Post-Polymerization Modifications to Prepare Biomedical Nanocarriers with Varying Internal Structures, their Properties and Impact on Protein Corona Formation

The reactive ester approach provides access to various types of drug delivery systems. Either amphiphilic block copolymer micelles with hydrophobic cores can be generated for encapsulation of hydrophobic drugs, or they are (reversibly) crosslinked by polar molecules into nano(hydro)gel particles affording hydrophilic cores and coronas. Beyond short oligonucleotides complexation or covalent drug conjugation inside the core, a surface functionalization with targeting units is further possible to address a large variety of drug delivery scenarios. Interestingly, the reactive ester approach can thereby not only govern the nanocarriers' inner structure and surface property, but at the same time also provide strategies to prevent protein corona formation. These features are summarized in this article and underline the concept of reactive ester macromolecules as beneficial tool for assisting in drug delivery. Via controlled polymerization techniques various copolymer architectures can be generated with reactive ester domains. Depending on the drug delivery purpose, these domains are either converted into amphiphilic polymer micelles or reversibly crosslinked into hydrophilic nano(hydro)gels. Thereby, the interaction with plasma proteins can be controlled in order to prevent protein corona formation.image