Transferrin–Copper Nanocluster–Doxorubicin Nanoparticles as Targeted Theranostic Cancer Nanodrug
2018
Goswami, Upashi | Dutta, Anushree | Raza, Asif | Kandimalla, Raghuram | Kalita, Sanjeeb | Ghosh, Siddhartha Sankar | Chattopadhyay, Arun
Transferrin (Tf)-templated luminescent blue copper nanoclusters (Tf-Cu NCs) are synthesized. They are further formulated into spherical Tf-Cu NC–doxorubicin nanoparticles (Tf-Cu NC–Dox NPs) based on electrostatic interaction with doxorubicin (Dox). The as-synthesized Tf-Cu NC–Dox NPs are explored for bioimaging and targeted drug delivery to delineate high therapeutic efficacy. Förster resonance energy transfer (FRET) within the Tf-Cu NC–Dox 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 NC–Dox 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 NC–Dox 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.
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