Paclitaxel-Loaded Biotinylated Fe2+-Doped Carbon Dot: Combination Therapy in Cancer Treatment.

The present research work delineates the design and preparation of covalently tailored biotinylated Fe2+-doped carbon dots (FCDb). The FCDb was successfully used as a pro-drug activator, diagnostic probe, and target-specific delivery vehicle for anticancer drug paclitaxel in pro-drug-free drug combination therapy of cancer treatment. Fe2+-doped carbon dot was synthesized via the hydrothermal method (FCD). The surface of FCD was covalently modified with cancer cell targeting ligand biotin (FCDb). Microscopic and spectroscopic methods were used to characterize aqueous soluble FCD and FCDb. Both FCD and FCDb emit blue fluorescence under UV light irradiation. FCD and FCDb can effectively sense H2O2 by fluorescence quenching as well as activate H2O2 (pro-drug), which oxidatively damage the DNA through the generation of reactive oxygen species (ROS: superoxide (O2•-), hydroxyl radical (•OH), etc). Both FCD and FCDb were utilized as selective cellular markers for cancer cell B16F10 owing to their high H2O2 content, which was more distinct in the case of FCDb due to the overexpression of biotin receptor in cancer cell. Anticancer drug paclitaxel (PTX)-loaded FCDb (FCDb-PTX) was employed for the selective killing of B16F10 cancer cells. This pro-drug-free drug formulation (FCDb-PTX) exhibited ∼2.7- to 3.5-fold higher killing of B16F10 cells mostly via early as well as late apoptotic path in comparison to noncancer NIH3T3 cells through the synergistic action of ROS (generated from H2O2 in the presence of FCDb) and anticancer effect of PTX. Hence, this newly developed FCDb-PTX can act as a potential theranostic agent in the domain of combination therapy of cancer treatment.