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

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....

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Published in:ACS applied materials & interfaces 2019-06, Vol.11 (22), p.19669-19678
Main Authors: Heo, Gyu Seong, Zhao, Yongfeng, Sultan, Deborah, Zhang, Xiaohui, Detering, Lisa, Luehmann, Hannah P, Zhang, Xiangyu, Li, Richen, Choksi, Ankur, Sharp, Savannah, Levingston, Sidney, Primeau, Tina, Reichert, David E, Sun, Guorong, Razani, Babak, Li, Shunqiang, Weilbaecher, Katherine N, Dehdashti, Farrokh, Wooley, Karen L, Liu, Yongjian
Format: Article
Language:English
Subjects:
Animals
Breast Neoplasms - diagnostic imaging
Copper - adverse effects
Copper - chemistry
Copper Radioisotopes - chemistry
Drug Carriers - chemistry
Female
Humans
Mice
Nanoparticles - adverse effects
Nanoparticles - chemistry
Peptides, Cyclic - chemistry
Positron-Emission Tomography
Receptors, CXCR4 - metabolism
Triple Negative Breast Neoplasms - diagnostic imaging
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Summary: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.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.8b22752