Sawada Toshiki, Takizawa Misaki, Serizawa Takeshi
Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1-H121 Ookayama, Meguro-ku, Tokyo 152-8550, Japan.
Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi-shi, Saitama 332-0012, Japan.
ACS Biomater Sci Eng. 2019 Nov 11;5(11):5714-5720. doi: 10.1021/acsbiomaterials.8b01513. Epub 2019 Mar 21.
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.
由两亲性嵌段共聚物自组装而成的聚合物胶束和囊泡常用于生物医学应用。聚环氧乙烷（PEO）-聚环氧丙烷（PPO）-PEO，即所谓的普朗尼克，是一种经美国食品药品监督管理局批准的三嵌段共聚物，用于生物医学应用。然而，由于结构限制，胶束的药物负载控制和表面功能化仍然具有挑战性。在本研究中，通过PPO结合肽对具有各种结构的普朗尼克胶束进行了合理的功能化，该肽先前是使用展示在丝状噬菌体上的生物构建肽库鉴定出来的。基于外在荧光染料的荧光变化详细表征了肽与普朗尼克胶束之间的相互作用，并且普朗尼克足够的PPO链长对于这些相互作用至关重要。此外，对负载于普朗尼克胶束中的模型底物共轭肽的酶促降解显示肽的负载稳定。重要的是，共轭分子与肽的暴露水平取决于普朗尼克的PEO链长，这表明聚合物胶束的功能化是可控的。具有合适聚合物结构的负载抗癌药物共轭肽的普朗尼克胶束被应用于细胞培养试验。负载药物的抗癌功效可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能有助于聚合物胶束在各种生物医学应用中的应用。
