TY - JOUR
T1 - How to optimize binding of coated nanoparticles
T2 - Coupling of physical interactions, molecular organization and chemical state
AU - Nap, R. J.
AU - Szleifer, I.
PY - 2013/8
Y1 - 2013/8
N2 - 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.
AB - 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.
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U2 - 10.1039/c3bm00181d
DO - 10.1039/c3bm00181d
M3 - Article
AN - SCOPUS:84885332263
SN - 2047-4830
VL - 1
SP - 814
EP - 823
JO - Biomaterials Science
JF - Biomaterials Science
IS - 8
ER -