LAUSR

The effect of tumor-targeted photodynamic therapy (PDT) was improved by designing nanotheranostics to promote oxygenation in a tumor microenvironment (TME) wherein hypoxia, acidosis, and the elevated levels of H2O2 are three main characteristics. In this study, a carbon dot (CD) PDT agent recently developed by our group was firstly applied as reducing agent to react with potassium permanganate for fabricating CDs/manganese dioxide (CDs/MnO2) composites, which were in turn modified with polyethylene glycol (PEG) to form water-soluble CDs/MnO2-PEG nanohybrids. In a normal physiological environment, the as-prepared nanohybrids exhibited quenched fluorescence, weak singlet oxygen generation, and low magnetic resonance imaging (MRI) signal. However, given the high sensitivity of MnO2 to the TME, the CDs/MnO2-PEG nanohybrids changed from an “off” to an “on” state with synchronously enhanced fluorescence, singlet oxygen generation, and MRI signal in the TME. In vitro and in vivo analyses have revealed that CDs/MnO2-PEG nanohybrids could be applied as TME-driven, turn-on nanotheranostics for the MR/fluorescence bimodal imaging-guided PDT of cancer. Moreover, complete clearance of CDs/MnO2-PEG nanohybrids from the body of mice was observed, indicating their low long-term toxicity and good biocompatibility. This work offers a new nanotheranostic candidate for modulating the unfavorable TME, particularly for the targeted PDT of cancer through precise positioning and oxygen generation.摘要缺氧、 过酸和过量的活性氧(如过氧化氢)是肿瘤微环境的三个主要显著特征, 针对这些特征可设计酸/过氧化氢响应的诊疗剂用于增强肿瘤靶向光动力治疗效果. 本文首次利用新型碳点光敏剂还原高锰酸钾制备碳点/二氧化锰, 然后利用聚乙二醇修饰形成水溶性的多功能复合物. 在正常生理环境中, 该聚乙二醇化的碳点光敏剂/二氧化锰纳米复合物的荧光大部分被淬灭, 光生单线态氧的能力被抑制, 也不具备磁共振成像的能力. 但是在肿瘤微环境中, 由于二氧化锰对酸/过氧化氢的高灵敏响应, 碳点荧光恢复, 同时可产生单线态氧, 能够检测到强的磁共振成像信号. 因此, 该水溶性聚乙二醇化的碳点/二氧化锰复合物可用于肿瘤微环境响应的荧光/磁共振双模态成像介导的 光动力治疗, 拓展了正电碳点作为新型光诊疗试剂在调节肿瘤微环境和增强光动力治疗方面的应用.