针对传统的药物输运聚合物胶束纳米载体存在的结构稳定性差、释放不可控、不能协同/联合给药以及功能较单一等局限性，本项目拟围绕基于多臂星型二嵌段共聚物的结构稳定单分子胶束设计合成具有肿瘤微环境响应原药释放特性的药物共输运高分子前药体系以及兼具响应性调控磁共振信号强度和原药释放复合功能的新型诊疗体系。在设计合成四类分别对酶、过氧化氢、pH值和巯基响应性触发释放原药的可聚合或反应性前药基元的基础上，将其共价结合到单分子胶束纳米载体上，以实现两种抗肿瘤药物的共输运和响应性释放，达到联合/协同治疗的目的；还将融合生物环境响应性调控磁共振成像造影功能的新概念，并结合肿瘤靶向输运和给药以及响应性原药释放等策略，设计合成具有复合功能的"可视化"治疗体系。该项目的实施预期将有助于提高药物的生物利用率并有效降低抗肿瘤药物对正常细胞与组织的毒副作用，为新一代功能性纳米载体体系的设计提供重要参考。

Aiming to solve major limitations encountered with conventional polymeric micelles-based drug delivery nanocarriers such as low structural stability, uncontrolled release, unsuitable for cooperative/ combined drug administration, and only possessing a single function, in this funding proposal we attempt to design co-delivery polymeric prodrugs possessing biologically-responsive release characteristics and dually functional polymeric prodrugs capable of external stimuli-tunable magnetic resonance imaging (MRI) contrast effects and biologically-responsive triggered-release of potent drugs with intact chemical structures by utilizing structurally stable unimolecular micelles of multi-arm star diblock copolymers as the platform. We plan to design and synthesize four types of structurally novel and polymerizable or reactive prodrug building blocks which are biologically responsive to a specific enzyme, hydrogen peroxide, mildly acidic pH, or thiol compounds and capable of releasing potent drugs, and covalently conjugate them onto unimolecular micelles-based nanocarriers, thus, the co-delivery and responsive co-release of two types of chemotherapeutic drugs will be achieved for the purpose of combined and cooperative chemotherapy. We will also integrate the new concept of modulating MRI contrast effects via external stimuli with strategies of tumor-targeted drug delivery and stimuli-triggered anti-tumor drug release to design novel "image-guided" chemotherapy systems with combined functions. The accomplishment of the above proposed research contents is expected to significantly enhance the bioavailability of anti-tumor drugs and effectively reduce their undesirable side effects to normal cells and tissues, as well as provide an important reference for the construction of new generation functional nanocarrier systems.