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Affinity-Based Functionalization of Biomedically Utilized Micelles Composed of Triblock Copolymers through Polymer-Binding Peptides
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2019-03-21 , DOI: 10.1021/acsbiomaterials.8b01513 Toshiki Sawada 1, 2 , Misaki Takizawa 1 , Takeshi Serizawa 1
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2019-03-21 , DOI: 10.1021/acsbiomaterials.8b01513 Toshiki Sawada 1, 2 , Misaki Takizawa 1 , Takeshi Serizawa 1
Affiliation
Polymeric micelles and vesicles that are self-assembled from amphiphilic block copolymers are frequently used in biomedical applications. Poly(ethylene oxide) (PEO)–poly(propylene oxide) (PPO)–PEO, so-called Pluronic, is a Food and Drug Administration approved triblock copolymer utilized in biomedical applications. However, the control of drug loading and surface functionalization of micelles remain challenging due to structural limitations. In this study, Pluronic micelles with various structures were rationally functionalized via the PPO-binding peptide, which was previously identified using a biologically constructed peptide library displayed on filamentous phages. The interactions between the peptide and Pluronic micelles were characterized in detail based on fluorescence changes in an extrinsic fluorescence dye, and a sufficient PPO chain length of Pluronic was essential for the interactions. Furthermore, enzymatic degradation of the model substrate-conjugated peptide loaded into Pluronic micelles showed stable loading of the peptide. Importantly, the exposure level of the conjugated molecules to the peptide was dependent on the PEO chain length of Pluronic, suggesting controllable functionalization of polymeric micelles. Anticancer drug-conjugated peptide-loaded Pluronic micelles with suitable polymeric structures were applied in a cell culture assay. The anticancer efficacy of the loaded drugs can be controlled by the molecular design of the binding peptide and polymers. These results demonstrate that an affinity-based functionalization strategy may facilitate polymeric micelles for various biomedical applications.
中文翻译:
基于亲和力的三嵌段共聚物通过聚合物结合肽组成的生物医学利用胶束的功能化。
由两亲性嵌段共聚物自组装的聚合物胶束和囊泡经常用于生物医学应用中。聚环氧乙烷(PEO)-聚环氧丙烷(PPO)-PEO,即所谓的Pluronic,是美国食品药品监督管理局(FDA)批准的用于生物医学领域的三嵌段共聚物。然而,由于结构限制,控制胶束的载药量和表面功能化仍然具有挑战性。在这项研究中,具有多种结构的Pluronic胶束通过PPO结合肽得到了合理的功能化,而PPO结合肽是先前使用展示在丝状噬菌体上的生物学构建的肽库进行鉴定的。根据外在荧光染料中的荧光变化,详细描述了肽与Pluronic胶束之间的相互作用 Pluronic的PPO链长对于相互作用至关重要。此外,加载到Pluronic胶束中的模型底物偶联肽的酶促降解显示出该肽的稳定加载。重要的是,共轭分子对肽的暴露水平取决于Pluronic的PEO链长,表明聚合物胶束的可控功能化。具有合适的聚合物结构的抗癌药物缀合的肽负载的Pluronic胶束用于细胞培养测定。负载药物的抗癌功效可以通过结合肽和聚合物的分子设计来控制。这些结果表明,基于亲和力的功能化策略可以促进聚合物胶束用于各种生物医学应用。
更新日期:2019-05-23
中文翻译:
基于亲和力的三嵌段共聚物通过聚合物结合肽组成的生物医学利用胶束的功能化。
由两亲性嵌段共聚物自组装的聚合物胶束和囊泡经常用于生物医学应用中。聚环氧乙烷(PEO)-聚环氧丙烷(PPO)-PEO,即所谓的Pluronic,是美国食品药品监督管理局(FDA)批准的用于生物医学领域的三嵌段共聚物。然而,由于结构限制,控制胶束的载药量和表面功能化仍然具有挑战性。在这项研究中,具有多种结构的Pluronic胶束通过PPO结合肽得到了合理的功能化,而PPO结合肽是先前使用展示在丝状噬菌体上的生物学构建的肽库进行鉴定的。根据外在荧光染料中的荧光变化,详细描述了肽与Pluronic胶束之间的相互作用 Pluronic的PPO链长对于相互作用至关重要。此外,加载到Pluronic胶束中的模型底物偶联肽的酶促降解显示出该肽的稳定加载。重要的是,共轭分子对肽的暴露水平取决于Pluronic的PEO链长,表明聚合物胶束的可控功能化。具有合适的聚合物结构的抗癌药物缀合的肽负载的Pluronic胶束用于细胞培养测定。负载药物的抗癌功效可以通过结合肽和聚合物的分子设计来控制。这些结果表明,基于亲和力的功能化策略可以促进聚合物胶束用于各种生物医学应用。