Peptide-containing aggregates as selective nanocarriers for therapeutics

被引：27

作者：

Accardo, Antonella ^{[1
]}

Tesauro, Diego ^{[1
]}

Aloj, Luigi ^{[3
]}

Tarallo, Laura ^{[3
]}

Arra, Claudio ^{[4
]}

Mangiapia, Gaetano ^{[2
]}

Vaccaro, Mauro ^{[2
]}

Pedone, Carlo ^{[1
]}

Paduano, Luigi ^{[2
]}

Morelli, Giancarlo ^{[1
]}

机构：

[1] Univ Naples Federico II, Dept Biol Sci & IBB CNR, CIRPeB, I-80134 Naples, Italy

[2] Univ Naples Federico II, Dept Chem, I-80126 Naples, Italy

[3] Fdn G Pascale, Ist Nazl Studio & Cura Tumori, Dept Nucl Med, I-80131 Naples, Italy

[4] Fdn G Pascale, Ist Nazl Studio & Cura Tumori, Dept Anim Experimentat, I-80131 Naples, Italy

来源：

CHEMMEDCHEM | 2008年 / 3卷 / 04期

关键词：

CCK8; peptide; drug delivery; dynamic light scattering; small angle neutron scattering; supramolecular aggregates;

D O I：

10.1002/cmdc.200700269

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

New nonocarriers ore 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-117 complexes linked to the some 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 similar to 40 angstrom and length >700 angstrom, open bilayer fragments with thickness similar to 65 angstrom, 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.

引用

页码：594 / 602

页数：9

共 42 条

[1] Physicochemical properties of mixed micellar aggregates containing CCK peptides and Gd complexes designed as tumor specific contrast agents in MRI [J].