GSH‐Depleted PtCu3 Nanocages for Chemodynamic‐ Enhanced Sonodynamic Cancer Therapy

The ultrahigh concentration of glutathione (GSH) inside tumors destroys reactive oxygen species (ROS)‐based therapy, improving the outcome of chemodynamic therapy (CDT)‐enhanced sonodynamic therapy (SDT) by depleting GSH is full of great challenge. Herein, PtCu3 nanocages are first reported as acting as a sonosensitizer with highly efficient ROS generation under ultrasound irradiation. In addition, PtCu3 nanocages can act as horseradish peroxidase‐like nanozymes, catalyzing the decomposition of H2O2 into •OH under acidic conditions for CDT. Surprisingly, PtCu3 nanocages can act as another kind of nanozyme, mimicking glutathione peroxidase (GSH‐Px), which plays an important role in accelerating GSH depletion by oxidizing molecules, further weakening the capacity of tumor cells scavenging ROS by GSH. Both in vitro and in vivo studies demonstrate that PtCu3 nanocages perform well in reducing GSH level for CDT‐enhanced SDT. Moreover, utilizing the high absorption in the near‐infrared region and strong X‐ray attenuation ability, the PtCu3 nanocages are able to conduct photoacoustic/computed tomography dual‐modal imaging‐guided combined cancer therapy. It is worth mentioning that PtCu3 nanocages cause minimal toxicity to normal tissues at therapeutic doses. This work highlights the use of PtCu3 nanocages for effective CDT‐enhanced SDT via GSH depletion.

[1]  Yi Sun,et al.  Enhanced Plasmon-Induced Resonance Energy Transfer (PIRET)-mediated Photothermal and Photodynamic Therapy Guided by Photoacoustic and Magnetic Resonance Imaging. , 2019, ACS applied materials & interfaces.

[2]  Zhuang Liu,et al.  Hollow Cu2Se Nanozymes for Tumor Photothermal-Catalytic Therapy , 2019, Chemistry of Materials.

[3]  Xiaolong Shi,et al.  The softness of tumour-cell-derived microparticles regulates their drug-delivery efficiency , 2019, Nature Biomedical Engineering.

[4]  Xiaobing Zhang,et al.  Persistent Regulation of Tumor Microenvironment via Circulating Catalysis of MnFe2O4@Metal–Organic Frameworks for Enhanced Photodynamic Therapy , 2019, Advanced Functional Materials.

[5]  Liangzhu Feng,et al.  Ultrasmall Oxygen‐Deficient Bimetallic Oxide MnWOX Nanoparticles for Depletion of Endogenous GSH and Enhanced Sonodynamic Cancer Therapy , 2019, Advanced materials.

[6]  Yaru Cheng,et al.  Biodegradable Biomimic Copper/Manganese Silicate Nanospheres for Chemodynamic/Photodynamic Synergistic Therapy with Simultaneous Glutathione Depletion and Hypoxia Relief. , 2019, ACS nano.

[7]  Junjie Zhu,et al.  One-Dimensional Fe2 P Acts as a Fenton Agent in Response to NIR II Light and Ultrasound for Deep Tumor Synergetic Theranostics. , 2019, Angewandte Chemie.

[8]  Liangzhu Feng,et al.  Amplification of Tumor Oxidative Stresses with Liposomal Fenton Catalyst and Glutathione Inhibitor for Enhanced Cancer Chemotherapy and Radiotherapy. , 2018, Nano letters.

[9]  Huaqing Chen,et al.  Metalloporphyrin Complex-Based Nanosonosensitizers for Deep-Tissue Tumor Theranostics by Noninvasive Sonodynamic Therapy. , 2019, Small.

[10]  W. Bu,et al.  Chemodynamic Therapy: Tumour Microenvironment-Mediated Fenton and Fenton-like Reactions. , 2018, Angewandte Chemie.

[11]  Feng Liu,et al.  Self-Assembled Copper-Amino Acid Nanoparticles for in Situ Glutathione "AND" H2O2 Sequentially Triggered Chemodynamic Therapy. , 2018, Journal of the American Chemical Society.

[12]  Steve Y. Cho,et al.  Molybdenum-based nanoclusters act as antioxidants and ameliorate acute kidney injury in mice , 2018, Nature Communications.

[13]  Bin Liu,et al.  Recent Advances of Optical Imaging in the Second Near‐Infrared Window , 2018, Advanced materials.

[14]  Zhuang Liu,et al.  Bimetallic Oxide MnMoOX Nanorods for in Vivo Photoacoustic Imaging of GSH and Tumor-Specific Photothermal Therapy. , 2018, Nano letters.

[15]  Can Li,et al.  Charge separation via asymmetric illumination in photocatalytic Cu2O particles , 2018, Nature Energy.

[16]  Chunying Chen,et al.  Synthesis of Pt Hollow Nanodendrites with Enhanced Peroxidase‐Like Activity against Bacterial Infections: Implication for Wound Healing , 2018 .

[17]  Lixin Bai,et al.  Metal–Organic‐Framework‐Derived Carbon Nanostructure Augmented Sonodynamic Cancer Therapy , 2018, Advanced materials.

[18]  Juan Li,et al.  Simultaneous Fenton-like Ion Delivery and Glutathione Depletion by MnO2 -Based Nanoagent to Enhance Chemodynamic Therapy. , 2018, Angewandte Chemie.

[19]  Sunil Sahi,et al.  Nanosonosensitization by Using Copper–Cysteamine Nanoparticles Augmented Sonodynamic Cancer Treatment , 2018, Particle & Particle Systems Characterization.

[20]  Baoquan Ding,et al.  A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo , 2018, Nature Biotechnology.

[21]  H. Wei,et al.  The effect of adding Bi3+ on the performance of a newly developed iron–copper redox flow battery , 2018, RSC advances.

[22]  Hui-Fen Wu,et al.  Shape-oriented photodynamic therapy of cuprous oxide (Cu2O) nanocrystals for cancer treatment , 2017 .

[23]  Jianlin Shi,et al.  Chemical Design and Synthesis of Functionalized Probes for Imaging and Treating Tumor Hypoxia. , 2017, Chemical reviews.

[24]  Han Lin,et al.  Metalloporphyrin-Encapsulated Biodegradable Nanosystems for Highly Efficient Magnetic Resonance Imaging-Guided Sonodynamic Cancer Therapy. , 2017, Journal of the American Chemical Society.

[25]  Peng Huang,et al.  Overcoming the Achilles' heel of photodynamic therapy. , 2016, Chemical Society reviews.

[26]  Yuanyi Zheng,et al.  Micro/Nanoparticle‐Augmented Sonodynamic Therapy (SDT): Breaking the Depth Shallow of Photoactivation , 2016, Advanced materials.

[27]  Xiaogang Qu,et al.  Copper(II)-Graphitic Carbon Nitride Triggered Synergy: Improved ROS Generation and Reduced Glutathione Levels for Enhanced Photodynamic Therapy. , 2016, Angewandte Chemie.

[28]  W. Tan,et al.  A Smart Photosensitizer-Manganese Dioxide Nanosystem for Enhanced Photodynamic Therapy by Reducing Glutathione Levels in Cancer Cells. , 2016, Angewandte Chemie.

[29]  A. Jemal,et al.  Cancer statistics, 2016 , 2016, CA: a cancer journal for clinicians.

[30]  Kai Yang,et al.  Core–Shell MnSe@Bi2Se3 Fabricated via a Cation Exchange Method as Novel Nanotheranostics for Multimodal Imaging and Synergistic Thermoradiotherapy , 2015, Advanced materials.

[31]  Wenpei Fan,et al.  Intelligent MnO2 Nanosheets Anchored with Upconversion Nanoprobes for Concurrent pH‐/H2O2‐Responsive UCL Imaging and Oxygen‐Elevated Synergetic Therapy , 2015, Advanced materials.

[32]  Longfei Tan,et al.  Plasmonic copper sulfide nanocrystals exhibiting near-infrared photothermal and photodynamic therapeutic effects. , 2015, ACS nano.

[33]  K. Soo,et al.  Nanoparticles in photodynamic therapy. , 2015, Chemical reviews.

[34]  Lianzhou Wang,et al.  Break‐up of Two‐Dimensional MnO2 Nanosheets Promotes Ultrasensitive pH‐Triggered Theranostics of Cancer , 2014, Advanced materials.

[35]  Juyoung Yoon,et al.  Cyanine-based fluorescent probe for highly selective detection of glutathione in cell cultures and live mouse tissues. , 2014, Journal of the American Chemical Society.

[36]  Zhuang Liu,et al.  PEGylated Micelle Nanoparticles Encapsulating a Non‐Fluorescent Near‐Infrared Organic Dye as a Safe and Highly‐Effective Photothermal Agent for In Vivo Cancer Therapy , 2013 .

[37]  M. Todaro,et al.  Tumor and its microenvironment: a synergistic interplay. , 2013, Seminars in cancer biology.

[38]  X. Lou,et al.  One-pot synthesis of cubic PtCu3 nanocages with enhanced electrocatalytic activity for the methanol oxidation reaction. , 2012, Journal of the American Chemical Society.

[39]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[40]  S. Seal,et al.  Redox-active radical scavenging nanomaterials. , 2010, Chemical Society reviews.

[41]  Peng Huang,et al.  Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? , 2009, Nature Reviews Drug Discovery.

[42]  M. Ferrari.  Cancer nanotechnology: opportunities and challenges , 2005, Nature Reviews Cancer.

[43]  Samir Mitragotri,et al.  Healing sound: the use of ultrasound in drug delivery and other therapeutic applications , 2005, Nature Reviews Drug Discovery.