Jump to main content
Jump to site search

Issue 8, 2013
Previous Article Next Article

How to optimize binding of coated nanoparticles: coupling of physical interactions, molecular organization and chemical state

Author affiliations

Abstract

One of the key challenges in the development of nano carriers for drug delivery and imaging is the design of a system that selectively binds to target cells. A common strategy is to coat the delivery device with specific ligands that bind strongly to overexpressed receptors. However such devices are usually unable to discriminate between receptors found on benign and malignant cells. We demonstrate, theoretically, how one can achieve enhanced binding to target cells by using multiple physical and chemical interactions. We study the effective interactions between a polymer decorated nano micelle or nanoparticle with three types of model lipid membranes that differ in the composition of their outer leaflet. They are: (i) lipid membranes with overexpressed receptors, (ii) membranes with a given fraction of negatively charged lipids and (iii) membranes with both overexpressed receptors and negatively charged lipids. The coating contains a mixture of two short polymers, one neutral for protection and the other a polybase with a functional end-group to optimize specific binding with the overexpressed receptors and electrostatic interactions with charged lipid head-groups. The strength of the binding for the combined system is much larger than the sum of the independent electrostatic or specific interactions binding. We find a range of distances where the addition of two effective repulsive interactions become an attraction in the combined case. The changes in the strength and shape of the effective interaction are due to the coupling that exists between molecular organization, physical interactions and chemical state, e.g., protonation. The predictions provide guidelines for the design of carrier devices for targeted drug and nanoparticle delivery and give insight in the competing and highly non-additive nature of the different effective interactions in nanoscale systems in constrained environments that are ubiquitous in synthetic and biological systems.

Graphical abstract: How to optimize binding of coated nanoparticles: coupling of physical interactions, molecular organization and chemical state

Back to tab navigation

Supplementary files

Publication details

The article was received on 27 Nov 2012, accepted on 18 Mar 2013 and first published on 05 Apr 2013


Article type: Paper
DOI: 10.1039/C3BM00181D
Citation: Biomater. Sci., 2013,1, 814-823
  •   Request permissions

    How to optimize binding of coated nanoparticles: coupling of physical interactions, molecular organization and chemical state

    R. J. Nap and I. Szleifer, Biomater. Sci., 2013, 1, 814
    DOI: 10.1039/C3BM00181D

Search articles by author

Spotlight

Advertisements