Assessment of Copper Nanoclusters for Accurate in Vivo Tumor Imaging and Potential for Translation

Gyu Seong Heo, Yongfeng Zhao, Deborah Sultan, Xiaohui Zhang, Lisa Detering, Hannah P. Luehmann, Xiangyu Zhang, Richen Li, Ankur Choksi, Savannah Sharp, Sidney Levingston, Tina Primeau, David E. Reichert, Guorong Sun, Babak Razani, Shunqiang Li, Katherine N. Weilbaecher, Farrokh Dehdashti, Karen L. Wooley, Yongjian Liu

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

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.

Original languageEnglish
Pages (from-to)19669-19678
Number of pages10
JournalACS Applied Materials and Interfaces
Volume11
Issue number22
DOIs
StatePublished - Jun 5 2019

Keywords

  • CXCR4
  • breast cancer
  • copper nanocluster
  • positron emission tomography
  • translation

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