Multivalent targeting of GLUT5-transporters through wormlike micelles with controlled size, stability, and ligand density

通过大小、稳定性和配体密度受控的蠕虫状胶束对 GLUT5 转运蛋白进行多价靶向

• 批准号: 317002573
• 负责人: Privatdozent Dr. Michael Gottschaldt
• 金额: --
• 依托单位: Institut für Organische Chemie und Makromolekulare Chemie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/317002573?language=en
• 关键词: Multivalent; targeting; GLUT5; transporters; through

The aim of this project is the preparation of wormlike micelles with controlled length, stability, and composition for selective uptake into breast cancer cells via multivalent targeting. This is realized through the synthesis of amphiphilic polyether- and polyester-based block copolymers with varying weight fractions and crosslinkable units in the side chain of the hydrophobic segment. Further, differently functionalized derivatives of 2,5-anhydromannitol (AMtl) will be synthesized and covalently attached to the hydrophilic block using suitable conjugation reactions. AMtl features a high affinity to a fructose-selective transporter, GLUT5, which is known to be overexpressed in many breast cancer cell lines. Subsequent co-assembly strategies using different block copolymer mixtures with varying content of AMtl-units allow then the preparation of wormlike micelles with controllable density of AMtl within the micellar corona. Depending on length and flexibility of such nanostructures, several GLUT5-receptors on the surface of such cells can now be addressed simultaneously. In that way, we aim at a higher specificity of wormlike micelles if compared to spherical analogues with regard to the targeted breast cancer cell lines. Within the framework of this project, we will also investigate the influence of micellar stability (e.g., mediated using core crosslinking) on cell uptake via endocytosis under static and dynamic conditions. As an alternative to core-crosslinking, we will also employ hydrolytically sensitive polyester blocks as core-forming segments.

该项目的目的是制备具有可控长度、稳定性和组成的蠕虫状胶束，用于通过多价靶向选择性摄取到乳腺癌细胞中。这是通过合成具有不同重量分数和疏水链段侧链中的可交联单元的两亲性聚醚和聚酯基嵌段共聚物来实现的。此外，将合成2，5_脱水甘露醇（AMtl）的不同官能化衍生物，并使用合适的缀合反应将其共价连接至亲水性嵌段。AMt 1具有对果糖选择性转运蛋白GLUT 5的高亲和力，已知GLUT 5在许多乳腺癌细胞系中过表达。随后的共组装策略，使用不同的嵌段共聚物混合物与不同含量的AMtl-单元，然后允许蠕虫状胶束的制备与可控密度的AMtl内的胶束冠。根据这种纳米结构的长度和灵活性，现在可以同时处理这种细胞表面上的几种GLUT 5受体。以这种方式，我们的目标是更高的特异性蠕虫状胶束相比，球形类似物方面的靶向乳腺癌细胞系。在这个项目的框架内，我们还将研究胶束稳定性的影响（例如，使用核心交联介导）对静态和动态条件下经由内吞作用的细胞摄取的影响。作为核交联的替代方案，我们还将采用水解敏感性聚酯嵌段作为核形成链段。

项目成果

Synthesis of a fructose decorated PAGE-b-PEG-b-PLGA polymer with subsequent formulation of nanoparticles

• DOI: 10.1016/j.colsurfa.2020.124701
• 发表时间: 2020-07
• 期刊: Colloids and Surfaces A: Physicochemical and Engineering Aspects
• 作者: J. Czaplewska;G. Gangapurwala;A. Vollrath;Michael Pröhl;Tobias C. Majdanski;D. Pretzel;S. Hoeppener;U. Schubert;M. Gottschaldt

Core-crosslinked diblock terpolymer micelles – taking a closer look on crosslinking efficiency

• DOI: 10.1039/c8py00126j
• 发表时间: 2018-05
• 期刊: Polymer Chemistry
• 影响因子: 4.6
• 作者: Johanna K. Elter;Gabriele Sentis;Peter Bellstedt;P. Biehl;M. Gottschaldt;F. Schacher

Core-crosslinked worm-like micelles from polyether-based diblock terpolymers

由聚醚基二嵌段三元共聚物制成的核交联蠕虫状胶束

• DOI: 10.1039/c9py01054h
• 发表时间: 2019
• 期刊: Polymer Chemistry
• 影响因子: 4.6
• 作者: J. K. Elter;P. Biehl;M. Gottschaldt;F. H. Schacher
• 通讯作者: F. H. Schacher

Synthesis of d-fructose conjugated ligands via C6 and C1 and their corresponding [Ru(bpy)2(L)]Cl2 complexes.

• DOI: 10.1016/j.carres.2017.04.020
• 发表时间: 2017-06
• 期刊: Carbohydrate research
• 影响因子: 3.1
• 作者: Michael Pröhl;Pascal Moser;J. Czaplewska;P. Hoffmann;Tanja Buś;Anja Traeger;H. Goerls;U. Schubert;M. Gottschaldt

Microfabrication of 3D-hydrogels via two-photon polymerization of poly(2-ethyl-2-oxazoline) diacrylates

• DOI: 10.1016/j.eurpolymj.2019.109295
• 发表时间: 2020-01
• 期刊: European Polymer Journal
• 影响因子: 6
• 作者: Thomas Wloka;Steffen Czich;Maximilian Kleinsteuber;Elisabeth Moek;Christine Weber;M. Gottschaldt;K. Liefeith;U. Schubert