Chelator-Free Conjugation of 99mTc and Gd3+ to PEGylated Nanographene Oxide for Dual-Modality SPECT/MR Imaging of Lymph Nodes.

PEGylated ultrasmall nanographene oxide (usNGO-PEG) has exhibited a great potential in nanotheranostics due to its newly discovered physicochemical properties derived from the rich functional groups and bonds. Herein, we developed a general, simple, and kitlike preparation approach for 99mTc- and Gd-anchored NGO-PEG using a chelator-free strategy. In this strategy, [99mTcI(CO)3(OH2)3]+ (abbreviated to 99mTcI) and GdCl3 were mixed with usNGO-PEG to yield 99mTc- and Gd-usNGO-PEG via the synergistic coordination of N and O atoms from NGO and PEG with 99mTcI and Gd3+ without additional exogenous chelators. Under optimized conditions, the nanoprobes 99mTc- and Gd-usNGO-PEG were reliably prepared with high yields and good stability. Serial comparative experiments of the labeling yield, the measurements of -NH2 density and ζ-potentials, and various characterizations including energy-dispersive X-ray analysis spectroscopy, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy demonstrated that both usNGO and PEG synergistically provide the electron-donating atoms O and N to coordinate with 99mTcI and Gd to form stable nanocomplexes. Furthermore, both 99mTc- and Gd-usNGO-PEG exhibited excellent in vivo imaging of lymph nodes using single-photon emission computed tomography/computed tomography (SPECT/CT) and magnetic resonance (MR) imaging after local injection. Therefore, these results showed the successful establishment of 99mTc- and Gd-anchored usNGO-PEG using a chelator-free strategy and the potential of multimodality SPECT/CT and MR imaging of lymph nodes.

[1]  Bengang Xing,et al.  Nanostructures for NIR light-controlled therapies. , 2017, Nanoscale.

[2]  P. E. Hare,et al.  O-phthalaldehyde: fluorogenic detection of primary amines in the picomole range. Comparison with fluorescamine and ninhydrin. , 1975, Proceedings of the National Academy of Sciences of the United States of America.

[3]  V. Trubetskoy,et al.  Polymeric micelles as carriers of diagnostic agents. , 1999, Advanced Drug Delivery Reviews.

[4]  Zhe Wang,et al.  Photosensitizer Loaded Nano-Graphene for Multimodality Imaging Guided Tumor Photodynamic Therapy , 2014, Theranostics.

[5]  Byung Hee Hong,et al.  Graphene-based nanomaterials for versatile imaging studies. , 2015, Chemical Society reviews.

[6]  Jan Grimm,et al.  Non-invasive mapping of deep-tissue lymph nodes in live animals using a multimodal PET/MRI nanoparticle , 2014, Nature Communications.

[7]  W. Ran,et al.  Recent Progress in Light-Triggered Nanotheranostics for Cancer Treatment , 2016, Theranostics.

[8]  Marco Orecchioni,et al.  Graphene as Cancer Theranostic Tool: Progress and Future Challenges , 2015, Theranostics.

[9]  Feng Chen,et al.  Intrinsic and Stable Conjugation of Thiolated Mesoporous Silica Nanoparticles with Radioarsenic. , 2017, ACS applied materials & interfaces.

[10]  Hong Yang,et al.  Visualization of size-dependent tumour retention of PEGylated nanographene oxide via SPECT imaging. , 2016, Journal of materials chemistry. B.

[11]  R. Lauffer,et al.  Gadolinium(III) Chelates as MRI Contrast Agents: Structure, Dynamics, and Applications. , 1999, Chemical reviews.

[12]  Yu Li,et al.  Easy preparation of an MRI contrast agent with high longitudinal relaxivity based on gadolinium ions-loaded graphene oxide , 2014 .

[13]  Yongmin Chang,et al.  Heteronuclear Gd-(99m)Tc Complex of DTPA-Bis(histidylamide) Conjugate as a Bimodal MR/SPECT Imaging Probe. , 2012, ACS medicinal chemistry letters.

[14]  Kai Yang,et al.  Nano-graphene in biomedicine: theranostic applications. , 2013, Chemical Society reviews.

[15]  Yongjun Li,et al.  Covalent functionalization of graphene oxide with biocompatible poly(ethylene glycol) for delivery of paclitaxel. , 2014, ACS applied materials & interfaces.

[16]  Roger Schibli,et al.  A Novel Organometallic Aqua Complex of Technetium for the Labeling of Biomolecules: Synthesis of [99mTc(OH2)3(CO)3]+ from [99mTcO4]- in Aqueous Solution and Its Reaction with a Bifunctional Ligand , 1998 .

[17]  T. Hoffman,et al.  Therapeutic radiopharmaceuticals. , 1999, Chemical reviews.

[18]  Weibo Cai,et al.  Positron emission tomography imaging using radiolabeled inorganic nanomaterials. , 2015, Accounts of chemical research.

[19]  YingJian Zhang,et al.  Optimization of Early Response Monitoring and Prediction of Cancer Antiangiogenesis Therapy via Noninvasive PET Molecular Imaging Strategies of Multifactorial Bioparameters , 2016, Theranostics.

[20]  H. Dai,et al.  Carbon Nanomaterials for Biological Imaging and Nanomedicinal Therapy. , 2015, Chemical reviews.

[21]  Jingliang Cheng,et al.  Facile synthesis of gadolinium (III) chelates functionalized carbon quantum dots for fluorescence and magnetic resonance dual-modal bioimaging , 2015 .

[22]  O. Shenderova,et al.  Functionalization of graphene oxide nanostructures improves photoluminescence and facilitates their use as optical probes in preclinical imaging. , 2015, Nanoscale.

[23]  K. Alitalo,et al.  Lymphangiogenesis: Molecular Mechanisms and Future Promise , 2010, Cell.

[24]  Jae-Young Choi,et al.  Efficient Reduction of Graphite Oxide by Sodium Borohydride and Its Effect on Electrical Conductance , 2009 .

[25]  Hung-Wei Yang,et al.  Gadolinium-functionalized nanographene oxide for combined drug and microRNA delivery and magnetic resonance imaging. , 2014, Biomaterials.

[26]  Sverre Myhra,et al.  Nanographene oxide-based radioimmunoconstructs for in vivo targeting and SPECT imaging of HER2-positive tumors. , 2013, Biomaterials.

[27]  Gang Liu,et al.  Imaging-guided delivery of RNAi for anticancer treatment. , 2016, Advanced drug delivery reviews.

[28]  Hanno Schieferstein,et al.  Radiolabeling of Nanoparticles and Polymers for PET Imaging , 2014, Pharmaceuticals.

[29]  Feng Chen,et al.  Engineering of radiolabeled iron oxide nanoparticles for dual-modality imaging. , 2016, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[30]  Yan Xing,et al.  Radiolabeled Nanoparticles for Multimodality Tumor Imaging , 2014, Theranostics.

[31]  Weibo Cai,et al.  Facile Preparation of Multifunctional WS2 /WOx Nanodots for Chelator-Free 89 Zr-Labeling and In Vivo PET Imaging. , 2016, Small.

[32]  Kai Yang,et al.  In vivo targeting and imaging of tumor vasculature with radiolabeled, antibody-conjugated nanographene. , 2012, ACS nano.

[33]  S. Stacker,et al.  Lymphangiogenesis and lymphatic vessel remodelling in cancer , 2014, Nature Reviews Cancer.

[34]  Dong Soo Lee,et al.  Radionanomedicine: widened perspectives of molecular theragnosis. , 2015, Nanomedicine : nanotechnology, biology, and medicine.

[35]  Bin Tang,et al.  A review of optical imaging and therapy using nanosized graphene and graphene oxide. , 2013, Biomaterials.

[36]  Juan Li,et al.  Adaption of the structure of carbon nanohybrids toward high-relaxivity for a new MRI contrast agent , 2016 .

[37]  Feng Chen,et al.  Intrinsically radiolabeled nanoparticles: an emerging paradigm. , 2014, Small.

[38]  Nurunnabi,et al.  Bioapplication of graphene oxide derivatives: drug/gene delivery, imaging, polymeric modification, toxicology, therapeutics and challenges , 2015 .

[39]  Jan Grimm,et al.  Silica Nanoparticles as Substrates for Chelator-free Labeling of Oxophilic Radioisotopes , 2015, Nano letters.

[40]  Peng Huang,et al.  Graphene-based nanomaterials for bioimaging. , 2016, Advanced drug delivery reviews.

[41]  Kai Yang,et al.  Chelator-Free Radiolabeling of Nanographene: Breaking the Stereotype of Chelation. , 2017, Angewandte Chemie.

[42]  Liangzhu Feng,et al.  Comparison of nanomedicine-based chemotherapy, photodynamic therapy and photothermal therapy using reduced graphene oxide for the model system. , 2017, Biomaterials science.

[43]  Heather M. Hennkens,et al.  Radiometals for combined imaging and therapy. , 2013, Chemical reviews.

[44]  Hao Hong,et al.  In vivo targeting and positron emission tomography imaging of tumor vasculature with (66)Ga-labeled nano-graphene. , 2012, Biomaterials.