Strategic Assessment of Boron-Enriched Carbon Dots/Naproxen: Diagnostic, Toxicity, and In Vivo Therapeutic Evaluation.

Cancer is a significant global public health concern, ranking as the leading cause of mortality worldwide. This study thoroughly explores boron-doped carbon dots (B-CDs) through a simple/rapid microwave-assisted approach and their versatile applications in cancer therapy. The result was highly uniform particles with an average diameter of approximately 4 nm. B-CDs exhibited notable properties, including strong fluorescence with a quantum yield of 33%. Colloid stability tests revealed their robustness within a pH range of 6-12, NaCl concentrations up to 0.5 M, and temperatures ranging from 30 to 60 °C. The study also delved into the kinetics of naproxen release from B-CDs as a drug delivery system. The loading efficacy of naproxen exceeded 55.56%. Under varying pH conditions, the release of naproxen from B-CDs conformed to the Peppas-Sahlin model, demonstrating the potential of Naproxen-loaded CDs for cancer drug delivery. In vitro cytotoxicity assessments, conducted using the CCK-8 Assay and flow cytometry, consistently indicated low toxicity with average cell viability exceeding 80%. An in vivo toxicity test on female mice administered 20 mg/kg of B-CDs for 31 days revealed reversible histological changes in the liver and kidneys, while the pancreas remained unaffected. Importantly, B-CDs did not impact the mice's physical behavior, body weight, or survival. In vivo experiments targeting benzo(a)pyrene-induced fibrosarcoma demonstrated the efficacy of B-CDs as naproxen carriers in the treatment of cancer. This in vivo study provides a thorough comprehension of B-CDs synthesis and toxicity and their potential applications in cancer therapy and drug delivery systems.

Naproxen release from carbon dot coated magnetite nanohybrid as versatile theranostics for HeLa cancer cells.

Nanohybrid magnetite carbon dots (Fe3O4@CDs) were successfully synthesized to improve their applicability in multi-response bioimaging. The nanohybrid was prepared via pyrolysis and further loaded with naproxen (NAP) to promote drug delivery features. The characterization of the synthesized Fe3O4@CDs demonstrated the existence of Fe3O4 crystals by matching with JCPDS 75-0033 and its narrow size distribution at 11.30 nm; further, FTIR spectra confirmed the presence of Fe-O groups, C-O stretching, C-H sp2, and C-O bending, along with dual-active fluorescence and magnetic responses. The nanohybrids also exhibit particular properties such as a maximum wavelength of 230.5 nm, maximum emission in the 320-420 nm range, and slight superparamagnetic reduction (Fe3O4: 0.93620 emu per g; Fe3O4@CDs: 0.64784 emu per g). The cytotoxicity assessment of the nanohybrid revealed an excellent half-maximal inhibitory concentration (IC50) of 17 671.5 ± 1742.6 µg mL-1. Then, the incorporation of NAP decreased the cell viability to below 10%. The kinetic release properties of NAP are also confirmed as pH-dependent, and they follow the Korsmeyer-Peppas kinetics model. These results indicated that the proposed Fe3O4@CDs can be used as a new model for theranostic treatment.

Comparison Direct Synthesis of Hyaluronic Acid-Based Carbon Nanodots as Dual Active Targeting and Imaging of HeLa Cancer Cells.

The present study explores the potential of carbon nanodots (CDs) synthesized from hyaluronic acid using microwave-assisted and furnace-assisted methods as bioimaging agents for cancer cells. The investigation on the effect of microwave-assisted and furnace-assisted times (2 min and 2 h) on determining CD character is dominantly discussed. Various CDs, such as HA-P1 and HA-P2 were, respectively, synthesized through the furnace-assisted method at 270 °C for 2 min and 2 h, whereas HA-M1 and HA-M2 were synthesized with the microwave-assisted method for 2 min and 2 h, respectively. Overall, various CDs were produced with an average diameter, with the maximum absorption of HA-P1, HA-P2, HA-M1, and HA-M2 at 234, 238, 221, and 217 nm, respectively. The photoluminescence spectra of these CDs showed particular emissions at 320 nm and excitation wavelengths from 340 to 400 nm. Several characterizations such as X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, X-ray diffraction, and Raman spectroscopy reveal the CD properties such as amorphous structures, existence of D bands and G bands, and hydrophilic property supported with hydroxyl and carboxyl groups. The quantum yields of HA-M1, HA-M2, HA-P1, and HA-P2 were 12, 7, 9, and 23%, respectively. The cytotoxicity and in vitro activity were verified by a cell counting kit-8 assay and confocal laser scanning microscopy, which show a low toxicity with the percentage of living cells above 80%.

Naproxen release aspect from boron-doped carbon nanodots as a bifunctional agent in cancer therapy.

In this present study, boron-carbon nanodots were synthesized by the hydrothermal method. Boron-carbon nanodots were prepared by varying the concentration ratios of boronic acid and citric acid: 1 : 25, 2 : 1, and 25 : 1, respectively. The precursors were then poured into a Teflon autoclave and heated at 240° for 4 h. This research aims to synthesise and evaluate the potential of boron-carbon nanodots as a bioimaging agent and naproxen delivery carrier. An X-ray diffractogram showed that the boron-carbon nanodots were amorphous. To analyse the functional groups, FTIR and XPS analysis was carried out. Spectrofluorometric analysis (λ ex 320 nm) showed that the formulation of boron-carbon nanodots 2 : 1 (BCD 2 : 1) has the most ideal fluorescent properties at λ em 453 nm, whereas UV-vis analysis showed λ max at 223 nm, with a quantum yield of 52.29%. A confocal laser scanning micrograph and toxicity test (MTT assays) showed that boron-carbon nanodots delivered naproxen efficiently with loading amount and loading efficiency of naproxen 28% and 65%, respectively. Furthermore, it induced an anticancer effect in HeLa cells. This result indicated that boron-carbon nanodots can be used as a bioimaging agent and naproxen delivery carrier.

Comparison of the effects of synthesis methods of B, N, S, and P-doped carbon dots with high photoluminescence properties on HeLa tumor cells.

Although heteroatom doping is widely used to promote the optical properties of carbon dots for biological applications, the synthesis process still has problems such as multi-step process, complicating the setting of instrument along with uncontrolled products. In the present study, some elements such as boron, nitrogen, sulfur, and phosphor were intentionally doped into citric acid-based carbon dots by furnace- and microwave-assisted direct and simple carbonization processes. The process produced nanoparticles with an average diameter of 5-9 nm with heteroatoms (B, N, S, and P) placed on the core and surface of carbon dots. Among the doped carbon dots prepared, boron-doped carbon dots obtained by the microwave-assisted (B-CDs2) process showed the highest photoluminescence intensity with a quantum yield (QY) of about 32.96%. All obtained carbon dots exhibit good stability (at pH 6-12 and high ionic strength concentrations up to 0.5 M), whereas cytotoxicity analysis showed that all doped carbon dots are low-toxic with an average cell viability percentage above 80% up to 500 µg mL-1. It can be observed from the CLSM image of all doped carbon dots that the doping process not only increases the QY percentage, but also might accelerate the HeLa uptake on it and produce strong carbon dot emission at the cytoplasm of the cell. Thus, the proposed synthesis process is promising for high-potency bioimaging of HeLa cancer cells.