic transmission electronic microscopy. Under the experimental conditions we investigated (pH 7.4 and molar ratio between monomers 30:70), there is the presence of high polydisperse aggregates: rod-like micelles with a radius of ∼40 Å and length >700 Å, open bilayer fragments with thickness ∼65 Å, and probably vesicles. The presence of the bioactive peptide well exposed on the external surface of the aggregate allows selective targeting of nanocarriers towards the cholecystokinin receptors overexpressed by the cancerous cells. In vitro binding assays and in vivo biodistribution studies by nuclear medicine experiments using indium-111 are reported. Moreover, preliminary data concerning the drug loading capability of the aggregates and their drug efficiency on the target cells is reported by using the cytotoxic drug doxorubicin. Incubation of receptor-positive and control cells with peptide-containing aggregates filled with doxorubicin shows significantly lower cell survival in receptor-expressing cells relative to the control, for samples incubated in the presence of doxorubicin.

Original languageEnglish
Pages (from-to)594-602
Number of pages9
JournalChemMedChem
Volume3
Issue number4
DOIs
Publication statusPublished - Apr 14 2008

Keywords

  • CCK8 peptide
  • Drug delivery
  • Dynamic light scattering
  • Small angle neutron scattering
  • Supramolecular aggregates

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry
  • Molecular Medicine

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  • Cite this

    Accardo, A., Tesauro, D., Aloj, L., Tarallo, L., Arra, C., Mangiapia, G., Vaccaro, M., Pedone, C., Paduano, L., & Morelli, G. (2008). Peptide-containing aggregates as selective nanocarriers for therapeutics. ChemMedChem, 3(4), 594-602. https://doi.org/10.1002/cmdc.200700269