Issue 6, 2015

A lipopolysaccharide binding heteromultivalent dendrimer nanoplatform for Gram negative cell targeting

Abstract

We report on the practicality of a heteromultivalent design strategy for a nanoplatform that targets lipopolysaccharide molecules (LPS) present on the surface of Gram-negative bacteria. This design is based on the conjugation of a poly(amido amine) (PAMAM) dendrimer with two types of ligands, each having distinct affinities: (i) polymyxin B (PMB) as a primary high affinity ligand; (ii) a PMB-mimicking dendritic branch as an auxiliary low affinity ligand. Co-conjugation of these two ligands maximizes the efficiency of the primary ligand even when the primary ligand is present at a low valency on the nanoplatform (mean nPMB ≈ 1). By performing surface plasmon resonance studies using a LPS-immobilized cell wall model, we identified an ethanolamine (EA)-terminated branch as the auxiliary ligand that promotes binding avidity via heteromultivalent association. PMB conjugation of the dendrimer with excess EA branches led to LPS avidity two orders of magnitude greater than unconjugated PMB. Such tight binding observed by SPR corresponded well with adsorption to E. coli cells and with potent bactericidal activity in vitro.

Graphical abstract: A lipopolysaccharide binding heteromultivalent dendrimer nanoplatform for Gram negative cell targeting

Supplementary files

Article information

Article type
Paper
Submitted
12 Oct 2014
Accepted
15 Dec 2014
First published
18 Dec 2014

J. Mater. Chem. B, 2015,3, 1149-1156

Author version available

A lipopolysaccharide binding heteromultivalent dendrimer nanoplatform for Gram negative cell targeting

P. T. Wong, S. Tang, K. Tang, A. Coulter, J. Mukherjee, K. Gam, J. R. Baker and S. K. Choi, J. Mater. Chem. B, 2015, 3, 1149 DOI: 10.1039/C4TB01690D

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements