Bixenmann Leon, Ahmad Taufiq, Stephan Fabian, Nuhn Lutz
Institute of Functional Materials and Biofabrication, Department of Chemistry and Pharmacy, Julius-Maximilians-Universität Würzburg, 97070 Würzburg, Germany.
Max Planck Institute for Polymer Research, 55128 Mainz, Germany.
Biomacromolecules. 2024 Dec 9;25(12):7958-7974. doi: 10.1021/acs.biomac.4c01229. Epub 2024 Nov 7.
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' 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.
主链中含有半缩醛酯的聚合物为（免疫）药物递送提供了有益的降解特性。然而，它们的快速水解和低药物负载能力迄今为止限制了它们的应用。因此，本研究聚焦于半缩醛酯聚合物的稳定性和负载能力。胶束核心的疏水性对半缩醛酯稳定性有巨大影响。为此，我们引入一种带有苯基部分的新单体来稳定胶束核心并提高药物负载量。载体功能可通过聚合物链端的活化酯基团进行后聚合修饰进一步扩展。这使得能够进行共价染料标记，从而为聚合物的性能提供大量见解。对RAW双巨噬细胞的流式细胞术分析表明，完整的胶束与降解产物相比表现出显著更高的细胞摄取，因此，突出了端基功能化聚（半缩醛酯）用于（免疫）药物递送目的的潜力。
