γ-Glutamyl transpeptidase-activatable near-infrared nanoassembly for tumor fluorescence imaging-guided photothermal therapy

γ-谷氨酰转肽酶激活的近红外纳米组装体用于肿瘤荧光成像引导的光热治疗

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作者:Fangyuan Zhou, Shikui Yang, Chao Zhao, Wangwang Liu, Xufeng Yao, Hui Yu, Xiaolian Sun, Yi Liu

Conclusions

NRh-G-NPs were specifically responsive to GGT overexpressed in U87MG tumor cells and selectively lit up the tumor for imaging-guided therapy. Besides, the recovery of photothermal property in the tumor area could improve cancer therapy precision and decreased side effects in normal tissues.

Methods

The GGT responsive NIR probe was constructed by conjugating GGT-specific substrate γ-glutamic acid (γ-Glu) with cyanine fluorophore (NRh-NH2) via amide reaction. The resulting NRh-G spontaneously assembled into nanoparticles (NRh-G-NPs) around 50 nm. The NPs were characterized and the properties evaluated in the presence or absence of GGT. Subsequently, we studied fluorescence imaging and photothermal therapy of NRh-G-NPs in vitro and in vivo.

Results

NRh-G-NPs, upon specific reaction with GGT, turned into NRh-NH2-NPs, showing a ~180-fold fluorescence enhancement and excellent photothermal effect recovery. NRh-G-NPs could selectively light up U87MG tumor cells while their fluorescence was weak in L02 human normal liver cells. The NPs also showed excellent tumor cell ablation upon laser irradiation. After intravenous injection into tumor-bearing mice, NRh-G-NPs could arrive in the tumor area and specifically light up the tumor. Following laser irradiation, the tumor could be completely erased with no tumor reoccurrence for up to 40 days. Conclusions: NRh-G-NPs were specifically responsive to GGT overexpressed in U87MG tumor cells and selectively lit up the tumor for imaging-guided therapy. Besides, the recovery of photothermal property in the tumor area could improve cancer therapy precision and decreased side effects in normal tissues.

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