Quantitatively Tracking Bio–Nano Interactions of Metal–Phenolic Nanocapsules by Mass Cytometry

Polymer nanocapsules, with a hollow structure, are increasingly finding widespread use as drug delivery carriers; however, quantitatively evaluating the bio–nano interactions of nanocapsules remains challenging. Herein, poly­(ethylene glycol) (PEG)-based metal–phenolic network (MPN) nanocapsules of three sizes (50, 100, and 150 nm) are engineered via supramolecular template-assisted assembly and the effect of the nanocapsule size on bio–nano interactions is investigated using in vitro cell experiments, ex vivo whole blood assays, and in vivo rat models. To track the nanocapsules by mass cytometry, a preformed gold nanoparticle (14 nm) is encapsulated into each PEG–MPN nanocapsule. The results reveal that decreasing the size of the PEG–MPN nanocapsules from 150 to 50 nm leads to reduced association (up to 70%) with phagocytic blood cells in human blood and prolongs in vivo systemic exposure in rat models. The findings provide insights into MPN-based nanocapsules and represent a platform for studying bio–nano interactions.