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. Herein, a targeted and in vivo degradable 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 non-targeted organs, and low non-specific 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 into CuNC (64Cu-CuNCs) synthesis offers high specific activity for sensitive and accurate detection of CXCR4 in novel triple negative breast cancer (TNBC) patient-derived xenograft mouse models and human TNBC tissues. Taken together, this study not only demonstrates 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.