RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation.
Int J Nanomedicine
; 6: 3113-23, 2011.
Article
em En
| MEDLINE
| ID: mdl-22238505
ABSTRACT
Rosette nanotubes (RNT) are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (Gâ§C motif). In this report, the Gâ§C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-Gâ§C) and amino acid Lys (K-Gâ§C) which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as K(x)/RGDSK(y)-RNT, where x and y refer to the molar ratios of K-Gâ§C and RGDSK-Gâ§C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous K(x)/RGDSK(y)-RNT on acute lipopolysaccharide (LPS)-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 µg and/or intravenously with K9°/RGDSK¹°-RNT. Here we provide the first evidence that intravenous administration of K9°/RGDSK¹°-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K9°/RGDSK¹°-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K9°/RGDSK¹°-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1ß, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K9°/RGDSK¹°-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
Pneumonia
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Lipopolissacarídeos
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Nanotubos
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article