End-Group Dye-Labeled Poly(hemiacetal ester) Block Copolymers: Enhancing Hydrolytic Stability and Loading Capacity for Micellar (Immuno-)Drug Delivery

Polymers with hemiacetal esters integrated in their backbone provide beneficial degradation profiles for (immuno-) drug delivery. However, their fast hydrolysis and low drug loading capacity have limited their applications so far. Therefore, this study focuses on the stability and loading capacity of hemiacetal ester polymers. The hydrophobicity of the micellar core has a tremendous effect on the hemiacetal ester stability. For that purpose, we introduce a new monomer with a phenyl moiety for stabilizing the micellar core and improving drug loading. The carrier functionality can further be expanded by post-polymerization modifications via activated ester groups at the polymer chain end. This allows for covalent dye labeling, which provides substantial insights into the polymers’ in vitro performance. Flow cytometric analyses on RAW dual macrophages revealed intact micelles exhibiting significantly higher cellular uptake compared to degraded species, thus, highlighting the potential of end group functionalized poly­(hemiacetal ester)­s for (immuno)­drug delivery purposes.