RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation

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 (GwedgeC motif). In this report, the GwedgeC motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-GwedgeC) and amino acid Lys (K-GwedgeC) 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-GwedgeC and RGDSK-GwedgeC, 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 mug and/or intravenously with K(9)(0)/RGDSK(1)(0)-RNT. Here we provide the first evidence that intravenous administration of K(9)(0)/RGDSK(1)(0)-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K(9)(0)/RGDSK(1)(0)-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 K(9)(0)/RGDSK(1)(0)-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1beta, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K(9)(0)/RGDSK(1)(0)-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.