High-Performance Chromatographic Characterization of Surface Chemical Heterogeneities of Fluorescent Organic–Inorganic Hybrid Core–Shell Silica Nanoparticles

Abstract

In contrast to small molar mass compounds, detailed structural investigations of inorganic coreorganic ligand shell hybrid nanoparticles remain challenging. Assessment of batch reaction induced heterogeneities of surface chemical properties and their correlation with particle size has been a particularly long-standing issue. Applying a combination of high performance liquid chromatography (HPLC) and gel permeation chromatography (GPC) to ultrasmall (< 10 nm diameter) poly(ethylene glycol) coated (PEGylated) fluorescent core-shell silica nanoparticles, here we elucidate previously unknown surface heterogeneities resulting from varying dye conjugation to nanoparticle silica cores and surfaces. Heterogeneities are predominantly governed by dye charge as corroborated by molecular dynamics simulations. We demonstrate that this insight enables development of synthesis protocols to achieve PEGylated and targeting ligand functionalized PEGylated silica nanoparticles with dramatically improved surface chemical homogeneity as evidenced by single peak HPLC chromatograms. Since surface chemical properties are key to all nanoparticle interactions, we expect these methods and fundamental insights to become relevant to a number of systems for applications including bioimaging and nanomedicine.

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