End-Group Dye-Labeled\nPoly(hemiacetal ester) Block\nCopolymers: Enhancing Hydrolytic Stability and Loading Capacity for\nMicellar (Immuno-)Drug Delivery

Polymers with hemiacetal esters integrated in their backbone\nprovide\nbeneficial degradation profiles for (immuno-) drug delivery. However,\ntheir fast hydrolysis and low drug loading capacity have limited their\napplications so far. Therefore, this study focuses on the stability\nand loading capacity of hemiacetal ester polymers. The hydrophobicity\nof the micellar core has a tremendous effect on the hemiacetal ester\nstability. For that purpose, we introduce a new monomer with a phenyl\nmoiety for stabilizing the micellar core and improving drug loading.\nThe carrier functionality can further be expanded by post-polymerization\nmodifications via activated ester groups at the polymer chain end.\nThis allows for covalent dye labeling, which provides substantial\ninsights into the polymers’ <i>in vitro</i> performance.\nFlow cytometric analyses on RAW dual macrophages revealed intact micelles\nexhibiting significantly higher cellular uptake compared to degraded\nspecies, thus, highlighting the potential of end group functionalized\npoly(hemiacetal ester)s for (immuno)drug delivery purposes.