Transferrin-Copper Nanocluster-Doxorubicin Nanoparticles as Targeted Theranostic Cancer Nanodrug

Transferrin (Tf)-templated luminescent blue copper nanoclusters (Tf-Cu NCs) are synthesized. They are further formulated into spherical Tf-Cu NCdoxorubicin nanoparticles (Tf-Cu NCDox NPs) based on electrostatic interaction with doxorubicin (Dox). The as-synthesized Tf-Cu NCDox NPs are explored for bioimaging and targeted drug delivery to delineate high therapeutic efficacy. Forster resonance energy transfer (FRET) within the Tf-Cu NCDox NPs exhibited striking red luminescence, wherein the blue luminescence of Tf-Cu NCs (donor) is quenched due to absorption by Dox (acceptor). Interestingly, blue luminescence of Tf-Cu NCs is restored in the cytoplasm of cancer cells upon internalization of the NPs through overexpressed transferrin receptor (TfR) present on the cell surface. Finally, gradual release of Dox from the NPs leads to the generation of its red luminescence inside the nucleus. The biocompatible Tf-Cu NCDox NPs displayed superior targeting efficiency on TfR overexpressed cells (HeLa and MCF-7) as compared to the cells expressing less TfR (HEK-293 and 3T3-L1). Combination index (CI) revealed synergistic activity of Tf-Cu NCs and Dox in Tf-Cu NCDox NPs. In vivo assessment of the NPs on TfR positive Daltons lymphoma ascites (DLA) bearing mice revealed significant inhibition of tumor growth rendering prolonged survival of the mice.