Shi Yiqi, Yu Qianqian, Tan Lijie, Wang Qi, Zhu Wei-Hong
Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Shanghai Key Laboratory of Functional Materials Chemistry, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, 200237, P.R. China.
Department of Thoracic Surgery, Cancer Center, Zhongshan Hospital of Fudan University, Shanghai, P.R. China.
Angew Chem Int Ed Engl. 2025 Jun 24;64(26):e202503776. doi: 10.1002/anie.202503776. Epub 2025 Apr 25.
Most chemotherapeutic and bioimaging agents struggle with inadequate bioavailability, primarily due to their limited biocompatibility and lack of specificity in targeting, leading to low or decreased anticancer efficacy and inaccurate imaging. To surmount these obstacles, the development of stimuli-responsive polymer delivery platforms, predominantly leveraging the tumor microenvironment (TME), has emerged as a promising strategy. Therapeutic and diagnostic agents can be released controllably at the tumor site by virtue of the bond cleavage or hydrophobic to hydrophilic transformation of TME-sensitive linkages in TME-responsive systems, thus augmenting cancer treatment and imaging precision, while simultaneously attenuating the damage to healthy tissues and false imaging signals caused by non-specific drug leakage. In this comprehensive review, we scrutinize recent studies of TME-responsive polymer delivery platforms, encompassing pH-, ROS-, GSH-, enzyme-, and hypoxia-responsive vectors, significantly from the perspective of their molecular design and responsive mechanism, and further summarizing their bio-application in drug delivery and diagnostic imaging. Moreover, this review encapsulates the critical challenges and offers an insightful perspective on the future prospects of TME-responsive polymer delivery platforms in terms of molecular and vector design.
大多数化疗药物和生物成像剂都存在生物利用度不足的问题，主要原因是它们的生物相容性有限且靶向缺乏特异性，导致抗癌疗效低下或降低以及成像不准确。为了克服这些障碍，主要利用肿瘤微环境（TME）的刺激响应聚合物递送平台的开发已成为一种有前景的策略。在TME响应系统中，治疗剂和诊断剂可通过TME敏感键的键断裂或由疏水向亲水转变在肿瘤部位可控释放，从而提高癌症治疗和成像精度，同时减少非特异性药物泄漏对健康组织造成的损害和假成像信号。在这篇综述中，我们从分子设计和响应机制的角度详细审视了TME响应聚合物递送平台的最新研究，包括pH、ROS、GSH、酶和缺氧响应载体，并进一步总结了它们在药物递送和诊断成像中的生物应用。此外，本综述总结了关键挑战，并就TME响应聚合物递送平台在分子和载体设计方面的未来前景提供了有见地的观点。
