Polymersome-Encapsulated Chemosensors: New Design Strategies toward Biofluid-Applicable Cucurbit[7]uril Indicator Displacement Assays

The development of supramolecular cucurbit[7]uril-based chemosensors for the detection of bioanalytes in biofluids such as untreated human serum and inside cells is a challenging task due to competition with proteins and inorganic salts. In this contribution, we show that the encapsulation of cucurbit[7]uril-based chemosensors in polymersomes can prevent deactivation, rendering the chemosensors operational in human serum and inside cells. We found that polymersomes with a hydrophilic poly-[N,N-dimethylacrylamide] corona, especially those smaller than 200 nm, exhibit greater permeability to small bioactive molecules compared with polymersomes with a bulkier poly(ethylene glycol) corona. Furthermore, analytes characterized by intermediate lipophilicity, low charge density, and a rigid structure display enhanced permeability through the polymersomes. The polymer membrane serves as a selective filter that allows small molecules to pass through a chemosensor while larger proteins are held outside the polymersome. In addition to providing a new approach for stabilizing chemosensors in protein-rich media, this study underscores the potential utility of polymersome-encapsulated chemosensors in investigating membrane permeability.