Green Kevin A, Kulkarni Anuja S, Jankoski Penelope E, Worden Rachel M, Loving Bayleigh M, Derbigny Blaine, Clemons Tristan D, Watkins Davita L, Morgan Sarah E
School of Polymer Science and Engineering, The University of Southern Mississippi, Hattiesburg, Mississippi 39406, United States.
Department of Chemistry & Biochemistry, The Ohio State University, Columbus, Ohio 43210, United States.
Bioconjug Chem. 2025 Aug 20;36(8):1733-1743. doi: 10.1021/acs.bioconjchem.5c00217. Epub 2025 Jul 17.
Stereospecific arrangements of saccharide molecules control biological recognition and binding with proteins. These properties can also be utilized in the design of biomaterials for applications such as polymeric drug delivery, where saccharides may enhance the ability to target specific cells. Glycopolymer block copolymers incorporating pendant saccharides at high concentration have potential for use in applications; however, there is a need for further evaluation of their structure-property relationships. Accordingly, noncytotoxic amphiphilic, hybrid block copolymers (HBCs), synthesized by coupling branched polylactic acid (PLA) with linear polyacrylamides containing hydroxyethyl, β-d-glucose, or β-d-galactose moieties, were studied to determine the influence of the stereochemistry and structure of the pendant saccharide on nanoparticle formation, cargo loading, and lectin binding properties. HBCs were prepared at a target 50:50 PLA/hydrophilic block content; all compositions yielded similar spherical nanoparticle morphologies with comparable diameters on nanoprecipitation. Thermal properties and hydrophilic dye loading levels, however, were dependent on the pendant saccharide structure, attributed to differences in intramolecular interactions in the glycopolymer blocks. These findings demonstrate the importance of understanding the structure-dependent behavior for designing HBC-based therapies.
糖类分子的立体特异性排列控制着与蛋白质的生物识别和结合。这些特性也可用于生物材料的设计,如聚合物药物递送等应用,其中糖类可增强靶向特定细胞的能力。含有高浓度侧链糖类的糖聚合物嵌段共聚物具有潜在的应用价值;然而,需要进一步评估它们的结构-性能关系。因此,通过将支化聚乳酸(PLA)与含有羟乙基、β-D-葡萄糖或β-D-半乳糖部分的线性聚丙烯酰胺偶联合成了无细胞毒性的两亲性杂化嵌段共聚物(HBCs),以确定侧链糖类的立体化学和结构对纳米颗粒形成、载药量和凝集素结合特性的影响。在目标PLA/亲水嵌段含量为50:50的条件下制备了HBCs;所有组合物在纳米沉淀时都产生了类似的球形纳米颗粒形态,直径相当。然而,热性能和亲水染料负载水平取决于侧链糖类结构,这归因于糖聚合物嵌段中分子内相互作用的差异。这些发现证明了理解结构依赖性行为对于设计基于HBC的疗法的重要性。