聚乙二醇靶向纳米载体的制备及其药物传输的应用研究

When designing intelligent drug nanocarriers, it is essential to decrease non-specific biological interactions, increase circulation time, and improve tumor targeting ability. Surface functionalization of poly(ethylene glycol) (PEG) and conjugating targeting molecules on carriers are commonly used methods to increase circulation time and targeting ability, respectively. However, circulation time is dependent on PEG density and chain architecture, and it is challenging to achieve both non-specific biological interaction and specific targeting to tumors in one carrier. Herein, we engineer targeted PEG nanocarriers functionalized with targeting molecules via mesoporous silica templating and investigate the influence of the type and density of targeting molecules on biological interactions for targeted delivery of hydrophobic anti-cancer drugs. The designed nanocarriers, which are fully composed of PEG, could circumvent the issues of PEGylation relating to PEG density and configuration, thus prolonging circulation time. The PEG carriers are designed to be stealthy to normal cells but specifically targeted to cancer cells, improving drug delivery efficacy.

降低药物载体与生物体的非特异性相互作用，延长载体的循环时间以及提高载体对肿瘤的靶向功能是构筑智能纳米药物载体的关键。在载体表面修饰聚乙二醇和靶向分子是目前延长载体循环时间和提高靶向功能最常用的方法。然而，循环时间受到聚乙二醇密度和构型的制约，并且很难将载体与生物体的非特异性相互作用和载体的靶向性有效的结合在一起。本项目针对这两个难点，利用介孔二氧化硅模板法，设计并制备由聚乙二醇构成，表面修饰靶向分子的靶向纳米载体，研究靶向分子的种类和密度对载体与生物体相互作用的影响，探索该类载体在疏水药物靶向传输中的应用。本方案避免了载体表面修饰聚乙二醇存在的弊端，能更大程度延长载体的循环时间；目标构筑低免疫排外性和高靶向性于一体的聚合物载体，提高抗癌药物的给药效率。

本项目基于聚乙二醇（PEG）纳米载体能够显著降低与蛋白和细胞的相互作用这一优势，在其表面修饰靶向分子，内部封装治疗剂，构筑具有靶向功能的PEG纳米载体，并探索该类载体在药物传输中的应用。利用模板法组装PEG纳米载体并修饰不同的靶向分子，考察靶向分子的种类和修饰密度对载体生物行为的影响，获取靶向PEG载体的隐形性及靶向性之间的平衡关系；根据正常组织与肿瘤部位微环境的变化，设计并制备具有肿瘤微环境响应的PEG复合纳米载体，探究该载体与细胞的相互作用以及提高治疗剂功效的应用；采用超声聚合的方法一步构筑具有靶向性的PEG纳米载体，研究药物分子的封装以及可控释放，探索该载体在靶向药物运输中的应用。本研究旨在构筑靶向PEG纳米载体，增强载体的靶向功能，为降低药物的副作用并提高药物的给药效率提供新的方法和思路。