Single-Atom Gadolinium Nano-Contrast Agents with High Stability for Tumor T1 Magnetic Resonance Imaging.

Gadolinium chelates for tumor magnetic resonance imaging (MRI) face challenges such as inadequate sensitivity, lack of selectivity, and risk of Gd leakage. This study presents a single-atom Gd nano-contrast agent (Gd-SA) that enhances tumor MRI. Isolated Gd atoms coordinated by six N atoms and two O atoms are atomically dispersed on a hollow carbon nanosphere, allowing the maximum utilization of Gd atoms with reduced risk of toxic Gd ion leakage. Owning to the large surface area and fast exchange of relaxed water molecules, Gd-SA shows excellent T1-weighted magnetic resonance enhancement with a r1 value of 11.05 mM-1 s-1 at 7 T, which is 3.6 times that of the commercial gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). In vivo MRI results show that the Gd-SA has a higher spatial resolution and a wider imaging time window for tumors than Gd-DTPA, with low hematological, hepatic, and nephric toxicities. These advantages demonstrate the great potential of single-atom Gd-based nanomaterials as safe, efficient, and long-term MRI contrast agents for cancer diagnosis.

[1]  Dingsheng Wang,et al.  Single-atom cobalt nanozymes promote spinal cord injury recovery by anti-oxidation and neuroprotection , 2023, Nano Research.

[2]  F. Gao,et al.  How to Make Personal Protective Equipment Spontaneously and Continuously Antimicrobial (Incorporating Oxidase-like Catalysts). , 2022, ACS nano.

[3]  Lirong Zheng,et al.  A Bioinspired Five‐Coordinated Single‐Atom Iron Nanozyme for Tumor Catalytic Therapy , 2022, Advanced materials.

[4]  Yadong Li,et al.  Engineering the Local Atomic Environments of Indium Single‐Atom Catalysts for Efficient Electrochemical Production of Hydrogen Peroxide , 2022, Angewandte Chemie International Edition.

[5]  J. Ren,et al.  Self-Adaptive Single-Atom Catalyst Boosting Selective Ferroptosis in Tumor Cells. , 2022, ACS nano.

[6]  J. Gan,et al.  Interfacial-confined coordination to single-atom nanotherapeutics , 2022, Nature Communications.

[7]  Yadong Li,et al.  Engineering Dual Single‐Atom Sites on 2D Ultrathin N‐doped Carbon Nanosheets Attaining Ultra‐Low Temperature Zn‐Air Battery , 2022, Angewandte Chemie International Edition.

[8]  Hao Chen,et al.  H2O2 Self‐Producing Single‐Atom Nanozyme Hydrogels as Light‐Controlled Oxidative Stress Amplifier for Enhanced Synergistic Therapy by Transforming “Cold” Tumors , 2022, Advanced Functional Materials.

[9]  S. Rowe,et al.  Molecular imaging in oncology: Current impact and future directions , 2021, CA: a cancer journal for clinicians.

[10]  Min Gyu Kim,et al.  Moving beyond bimetallic-alloy to single-atom dimer atomic-interface for all-pH hydrogen evolution , 2021, Nature Communications.

[11]  T. Meade,et al.  Magnetic Resonance Imaging of PSMA-Positive Prostate Cancer by a Targeted and Activatable Gd(III) MR Contrast Agent. , 2021, Journal of the American Chemical Society.

[12]  Yanli Zhao,et al.  Single-atom engineering of metal-organic frameworks toward healthcare , 2021, Chem.

[13]  Qiangbin Wang,et al.  Au‐Doped Ag2Te Quantum Dots with Bright NIR‐IIb Fluorescence for In Situ Monitoring of Angiogenesis and Arteriogenesis in a Hindlimb Ischemic Model , 2021, Advanced materials.

[14]  Dan Wang,et al.  Hollow structures as drug carriers: Recognition, response, and release , 2021, Nano Research.

[15]  D. Ling,et al.  Artificially engineered antiferromagnetic nanoprobes for ultra-sensitive histopathological level magnetic resonance imaging , 2021, Nature Communications.

[16]  Qinghua Zhang,et al.  Matching the kinetics of natural enzymes with a single-atom iron nanozyme , 2021, Nature Catalysis.

[17]  Yuen Wu,et al.  A highly accessible copper single-atom catalyst for wound antibacterial application , 2021, Nano Research.

[18]  Chunzhen Yang,et al.  Single Atom Pd Nanozyme for Ferroptosis-Boosted Mild-Temperature Photothermal Therapy. , 2021, Angewandte Chemie.

[19]  Jiatao Zhang,et al.  Catalytic Nanomaterials toward Atomic Levels for Biomedical Applications: From Metal Clusters to Single-Atom Catalysts. , 2021, ACS nano.

[20]  Qiangbin Wang,et al.  Colloidal Alloyed Quantum Dots with Enhanced Photoluminescence Quantum Yield in the NIR-II Window. , 2021, Journal of the American Chemical Society.

[21]  N. Weiskopf,et al.  Quantitative magnetic resonance imaging of brain anatomy and in vivo histology , 2021, Nature Reviews Physics.

[22]  C. Ronco,et al.  Gadolinium-Based Contrast Media Nephrotoxicity in Kidney Impairment: The Physio-Pathological Conditions for the Perfect Murder , 2021, Journal of clinical medicine.

[23]  D. Ling,et al.  An Ultrahigh‐Field‐Tailored T1–T2 Dual‐Mode MRI Contrast Agent for High‐Performance Vascular Imaging , 2020, Advanced materials.

[24]  Yadong Li,et al.  Synthetic strategies of supported atomic clusters for heterogeneous catalysis , 2020, Nature Communications.

[25]  Z. Gu,et al.  Functional gadolinium-based nanoscale systems for cancer theranostics. , 2020, Journal of controlled release : official journal of the Controlled Release Society.

[26]  Di Wu,et al.  Single-atom nanozymes: A rising star for biosensing and biomedicine , 2020, Coordination Chemistry Reviews.

[27]  Z. Gu,et al.  Engineered gadolinium-based nanomaterials as cancer imaging agents , 2020 .

[28]  Qiangbin Wang,et al.  Advanced Fluorescence Imaging Technology in the Near-Infrared-II Window for Biomedical Applications. , 2020, Journal of the American Chemical Society.

[29]  Heliang Yao,et al.  Bioinspired Copper Single‐Atom Catalysts for Tumor Parallel Catalytic Therapy , 2020, Advanced materials.

[30]  Shuangyan Huan,et al.  Manganese–Fluorouracil Metallodrug Nanotheranostic for MRI-Correlated Drug Release and Enhanced Chemoradiotherapy , 2020 .

[31]  Yadong Li,et al.  Modulating the local coordination environment of single-atom catalysts for enhanced catalytic performance , 2020, Nano Research.

[32]  X. Qu,et al.  An Enzyme‐Mimicking Single‐Atom Catalyst as an Efficient Multiple Reactive Oxygen and Nitrogen Species Scavenger for Sepsis Management , 2020 .

[33]  Chunsheng Wu,et al.  Engineering the surface of Gd2O3 nanoplates for improved T1-weighted magnetic resonance imaging , 2020 .

[34]  Yu Chen,et al.  Single‐Atom Catalysts in Catalytic Biomedicine , 2020, Advanced materials.

[35]  Jeroen J. Bax,et al.  Assessment of mitral valve regurgitation by cardiovascular magnetic resonance imaging , 2019, Nature Reviews Cardiology.

[36]  Yuehe Lin,et al.  Single-Atom Nanozyme Based on Nanoengineered Fe-N-C Catalyst with Superior Peroxidase-Like Activity for Ultrasensitive Bioassays. , 2019, Small.

[37]  Chengzhou Zhu,et al.  When Nanozymes Meet Single‐Atom Catalysis , 2019, Angewandte Chemie.

[38]  T. Meade,et al.  Molecular MR Imaging with Gd(III)-based Agents: Challenges and Key Advances. , 2019, Journal of the American Chemical Society.

[39]  Yadong Li,et al.  Bismuth Single Atoms Resulting from Transformation of Metal-Organic Frameworks and Their Use as Electrocatalysts for CO2 Reduction. , 2019, Journal of the American Chemical Society.

[40]  Wei Long,et al.  A Nanozyme-Based Bandage with Single-Atom Catalysis for Brain Trauma. , 2019, ACS nano.

[41]  J. Bulte,et al.  Furin-Mediated Intracellular Self-Assembly of Olsalazine Nanoparticles for Enhanced Magnetic Resonance Imaging and Tumor Therapy , 2019, Nature Materials.

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

[43]  P. Netti,et al.  Water-Mediated Nanostructures for Enhanced MRI: Impact of Water Dynamics on Relaxometric Properties of Gd-DTPA , 2019, Theranostics.

[44]  Jianlin Shi,et al.  Nanocatalytic Tumor Therapy by Single-Atom Catalysts. , 2019, ACS nano.

[45]  C. Kuhl.  Abbreviated Magnetic Resonance Imaging (MRI) for Breast Cancer Screening: Rationale, Concept, and Transfer to Clinical Practice. , 2019, Annual review of medicine.

[46]  P. Caravan,et al.  Chemistry of MRI Contrast Agents: Current Challenges and New Frontiers. , 2018, Chemical reviews.

[47]  O. Ciccarelli,et al.  The current role of MRI in differentiating multiple sclerosis from its imaging mimics , 2018, Nature Reviews Neurology.

[48]  Ian D. McGilvray,et al.  Mechanism of hard nanomaterial clearance by the liver , 2016, Nature materials.

[49]  I. Aoki,et al.  Hybrid Calcium Phosphate-Polymeric Micelles Incorporating Gadolinium Chelates for Imaging-Guided Gadolinium Neutron Capture Tumor Therapy. , 2015, ACS nano.

[50]  C. Platas‐Iglesias,et al.  Toward the Prediction of Water Exchange Rates in Magnetic Resonance Imaging Contrast Agents: A Density Functional Theory Study. , 2015, The journal of physical chemistry. A.

[51]  Teri W. Odom,et al.  High relaxivity Gd(III)-DNA gold nanostars: investigation of shape effects on proton relaxation. , 2015, ACS nano.

[52]  Zipeng Zhen,et al.  Gd‐Encapsulated Carbonaceous Dots with Efficient Renal Clearance for Magnetic Resonance Imaging , 2014, Advanced materials.

[53]  Marie C. Heffern,et al.  Lanthanide probes for bioresponsive imaging. , 2014, Chemical reviews.

[54]  H. Kong,et al.  A polymeric fastener can easily functionalize liposome surfaces with gadolinium for enhanced magnetic resonance imaging. , 2013, ACS nano.

[55]  Enzo Terreno,et al.  Challenges for molecular magnetic resonance imaging. , 2010, Chemical reviews.

[56]  P. Perriat,et al.  Hybrid gadolinium oxide nanoparticles: multimodal contrast agents for in vivo imaging. , 2007, Journal of the American Chemical Society.

[57]  Yuen Wu,et al.  Stimuli‐Responsive Manganese Single‐Atom Nanozyme for Tumor Therapy via Integrated Cascade Reactions , 2022, Angewandte Chemie.