Elter Johanna K, Sedlák František, Palušák Tomáš, Bernardová Nicol, Lobaz Volodymyr, Tihlaříková Eva, Neděla Vilém, Šácha Pavel, Hrubý Martin
Institute of Macromolecular Chemistry, CAS, Heyrovského nám. 2, Praha 6 162 06, Czech Republic.
Institute of Biochemistry and Experimental Oncology, First Faculty of Medicine, U Nemocnice 5, Praha 2 128 53, Czech Republic.
Biomacromolecules. 2025 Feb 10;26(2):861-882. doi: 10.1021/acs.biomac.4c01052. Epub 2025 Jan 8.
Multifunctional polymers are interesting substances for the formulation of drug molecules that cannot be administered in their pure form due to their pharmacokinetic profiles or side effects. Polymer-drug formulations can enhance pharmacological properties or create tissue specificity by encapsulating the drug into nanocontainers, or stabilizing nanoparticles for drug transport. We present the synthesis of multifunctional poly(2-ethyl-2-oxazoline--2-glyco-2-oxazoline)s containing two reactive end groups, and an additional hydrophobic anchor at one end of the molecule. These polymers were successfully used to stabilize (solid) lipid nanoparticles ((S)LNP) consisting of tetradecan-1-ol and cholesterol with their hydrophobic anchor. While the pure polymers interacted with GLUT1-expressing cell lines mainly based on their physicochemical properties, especially interactions of the hydrophobic anchor with membranous compartments of the cells, LNP-cell interactions hinted toward an influence of the glucosylation on particle-cell interactions. The presented LNP are therefore promising systems for the delivery of drugs into GLUT1-expressing cell lines.
多功能聚合物是用于药物分子制剂的有趣物质,这些药物分子由于其药代动力学特征或副作用而不能以纯形式给药。聚合物-药物制剂可以通过将药物封装到纳米容器中,或稳定用于药物运输的纳米颗粒来增强药理特性或产生组织特异性。我们展示了含有两个反应性端基且在分子一端带有额外疏水锚定基团的多功能聚(2-乙基-2-恶唑啉-2-糖基-2-恶唑啉)的合成。这些聚合物成功地用于通过其疏水锚定基团稳定由十四烷-1-醇和胆固醇组成的(固体)脂质纳米颗粒((S)LNP)。虽然纯聚合物主要基于其物理化学性质与表达GLUT1的细胞系相互作用,特别是疏水锚定基团与细胞膜区室的相互作用,但LNP与细胞的相互作用暗示糖基化对颗粒-细胞相互作用有影响。因此,所展示的LNP是将药物递送至表达GLUT1的细胞系的有前景的系统。