In contrast to small molar mass compounds, detailed structural investigations of inorganic core-polymer 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. Here we apply a combination of high performance liquid chromatography (HPLC) and gel permeation chromatography (GPC) to ultrasmall (&lt; 10 nm diameter) poly(ethylene glycol) coated (PEGylated) fluorescent core-shell silica nanoparticles (Cornell dots or C dots). C dots are the first investigational new drug (IND) FDA approved nanoparticles of their kind for human clinical trials. 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, which in turn improves biological response. This is exemplified by ferroptotic cell death experiments. 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 in nanomedicine and drug delivery.

High performance chromatographic characterization of surface chemical heterogeneities of fluorescent polymer-inorganic hybrid core-shell silica nanoparticles for drug delivery

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.