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 (FCD). The FCD 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 (FCD). Microscopic and spectroscopic methods were used to characterize aqueous soluble FCD and FCD. Both FCD and FCD emit blue fluorescence under UV light irradiation. FCD and FCD 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 FCD were utilized as selective cellular markers for cancer cell B16F10 owing to their high H₂O₂ content, which was more distinct in the case of FCD due to the overexpression of biotin receptor in cancer cell. Anticancer drug paclitaxel (PTX)-loaded FCD (FCD-PTX) was employed for the selective killing of B16F10 cancer cells. This pro-drug-free drug formulation (FCD-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 FCD) and anticancer effect of PTX. Hence, this newly developed FCD-PTX can act as a potential theranostic agent in the domain of combination therapy of cancer treatment.