Distinctively different metabolism between tumor cells and normal cells endows tumor tissues unique microenvironment. In this regard, we have successfully prepared a sequential catalytic platform based on Au/Pt star for tumor theragnostic. The multifunctional probes consisted of a gold/platinum star-shaped core (Au/Pt star) conjugated with a GSH-sensitive disulfide bond (S-S), a targeting ligand (rHSA-FA), a near-infrared fluorophore (IR780) and glucose oxidase (GOx). When systemically administered in a xenografted murine model, the probes specifically targeted the tumor sites. As the disulfide linker was cleaved by intracellular GSH, the IR780 molecules could be released for photo-thermal therapy & photodynamic therapy (PTT&PDT) and imaging. Subsequently, the Pt nanolayer of the Au/Pt star and the GOx formed a sequential catalytic system: GOx effectively catalyzed intracellular glucose by consuming oxygen to generate H2O2 and enhance the local acidity, and the Pt layer exhibited peroxidase-like property to catalyze H2O2 producing toxic ·OH for tumor oxidative damage. Here we demonstrated that our probes simultaneously possessed a GSH-sensitive release, real-time imaging ability, and synergetic cancer starving-like therapy/enzyme oxidative therapy/PTT/PDT features, which provides a potential strategy for effective tumor theragnostic.
We thank the support of the National Basic Research Program of China (Nos. 2017YFA0205301 and 2015CB931802), the National Natural Scientific Foundation of China (Nos. 81903169, 81803094, 81602184, 81822024, and 81571729), Shanghai Municipal Commission of Economy and Information Technology Fund (No. XC-ZXSJ-02-2016-05), the Medical Engineering Cross Project of Shanghai Jiao Tong university (Nos. YG2016ZD10 and YG2017Z D05), the Project of Thousand Youth Talents from China, and the National Key Research and Development Program of China (No. 2017YFC1200904). We also are grateful for the financial support of Shanghai Sailing Program (No. 19YF1422300), Sponsor from Startup Fund for Yongman Research at SJTU (No. 18X100040044) and Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument (No. 15DZ2252000) are also acknowledged.
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