Komforth Patric, Imschweiler Jan, Hesse Milena, Heck Alina G, Fuchs Alexander, Hauck Adrian V, Nuhn Lutz
Chair of Macromolecular Chemistry, Julius-Maximilians-Universität Würzburg, Röntgenring 11, 97070 Würzburg, Germany.
Max Planck Institute for Polymer Research, Ackermannweg 10, 55128 Mainz, Germany.
Biomacromolecules. 2025 Jan 13;26(1):387-404. doi: 10.1021/acs.biomac.4c01207. Epub 2024 Dec 4.
Postpolymerization modifications are valuable techniques for creating functional polymers that are challenging to synthesize directly. This study presents aliphatic polycarbonates with pendant thiol-reactive groups for disulfide formation with mercaptans. The reductive responsive nature of this reaction allows for reversible postpolymerization modifications on biodegradable scaffolds. Six-membered cyclic carbonate monomers with pendant thiosulfonate groups were synthesized and polymerized using controlled organocatalytic ring-opening polymerization, yielding polymers with narrow molecular weight dispersities ( = 1.2) and intact reactive thiosulfonate side chains. Reversible modification with benzyl mercaptans achieved high degrees of disulfide modification. Additionally, thiol-reactive carbonate monomers were block-copolymerized onto polyethylene glycol (mPEG) and then converted into benzyl disulfides, while the block copolymers' hydroxyl end groups remained available for fluorescent dye labeling. The amphiphilic block copolymers self-assembled in water into micelles (∼33 nm diameter), capable of encapsulating hydrophobic molecules. These micelles successfully delivered hydrophobic dyes into macrophages, indicating the potential for intracellular drug delivery.
聚合后修饰是制备直接合成具有挑战性的功能聚合物的重要技术。本研究展示了带有侧链硫醇反应性基团的脂肪族聚碳酸酯，可与硫醇形成二硫键。该反应的还原响应特性使得在可生物降解支架上进行可逆的聚合后修饰成为可能。合成了带有侧链硫代磺酸酯基团的六元环状碳酸酯单体，并通过可控有机催化开环聚合进行聚合，得到分子量分散度窄（Đ = 1.2）且反应性硫代磺酸酯侧链完整的聚合物。用苄硫醇进行可逆修饰实现了高度的二硫键修饰。此外，硫醇反应性碳酸酯单体被嵌段共聚到聚乙二醇（mPEG）上，然后转化为苄基二硫化物，而嵌段共聚物的羟基端基仍可用于荧光染料标记。两亲性嵌段共聚物在水中自组装成胶束（直径约33 nm），能够包封疏水分子。这些胶束成功地将疏水性染料递送至巨噬细胞，表明其具有细胞内药物递送的潜力。
