Synthesis of Cisplatin(IV) Prodrug-Tethered CuFeS2 Nanoparticles in Tumor-Targeted Chemotherapy and Photothermal Therapy

In this study, for the first time, CuFeS2 nanocrystals were successfully prepared through a facile noninjection-based synthetic strategy, by reacting Cu and Fe precursors with dodecanethiol in a 1-octadecene solvent. This one-pot noninjection strategy features easy handling, large-scale production, and high synthetic reproducibility. Following hyaluronic acid (HA) encapsulation, CuFeS2 nanocrystals coated with HA (CuFeS2@HA) not only readily dispersed in water and showed improved biocompatibility but also possessed a tumor-specific targeting ability of cancer cells bearing the cluster determinant 44 (CD44) receptors. The encapsulated CuFeS2@HA showed broad optical absorbance from the visible to the near-infrared (NIR) region and high photothermal conversion efficiencies of about 74.2%. They can, therefore, be utilized for the photothermal ablation of cancer cells with NIR light irradiation. In addition, toxicity studies in vitro (B16F1 and HeLa) and in vivo (zebrafish embryos), as well as in vitro blood compatibility studies, indicated that CuFeS2@HA show low cytotoxicity at the doses required for photothermal therapy. More importantly, CuFeS2@HA can be used as delivery vehicles for chemotherapy cisplatin(IV) prodrug forming CuFeS2@HA-Pt(IV). Their release profile revealed pH- and glutathione-mediated drug release from CuFeS2@HA-Pt(IV), which may minimize the side effects of the drug to normal tissues during therapy. Subsequent in vitro experiments confirmed that the use of CuFeS2@HA-Pt(IV) provides an enhanced and synergistic therapeutic effect compared to that from the use of either chemotherapy or photothermal therapy alone.