A Tumor‐Microenvironment‐Activated Nanozyme‐Mediated Theranostic Nanoreactor for Imaging‐Guided Combined Tumor Therapy

Activatable theranostic agents that can be activated by tumor microenvironment possess higher specificity and sensitivity. Here, activatable nanozyme‐mediated 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) loaded ABTS@MIL‐100/poly(vinylpyrrolidine) (AMP) nanoreactors (NRs) are developed for imaging‐guided combined tumor therapy. The as‐constructed AMP NRs can be specifically activated by the tumor microenvironment through a nanozyme‐mediated “two‐step rocket‐launching‐like” process to turn on its photoacoustic imaging signal and photothermal therapy (PTT) function. In addition, simultaneously producing hydroxyl radicals in response to the high H2O2 level of the tumor microenvironment and disrupting intracellular glutathione (GSH) endows the AMP NRs with the ability of enhanced chemodynamic therapy (ECDT), thereby leading to more efficient therapeutic outcome in combination with tumor‐triggered PTT. More importantly, the H2O2‐activated and acid‐enhanced properties enable the AMP NRs to be specific to tumors, leaving the normal tissues unharmed. These remarkable features of AMP NRs may open a new avenue to explore nanozyme‐involved nanoreactors for intelligent, accurate, and noninvasive cancer theranostics.

[1]  Xinghua Shi,et al.  A Single-Atom Nanozyme for Wound Disinfection Applications. , 2019, Angewandte Chemie.

[2]  A. Tang,et al.  Exosome-like Nanozyme Vesicles for H2O2-Responsive Catalytic Photoacoustic Imaging of Xenograft Nasopharyngeal Carcinoma. , 2018, Nano letters.

[3]  Qiao Jiang,et al.  Precise nanomedicine for intelligent therapy of cancer , 2018, Science China Chemistry.

[4]  Xin Liu,et al.  MR imaging tracking of inflammation-activatable engineered neutrophils for targeted therapy of surgically treated glioma , 2018, Nature Communications.

[5]  Xuesi Chen,et al.  Engineering Metal-Organic Frameworks for Photoacoustic Imaging-Guided Chemo-/Photothermal Combinational Tumor Therapy. , 2018, ACS applied materials & interfaces.

[6]  Hongyuan Chen,et al.  Engineering of Electrochromic Materials as Activatable Probes for Molecular Imaging and Photodynamic Therapy. , 2018, Journal of the American Chemical Society.

[7]  Feihe Huang,et al.  A discrete organoplatinum(II) metallacage as a multimodality theranostic platform for cancer photochemotherapy , 2018, Nature Communications.

[8]  X. Qu,et al.  Erythrocyte Membrane Cloaked Metal-Organic Framework Nanoparticle as Biomimetic Nanoreactor for Starvation-Activated Colon Cancer Therapy. , 2018, ACS nano.

[9]  Jiye Shi,et al.  Hydrogen Sulfide-Activatable Second Near-Infrared Fluorescent Nanoassemblies for Targeted Photothermal Cancer Therapy. , 2018, Nano letters.

[10]  B. Chang,et al.  BSA-CuS Nanoparticles for Photothermal Therapy of Diabetic Wound Infection In Vivo , 2018, ChemistrySelect.

[11]  D. George,et al.  Leveraging γ-Glutamyl Transferase To Direct Cytotoxicity of Copper Dithiocarbamates against Prostate Cancer Cells. , 2018, Angewandte Chemie.

[12]  X. Qu,et al.  Biomimetic nanoflowers by self-assembly of nanozymes to induce intracellular oxidative damage against hypoxic tumors , 2018, Nature Communications.

[13]  Xuesi Chen,et al.  Multifunctional Theranostic Nanoparticles Derived from Fruit-Extracted Anthocyanins with Dynamic Disassembly and Elimination Abilities. , 2018, ACS nano.

[14]  Taeghwan Hyeon,et al.  Responsive Assembly of Upconversion Nanoparticles for pH‐Activated and Near‐Infrared‐Triggered Photodynamic Therapy of Deep Tumors , 2018, Advanced materials.

[15]  Kanyi Pu,et al.  Macrotheranostic Probe with Disease-Activated Near-Infrared Fluorescence, Photoacoustic, and Photothermal Signals for Imaging-Guided Therapy. , 2018, Angewandte Chemie.

[16]  W. Liu,et al.  Highly stable molybdenum dioxide nanoparticles with strong plasmon resonance are promising in photothermal cancer therapy. , 2018, Biomaterials.

[17]  Xuesi Chen,et al.  Gold Nanorods Electrostatically Binding Nucleic Acid Probe for In Vivo MicroRNA Amplified Detection and Photoacoustic Imaging‐Guided Photothermal Therapy , 2018 .

[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]  Lizeng Gao,et al.  In vivo guiding nitrogen-doped carbon nanozyme for tumor catalytic therapy , 2018, Nature Communications.

[20]  Kanyi Pu,et al.  Temperature-Correlated Afterglow of a Semiconducting Polymer Nanococktail for Imaging-Guided Photothermal Therapy. , 2018, Angewandte Chemie.

[21]  Wenbo Wu,et al.  Metal–Organic Framework as a Simple and General Inert Nanocarrier for Photosensitizers to Implement Activatable Photodynamic Therapy , 2018 .

[22]  Kenry,et al.  Metal–Organic‐Framework‐Assisted In Vivo Bacterial Metabolic Labeling and Precise Antibacterial Therapy , 2018, Advanced materials.

[23]  Xiaoying Tang,et al.  Polyrotaxane-based supramolecular theranostics , 2018, Nature Communications.

[24]  Mingyuan Gao,et al.  Enhancing Both Biodegradability and Efficacy of Semiconducting Polymer Nanoparticles for Photoacoustic Imaging and Photothermal Therapy. , 2018, ACS nano.

[25]  Junjie Deng,et al.  Tumor targeted, stealthy and degradable bismuth nanoparticles for enhanced X-ray radiation therapy of breast cancer. , 2018, Biomaterials.

[26]  X. Qu,et al.  Nanozyme Decorated Metal-Organic Frameworks for Enhanced Photodynamic Therapy. , 2018, ACS nano.

[27]  Jinping Wang,et al.  All-in-One Theranostic Nanoplatform Based on Hollow MoSx for Photothermally-maneuvered Oxygen Self-enriched Photodynamic Therapy , 2018, Theranostics.

[28]  Dan Ding,et al.  Chemiluminescence-Guided Cancer Therapy Using a Chemiexcited Photosensitizer , 2017 .

[29]  Dong Yun Lee,et al.  Black Pigment Gallstone Inspired Platinum-Chelated Bilirubin Nanoparticles for Combined Photoacoustic Imaging and Photothermal Therapy of Cancers. , 2017, Angewandte Chemie.

[30]  Kanyi Pu,et al.  Nanoparticle Regrowth Enhances Photoacoustic Signals of Semiconducting Macromolecular Probe for In Vivo Imaging , 2017, Advanced materials.

[31]  Yu Chen,et al.  Tumor-selective catalytic nanomedicine by nanocatalyst delivery , 2017, Nature Communications.

[32]  Lizeng Gao,et al.  Iron Oxide Nanozyme: A Multifunctional Enzyme Mimetic for Biomedical Applications , 2017, Theranostics.

[33]  Dehong Hu,et al.  Theranostic gold cluster nanoassembly for simultaneous enhanced cancer imaging and photodynamic therapy , 2017 .

[34]  Youxun Liu,et al.  Stable ABTS Immobilized in the MIL-100(Fe) Metal-Organic Framework as an Efficient Mediator for Laccase-Catalyzed Decolorization , 2017, Molecules.

[35]  Xiu‐Ping Yan,et al.  Dual-stimuli responsive and reversibly activatable theranostic nanoprobe for precision tumor-targeting and fluorescence-guided photothermal therapy , 2017, Nature Communications.

[36]  Liangzhu Feng,et al.  H2O2-responsive liposomal nanoprobe for photoacoustic inflammation imaging and tumor theranostics via in vivo chromogenic assay , 2017, Proceedings of the National Academy of Sciences.

[37]  Hong Yang,et al.  Photoconversion‐Tunable Fluorophore Vesicles for Wavelength‐Dependent Photoinduced Cancer Therapy , 2017, Advanced materials.

[38]  Abolfazl Akbarzadeh,et al.  Nanozyme applications in biology and medicine: an overview , 2017, Artificial cells, nanomedicine, and biotechnology.

[39]  Lei Wang,et al.  Metal–Organic Framework@Porous Organic Polymer Nanocomposite for Photodynamic Therapy , 2017 .

[40]  Guonan Chen,et al.  High peroxidase-like activity of iron and nitrogen co-doped carbon dots and its application in immunosorbent assay. , 2017, Talanta.

[41]  Paul Kumar Upputuri,et al.  Self-quenched semiconducting polymer nanoparticles for amplified in vivo photoacoustic imaging. , 2017, Biomaterials.

[42]  S. Dong,et al.  One-Pot Synthesis of Fe3O4 Nanoparticle Loaded 3D Porous Graphene Nanocomposites with Enhanced Nanozyme Activity for Glucose Detection. , 2017, ACS applied materials & interfaces.

[43]  Yan Zhang,et al.  One-step analysis of glucose and acetylcholine in water based on the intrinsic peroxidase-like activity of Ni/Co LDHs microspheres. , 2017, Journal of materials chemistry. B.

[44]  Qiwen Chen,et al.  Recent advances in different modal imaging-guided photothermal therapy. , 2016, Biomaterials.

[45]  Xiaogang Qu,et al.  Metal‐Organic‐Framework‐Based Vaccine Platforms for Enhanced Systemic Immune and Memory Response , 2016 .

[46]  Liangzhu Feng,et al.  Intelligent Albumin–MnO2 Nanoparticles as pH‐/H2O2‐Responsive Dissociable Nanocarriers to Modulate Tumor Hypoxia for Effective Combination Therapy , 2016, Advanced materials.

[47]  Lizeng Gao,et al.  Nanozymes: an emerging field bridging nanotechnology and biology , 2016, Science China Life Sciences.

[48]  Zhigang Xie,et al.  One-Step Synthesis of Nanoscale Zeolitic Imidazolate Frameworks with High Curcumin Loading for Treatment of Cervical Cancer. , 2015, ACS applied materials & interfaces.

[49]  Jong Seung Kim,et al.  Small conjugate-based theranostic agents: an encouraging approach for cancer therapy. , 2015, Chemical Society reviews.

[50]  G. Mugesh,et al.  An antioxidant nanozyme that uncovers the cytoprotective potential of vanadia nanowires , 2014, Nature Communications.

[51]  Chunying Chen,et al.  Near‐Infrared Light‐Mediated Nanoplatforms for Cancer Thermo‐Chemotherapy and Optical Imaging , 2013, Advanced materials.

[52]  Yingsheng Cheng,et al.  Effective reduction of nonspecific binding by surface engineering of quantum dots with bovine serum albumin for cell-targeted imaging. , 2012, Langmuir : the ACS journal of surfaces and colloids.

[53]  Haiyan Cao,et al.  Peroxidase-like activity of chitosan stabilized silver nanoparticles for visual and colorimetric detection of glucose. , 2012, The Analyst.

[54]  Jiajia Wu,et al.  Manganese oxide nanowire-mediated enzyme-linked immunosorbent assay. , 2012, Biosensors & bioelectronics.

[55]  C. Huang,et al.  Visual observation of the mercury-stimulated peroxidase mimetic activity of gold nanoparticles. , 2011, Chemical communications.

[56]  Zhi Shan,et al.  BSA-stabilized Au clusters as peroxidase mimetics for use in xanthine detection. , 2011, Biosensors & bioelectronics.

[57]  W. Tremel,et al.  V2O5 Nanowires with an Intrinsic Peroxidase‐Like Activity , 2011 .

[58]  Y. Liu,et al.  Au@Pt nanostructures as oxidase and peroxidase mimetics for use in immunoassays. , 2011, Biomaterials.

[59]  E. Wang,et al.  Monodisperse mesoporous superparamagnetic single-crystal magnetite nanoparticles for drug delivery. , 2009, Biomaterials.

[60]  S. Dong,et al.  Magnet-assisted assembly of 1-dimensional hollow PtCo nanomaterials on an electrode surface , 2008 .

[61]  Yu Zhang,et al.  Intrinsic peroxidase-like activity of ferromagnetic nanoparticles. , 2007, Nature nanotechnology.

[62]  B. Kalyanaraman,et al.  Detection of thiyl radical adducts formed during hydroxyl radical- and peroxynitrite-mediated oxidation of thiols--a high resolution ESR spin-trapping study at Q-band (35 GHz). , 1996, Analytical biochemistry.

[63]  C. Winterbourn Toxicity of iron and hydrogen peroxide: the Fenton reaction. , 1995, Toxicology letters.

[64]  C. Nathan,et al.  Production of large amounts of hydrogen peroxide by human tumor cells. , 1991, Cancer research.

[65]  S. Linn,et al.  Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro. , 1988, Science.

[66]  L. Oberley,et al.  Considerations in the spin trapping of superoxide and hydroxyl radical in aqueous systems using 5,5-dimethyl-1-pyrroline-1-oxide. , 1978, Biochemical and biophysical research communications.