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 a...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.展开更多
基金supported by the National Natural Science Foundation of China (51472252 and 51572269)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB17000000)
文摘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.
