Targeted nanoparticles often require conjugating targeting ligands to polyethylene glycol (PEG) chains of a nanoparticle’s dense protecting corona. “Click” chemistries are commonly employed for their bioorthogonality, with strain-promoted azide–alkyne cycloadditions (SPAAC) increasingly chosen to avoid cytotoxic copper catalysts. However, conjugation becomes compromised if reactive PEG chain ends cannot encounter their reaction counterparts. We use fluorescence to probe the location of Nile Red, methylpyrene, and butylpyrene, dyes with comparable hydrophobicities to SPAAC alkynes (logP = 3.2–5.7), tethered to PEG chains on 100 nm NPs. Using fluorescence peak shifts, we find that Nile Red resides 43% of the time in the 5k PEG corona and 57% at the more hydrophobic nanoparticle core. Increasing the PEG MW to 67k doubles the corona dye fraction to 86% (14% core). More hydrophobic methylpyrene and butylpyrene, monitored with I1/I3 ratios, reside 1% in the corona (99% core). These results explain difficulties with using SPAAC reactions for conjugating large ligands to nanoparticles with PEG coronae.

We report approaches to the design of covalently crosslinked and physically stable surface coatings with chemically labile and dynamic surface features based on the functionalization of azlactone-containing materials with alcohol-, thiol-, and hydrazine-based nucleophiles. Past studies demonstrate that residual azlactone groups in polymer multilayers fabricated by the reactive layer-by-layer assembly of poly(2-vinyl-4,4-dimethylazlactone) and branched poly(ethylenimine) can react with amine-based nucleophiles to impart new surface and bulk properties through the creation of chemically stable amide/amide-type bonds. Here, we demonstrate that the azlactone groups in these covalently crosslinked materials can also be functionalized using less nucleophilic alcohol- or thiol-containing compounds, using an organic catalyst, or converted to reactive acylhydrazine groups by direct treatment with hydrazine. These methods (i) broaden the pool of molecules that can be used for post-fabrication functionalization to include compounds containing alcohol, thiol, or aldehyde groups and (ii) yield surface coatings with chemically labile amide/ester-, amide/thioester-, and amide/imine-type bonds that make possible the design of new dynamic and stimulus-responsive materials (e.g., surfaces that release covalently bound molecules or undergo changes in extreme wetting behaviors in response to specific chemical stimuli). Our results expand the range of functionality that can be installed in, and thus the range of new functions that can be imparted to, azlactone-containing coatings beyond those that can be accessed using primary amine-based nucleophiles. The chemical approaches demonstrated here using model polymer-based reactive multilayer coatings are general and should thus also prove useful for the design of new responsive surfaces based on other types of azlactone-functionalized materials.