@article{b6ced73c660c4f95b0c097594ab4c50b,
title = "Assessment of Copper Nanoclusters for Accurate in Vivo Tumor Imaging and Potential for Translation",
abstract = "Nanoparticles have been widely used for preclinical cancer imaging. However, their successful clinical translation is largely hampered by potential toxicity, unsatisfactory detection of malignancy at early stages, inaccurate diagnosis of tumor biomarkers, and histology for imaging-guided treatment. Herein, a targeted copper nanocluster (CuNC) is reported with high potential to address these challenges for future translation. Its ultrasmall structure enables efficient renal/bowel clearance, minimized off-target effects in nontargeted organs, and low nonspecific tumor retention. The pH-dependent in vivo dissolution of CuNCs affords minimal toxicity and potentially selective drug delivery to tumors. The intrinsic radiolabeling through the direct addition of 64Cu to CuNC (64Cu-CuNCs-FC131) synthesis offers high specific activity for sensitive and accurate detection of CXCR4 via FC131-directed targeting in novel triple negative breast cancer (TNBC) patient-derived xenograft mouse models and human TNBC tissues. In summary, this study not only reveals the potential of CXCR4-targeted 64Cu-CuNCs for TNBC imaging in clinical settings, but also provides a useful strategy to design and assess the translational potential of nanoparticles for cancer theranostics.",
keywords = "CXCR4, breast cancer, copper nanocluster, positron emission tomography, translation",
author = "Heo, {Gyu Seong} and Yongfeng Zhao and Deborah Sultan and Xiaohui Zhang and Lisa Detering and Luehmann, {Hannah P.} and Xiangyu Zhang and Richen Li and Ankur Choksi and Savannah Sharp and Sidney Levingston and Tina Primeau and Reichert, {David E.} and Guorong Sun and Babak Razani and Shunqiang Li and Weilbaecher, {Katherine N.} and Farrokh Dehdashti and Wooley, {Karen L.} and Yongjian Liu",
note = "Funding Information: All animal experiments were carried out in compliance with the institutional animal care and usage committee (IACUC) guidelines of Washington University. De-identified human TNBC specimens were obtained from the Tissue Procurement Core of Siteman Cancer Center under the approval from the Human Research Protection Office of Washington University. This work was partially performed at the Nano Research Facility (NRF), a member of the National Nanotechnology Infrastructure Network (NNIN), which is supported by the National Science Foundation under grant no. ECS-0335765. Any opinions, findings, conclusions, or recommendations expressed in this material are those of the author(s) and do not necessarily reflect the views of the National Science Foundation. NRF is part of the School of Engineering and Applied Science at Washington University in St. Louis. This work was performed with the support from the Siteman Cancer Center Small Animal Imaging Core at Washington University in St. Louis. We thank the staff members from the Washington University cyclotron facility for 64Cu production. The ESI−MS results were acquired by use of the NIH/ NIGMS Biomedical Mass Spectrometry Resource at Washington University in St. Louis, MO, which is supported by National Institutes of Health/National Institute of General Medical Sciences Grant (8P41GM103422). Experiments were performed in part through the use of the Washington University Center for Cellular Imaging (WUCCI) supported by the Washington University School of Medicine, the Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital (CDI-CORE-2015-505), and the National Institute for Neurological Disorders and Stroke (NS086741). The authors acknowledge financial support from Washington University in St. Louis and the Institute of Materials Science and Engineering for the use of instruments and staff assistance. The authors acknowledge the support from the NCI grant (U24-CA209837) for animal models and PET imaging. Publisher Copyright: {\textcopyright} 2019 American Chemical Society.",
year = "2019",
month = jun,
day = "5",
doi = "10.1021/acsami.8b22752",
language = "English",
volume = "11",
pages = "19669--19678",
journal = "ACS Applied Materials and Interfaces",
issn = "1944-8244",
number = "22",
}