An innovative red-emitting nickel-doped carbon dot for simultaneous detection of Fe(III) and pyrophosphate ions, coupled with synergistic photothermal/photodynamic cancer therapy.

Background: Multifunctional carbon dots (CDs) have gained prominence in biosensing, cell imaging, and nanomedicine due to their tunable fluorescence, excellent biocompatibility, and surface functionalizability. However, blue/green-emitting CDs suffer from limited tissue penetration and autofluorescence interference. Iron ions (Fe) and pyrophosphate ions (PPi) are crucial biomarkers in various biological processes, with deviations in their concentrations linked to various diseases including cancer. Therefore, the development of highly sensitive and selective sensors for Fe and PPi detection is vital. To address these challenges, we present red-emitting nickel-doped carbon dots (Ni-CDs) synthesized via a simple one-pot hydrothermal method, offering advantages for deep-tissue imaging and therapeutics.

Results: Herein, we report a one-pot hydrothermal synthesis of nickel-doped CDs (Ni-CDs) that exhibit both paramagnetic responsiveness and red fluorescence (λ/λ = 475 nm/630 nm). Using citric acid and p-phenylenediamine as raw materials, we successfully fabricated Ni-CDs with high fluorescence quantum yield of 24 % and uniform size distribution (5.13 ± 0.04 nm). The Ni-CDs serve as an "on-off-on" fluorescent sensor for simultaneous detection of Fe and PPi with low detection limits of 0.051 μM and 0.31 μM, respectively. They demonstrate high sensitivity and selectivity in detecting Fe in real water samples and PPi in human urine and blood samples. Furthermore, Ni-CDs exhibit good biocompatibility and enable real-time visualization of intracellular Fe and PPi dynamics in cancer cells. Under 808 nm laser irradiation (1.5 W/cm), Ni-CDs achieve high photothermal conversion efficiency of 59.1 % and generate cytotoxic reactive oxygen species, leading to synergistic photothermal/photodynamic cancer cell apoptosis of 98.8 %.

Significance: This "two-in-one" theranostic platform based on Ni-CDs overcomes traditional limitations of conventional blue/green-emitting CDs, offering deep-tissue compatibility and minimized background interference, and multifunctional integration. Our methodology provides a generalized design strategy for wavelength-engineered CD hybrids, enabling innovative applications in point-of-care diagnostics and precision oncology. The multifunctional properties of Ni-CDs highlight their potential to revolutionize biomedical research and clinical practice.