具有天然小分子侧基和最高临界溶液温度的嵌段聚合物的合成与载药性质研究

Polymers possessing an upper critical solution temperature (UCST) are the attractive candidates for biomaterials. For example, drugs may be entrapped in UCST polymers below 37 °C and then become released above body temperature. A tissue sample could be initially cultured on a coating made of a UCST polymer at a lower temperature and then the ready detachment of the grown tissue at a slightly higher temperature. To date, the library of UCST polymers in water is limited. Comonomers such as styrene and acrylonitrile in these UCST copolymers may be unsafe as biomaterials. Moreover, they cannot deliver the drugs to the targeted area. In this program, a bile acid-based monomer is chosen as a hydrophobic comonomer and copolymerized with acrylamide via reversible addition and fragmentation chain transfer (RAFT) polymerization. The resulting copolymers are expected to exhibit UCST responsiveness in water by varying the monomer ratio. Glucose molecules are also incorporated into the polymers as the second block to introduce the receptor of some proteins. The combination of natural compound and amide-containing monomer to prepare UCST responsive polymers not only enlarges the repertoire of UCST copolymers in water, but also improves the biocompatibility of the resulting materials. These block copolymers will be tested as drug delivery system to study the ability to convey drugs to the targeted area and release drug molecules within key cells in a controlled manner.

具有最高临界溶液温度（UCST）的聚合物在生物医药领域具有非常诱人的应用前景。例如，可以作为药物载体实现药物的可控释放，以及在聚合物基质上培养可以自动脱落的组织。然而目前，具有UCST的聚合物的种类还较少，且作为聚合物药物载体，其生物相容性差、缺少载药的靶向性。本项目拟通过选择天然分子胆酸的衍生物作为疏水单体和丙烯酰胺在活性聚合的条件下共聚，通过调节单体的比例来获得具有UCST的聚合物。通过引入天然糖分子的嵌段，实现聚合物对于蛋白和细胞的靶向识别。天然疏水分子与酰胺类单体组合的策略，不但为合成新的具有UCST的聚合物提供了简单的方法，同时还意在提高所得聚合物的生物相容性。尝试将所得嵌段聚合物作为药物载体，探索其对负载药物的可控释放和靶向给药。

具有最高临界溶液温度（UCST）的聚合物在生物医药领域具有非常诱人的应用前景。例如，可以作为药物载体实现药物的可控释放，以及在聚合物基质上培养可以自动脱落的组织。然而目前，具有UCST的聚合物的种类还较少，且作为聚合物药物载体，其生物相容性差、缺少载药的靶向性。本项目通过选择天然分子胆酸的衍生物作为疏水单体和丙烯酰胺在活性聚合的条件下共聚，通过调节单体的比例来获得具有UCST的聚合物。通过引入天然糖分子的嵌段，实现聚合物对于特异微生物的靶向识别。同时为了赋予聚合物载体可视化功能，将具有聚集诱导发光（AIE）性质的四苯基乙烯片段作为疏水分子引入到UCST体系中。目前在以下三部分取得重要进展：.1）成功以天然无毒的胆酸分子和糖分子为原料，结合具有稳定AIE性质的四苯基乙烯分子，设计和合成一系列生物相容性良好且具有AIE和UCST响应的嵌段聚合物，实现了UCST的可调控性；.2）所得UCST聚合物作为药物载体实现负载药物的温度刺激下的精准可控释放，并成功利用聚合物的AIE性质实现对UCST相变过程和药物释放过程的监控；.3）利用含糖嵌段聚合物对大肠杆菌壁膜结构上特异蛋白的靶向性，实现了在温度刺激下聚合物对大肠杆菌聚集行为的可视化调控，即AIE成像下的温度可逆聚集行为的调控。.前一部分核心工作已经以Visualizing phase transition of upper critical solution temperature (UCST) polymers with AIE为题在Sci. China Chem.上发表，含糖嵌段聚合物和细菌细胞靶向部分也已完成，目前已经进入文章撰写和投稿阶段（AIE-Active UCST Polyvalent Scaffolds Visualizing the Sweet Talking of Bacteria）。

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