Affinity-Based Functionalization of Biomedically Utilized Micelles Composed of Triblock Copolymers through...

Polymeric micelles and vesicles that are self-assembled from amphiphilic block copolymers are frequently used in biomedical applications. Poly(ethylene oxide) (PEO)-poly(propylene oxide) (PPO)-PEO, so-called Pluronic, is a Food and Drug Administration approved triblock copolymer utilized in biomedical applications. However, the control of drug loading and surface functionalization of micelles remain challenging due to structural limitations. In this study, Pluronic micelles with various structures were rationally functionalized via the PPO-binding peptide, which was previously identified using a biologically constructed peptide library displayed on filamentous phages. The interactions between the peptide and Pluronic micelles were characterized in detail based on fluorescence changes in an extrinsic fluorescence dye, and a sufficient PPO chain length of Pluronic was essential for the interactions. Furthermore, enzymatic degradation of the model substrate-conjugated peptide loaded into Pluronic micelles showed stable loading of the peptide. Importantly, the exposure level of the conjugated molecules to the peptide was dependent on the PEO chain length of Pluronic, suggesting controllable functionalization of polymeric micelles. Anticancer drug-conjugated peptide-loaded Pluronic micelles with suitable polymeric structures were applied in a cell culture assay. The anticancer efficacy of the loaded drugs can be controlled by the molecular design of the binding peptide and polymers. These results demonstrate that an affinity-based functionalization strategy may facilitate polymeric micelles for various biomedical applications.