Abstract：
A cancer-targeted glutathione (GSH)-gated theranostic probe (CGT probe) for intracellular miRNA imaging and combined treatment of self-sufficient starvation therapy (ST) and chemodynamic therapy (CDT) was developed. The CGT probe is constructed using MnO2 nanosheet (MS) as carrier material to adsorb the elaborately designed functional DNAs. It can be internalized by cancer cells via specific recognition between the AS1411 aptamer and nucleolin. After CGT probe entering the cancer cells, the overexpressed GSH, as gate-control, can degrade MS to Mn2+ which can be used for CDT by Fenton-like reaction. Simultaneously, Mn2+-mediated CDT can further cascade with the enzyme-like activities (catalase-like activity and glucose oxidase-like activity) of CGT probe, achieving self-sufficient ST/CDT synergistic therapy. Meanwhile, the anchored DNAs are released, achieving in situ signal amplification via disubstituted-catalytic hairpin assembly (DCHA) and FRET (fluorescence resonance energy transfer) imaging of miR-21. The in vitro and in vivo experiments demonstrated that accurate and sensitive miRNA detection can be achieved using the CGT probe. Overall, the ingenious CGT probe opens a new avenue for the development of early clinical diagnosis and cancer therapy.
摘要：
开发了一种用于细胞内miRNA成像和自给自足饥饿疗法（ST）和化学动力学疗法（CDT）的联合治疗的癌症靶向谷胱甘肽（GSH）门控治疗探针（CGT探针）。CGT探针是使用MnO2纳米片（MS）作为载体材料构建的，以吸附精心设计的功能DNA。它可以通过AS1411适体和核仁素之间的特异性识别被癌细胞内化。CGT探针进入癌细胞后，过度表达的GSH，作为栅极控制，可以通过类Fenton反应将MS降解为可用于CDT的Mn2。同时,Mn2+介导的CDT可以进一步与CGT探针的酶样活性（过氧化氢酶样活性和葡萄糖氧化酶样活性）级联，实现自给自足的ST/CDT协同治疗。同时,锚定的DNA被释放，通过miR-21的双取代催化发夹组装（DCHA）和FRET（荧光共振能量转移）成像实现原位信号放大。体外和体内实验表明，使用CGT探针可以实现准确和灵敏的miRNA检测。总的来说,巧妙的CGT探针为早期临床诊断和癌症治疗的发展开辟了新途径。
