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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.


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GSH-triggered sequential catalysis for tumor imaging and eradication based on star-like Au/Pt enzyme carrier system

Show Author's information Amin Zhang1,2Qian Zhang1,2Gabriel Alfranca1,4Shaojun Pan2,3Zhicheng Huang1,2Jin Cheng1,2Qiang Ma5Jie Song1,2Yunxiang Pan1,2Jian Ni1,2Lijun Ma6( )Daxiang Cui1,2,3( )
Institute of Nano Biomedicine and Engineering, Shanghai Engineering Research Center for Intelligent Diagnosis and Treatment Instrument, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, 800 Dongchuan RD, Shanghai 200240, China
National Center for Translational Medicine, Collaborative Innovational Center for System Biology, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China
School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China
Instituto de Ciencia de Materiales de Aragón (ICMA), CSIC/Universidad de Zaragoza, C/Pedro Cerbuna 12, 50009 Zaragoza, Spain
Department of Tumor, Xintai People's Hospital, Xintai 271200, China
Department of Tumor in Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai 200336, China

Abstract

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.

Keywords: peroxidase, Au/Pt star, GSH-responsive, GOx, sequential nanocatalyst, cancer starving-like therapy, enzyme oxidative therapy, photo-thermal therapy & photodynamic therapy (PTT&PDT)

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Publication history
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Acknowledgements

Publication history

Received: 10 October 2019
Revised: 24 November 2019
Accepted: 29 November 2019
Published: 02 January 2020
Issue date: January 2020

Copyright

© Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Acknowledgements

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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