Photothermal performance of a novel carbon dot and its conjugate with disulfiram for prostate cancer PC3 cell therapy.

Aim: To develop and employ a copper, sulfur, nitrogen-carbon quantum dot (C,S,N-CQD) multifunctional platform for synergistic cancer therapy, combining chemotherapy and photothermal treatment with in vitro cancer cell imaging. Materials & methods: Cu,S,N-CQDs were synthesized hydrothermally, loaded with disulfiram (DSF), and characterized through UV-Vis spectrophotometry, photoluminescence, Fourier-transform infrared spectroscopy, high-resolution transmission electron microscopy, dynamic light scattering, x-ray diffraction and EDAX. Results: Cu,S,N-CQD exhibited 5.5% absolute fluorescence quantum yield, 46.0% photothermal conversion efficiency and excellent stability. The release of DSF-loaded Cu,S,N-CQD, photothermal performance, and IC50 on PC3 prostate cancer cells, were evaluated. The impact of cellular glutathione on nanocarrier performance was investigated. Conclusion: Cu,S,N-CQD as a photothermal agent and DSF carrier showed synergy (combination index: 0.71) between chemotherapy and photothermal therapy. The nanocarrier simultaneously employed for in vitro cancer cell imaging due to its unique fluorescence properties.

Nanometer-scale particles can be used to treat and detect cancer in many ways. A type of nanoparticle was designed to attack cancer in two different ways. These nanoparticles ­ copper, sulfur, nitrogen­carbon quantum dots (C,S,N­CQDs) ­ were designed to both deliver a chemotherapy drug to cancer cells and act as a photothermal agent. This means that when light of a particular energy is shone on these particles, they heat up and can kill cancer cells. These C,S,N­CQDs loaded with the chemotherapy drug disulfiram were then tested on the prostate cancer cell line PC3. When a laser was shone on these particles and they became excited, they reduced cancer cell viability both by releasing the drug and heating up and killing the surrounding cells. These Cu,S,N-CQDs are also fluorescent, meaning they can be used to image cancer cells in tests like these.

Ultrasensitive FRET-based aptasensor for interleukin-6 as a biomarker for COVID-19 progression using nitrogen-doped carbon quantum dots and gold nanoparticles.

A label-free and specific FRET-based interleukin-6 (IL-6) aptasensor was developed using a DNA aptamer modified with nitrogen-doped carbon quantum dots (NCDs) and gold nanoparticles (AuNPs) as a donor-quencher pair. The assayed target was capable of disrupting the donor-acceptor assemblies yielding a concentration-related fluorescence recovery of NCDs (λem = 445 nm and λex = 350 nm). By designing two different probes, the interaction of DNA aptamers with IL-6 protein was studied using FRET efficiency. It appeared that the sensing probes showed slightly different sensing profiles. One of the aptasensors showed a linear response of 1.5-5.9 pg/mL for IL-6 with a coefficient of determination of R2 ≥ 0.99 and the a detection limit of 0.82 pg/mL (at S/N = 3). The experimental results indicated that the biosensor can be applied to determine IL-6 in human serum (with recovery of 95.7-102.9%). Due to the high sensitivity, excellent selectivity, and simplicity of the procedure, this strategy represents a promising alternative for IL-6 sensing in clinical applications.

Carbon quantum dots-Annexin V probe: photoinduced electron transfer mechanism, phosphatidylserine detection, and apoptotic cell imaging.

An annexin V-based probe is designed and fabricated using carbon quantum dot as highly stable and biocompatible fluorescent crystals for real-time fluorescence imaging of apoptotic cells. Carbon quantum dots were synthesized, characterized, and conjugated to annexin V. The fluorescence of CQDs at 450 nm (excitation at 350 nm) is quenched due to the photoinduced electron transfer between "carbon quantum dots" and two amino acids (tyrosine and tryptophan) in the annexin structure as quencher. The probe shows very strong and bright fluorescence emission in the presence of phosphatidylserine on the outer layer of the apoptotic cell membrane. It was shown that using fluorescence spectroscopy, the probe can be applied to sensitive phosphatidylserine determination and using fluorescence microscopy, it is possible to monitor cell apoptosis in real time.

Hairpin oligosensor using SiQDs: Förster resonance energy transfer study and application for miRNA-21 detection.

MicroRNAs are known to be tumor suppressors and promoters and can be used as cancer markers. In this work, a novel oligosensor was designed using Si quantum dots (SiQDs) for the detection of miRNAs. Five-nanometer SiQDs were synthesized, with a band gap of 2.8 eV, fluorescence lifetime of 4.56 µs (τ1/2 = 3.26 µs), quantum yield of 25%, fluorescence rate constant of 6.25 × 104, and non-radiative rate constant of 1.60 × 105 s-1. They showed excellent water dispersibility, good stability (with 95% confidence for 6-month storage) without photobleaching, and high biocompatibility, with an IC50 value of 292.2 µg/L. The SiQDs and Black Hole Quencher-1 (BHQ1) were conjugated to the 5' and 3' terminals of an oligomer, respectively. The resulting hairpin molecular beacon showed resonance energy transfer efficiency of 63%. A distance of 0.91 R (Förster distance) between SiQD and BHQ1 was obtained. In the presence of a stoichiometric amount of the complementary oligonucleotide (ΔGhybridization = -35.09 kcal mol-1), 98% of the fluorescence was recovered due to loop opening of the hairpin structure. The probe showed good selectivity toward miRNA-21, with a limit of detection of 14.9 fM. The oligosensor recoveries of miRNA-21 spiked in human serum and urine were 94-98% and 93-108%, respectively.

Label-free triplex DNA-based biosensing of transcription factor using fluorescence resonance energy transfer between N-doped carbon dot and gold nanoparticle.

Herein, a new turn-on fluorescent assay was established as a platform for the sensing of transcription factor NF-kB p50 based on triplex DNA labeled with N-doped carbon dots (NCDs) and gold nanoparticles (AuNPs) as donors and acceptors, respectively in the fluorescence resonance energy transfer (FRET) system. The synthetized nanoparticles were studied by different characterization techniques. A labeled DNA molecule was designed to form a triplex when no target protein existence and reported its formation by the change in FRET efficiency. While the triplex DNA was formed, the fluorescence of carbon dots at 503 nm (excitation at 460 nm) was quenched by FRET between NCD and AuNP. However, presence of NF-kB p50 followed by the considerable enhancement in the fluorescence intensity caused by the release of AuNPs labeled single stranded DNA from the triplex DNA structure, used for sensitive determination of the transcription factor. This technique showed a linearity (R2 = 0.9943) in the range of 20-150 pM with a limit of detection of 9 pM for the determination of NF-kB p50. Moreover, the sequence-specific triplex-based biosensor could discriminate NF-kB p50 from the other proteins with high selectively. Our results suggest that the biosensor provides a generalizable platform for rapid detection of NF-kB p50 in synthetic medium, promising in prevention and early diagnosis of cancer.

Synthesis of folic acid conjugated photoluminescent carbon quantum dots with ultrahigh quantum yield for targeted cancer cell fluorescence imaging.

Folic acid functionalized carbon quantum dots (FA-CQDs) with ultrahigh quantum yield (50 %) were synthesized by one-pot hydrothermal route using citric acid. The synthesized CQDs were characterized by fluorescence spectroscopy, transmission electron microscopy (TEM), dynamic light scattering (DLS) and X-ray diffraction. The cell viability of about 95 % and 97 % were obtained for MTT assay of the CQDs and FA-CQDs toward MCF-7 cells after 24 h of incubation respectively. The FA-CQDs were successfully applied for targeted imaging of ovarian cancer (type HeLa) and human breast adenocarcinoma (type MCF7) cells using fluorescence microscope.

Micro-RNA detection based on fluorescence resonance energy transfer of DNA-carbon quantum dots probes.

Carbon quantum dots have been proposed as an effective platform for miRNA detection. Carbon dots were synthesized by citric acid. The synthesized dots were characterized by dynamic light scattering, UV-Vis spectrophotometry, spectrofluorimetry, transmission electron microscopy and FT-IR spectrophotometry. The fluorescence quantum yield of the synthesized dots was determined using quinine sulfate as the standard. The FAM-labeled single stranded DNA, as sensing element, was adsorbed on dots by π-π interaction. The quenching of the dots fluorescence due to fluorescence resonance energy transfer (FRET) was used for mir 9-1 detection. In the presence of the complementary miRNA, the FRET did not take place and the fluorescence was recovered.