One of the key challenges in nanoscience/medicine is to design carrier system for drug delivery or imaging that selectively binds to target cells without binding to healthy cells. A common strategy is to end-functionalize the polymers coating of 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 selective binding to target cells by using multiple physical and chemical interactions. We study the effective interactions between a polymer decorated nanosized micelle or solid nanoparticle with model lipid layers. The polymer coating contains a mixture of two polymers, one neutral (e.g., polyethylene glycol) for protection and the other a polybase with a functional end-group to optimize specific binding and electrostatic interactions with the charged lipid head-groups found on the lipid surface. The strength of the binding for the combined system is much larger than the sum of the independent electrostatic or specific ligand-receptor binding. Moreover, it is found that the molecular organization of the polymer coating is qualitatively different in the combined system. This is manifested in the strength of the binding and also in a regime of distances where the addition of two repulsions leads to an attraction. The search for optimal binding conditions lead to the finding of the non-trivial and highly non-additive coupling that exists in systems where chemical equilibrium, like acid-base reactions and ligand-receptor binding, molecular organization, and physical interactions are coupled together. The theoretical predictions not only provide practical guidelines for the design of polymeric carrier devices for targeted drug delivery, they also give fundamental physical insight in the competing and non-additive nature of the coupling between different forces found in inhomogeneous and constrained environments of many synthetic and biological systems.

Surface binding of polymer coated nanoparticles: Coupling of physical interactions, molecular organization, and chemical state

246th National Meeting (2013)

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