Development and application of naturally derived, cost-effective CQDs with cancer targeting potential.

Carbon quantum dots (CQDs) derived from natural sources have obtained potential interest in biomedical imaging and therapy because of their excellent biocompatibility properties, which include water solubility, simple synthesis and low cytotoxicity. Here the cytotoxicity of ethylene-diamine doped carbon quantum dots (N-CQDs) delivered to breast cancer MCF-7 cells was investigated. Folic acid was used to raise folate recognition and increase FA-NCQD accumulation in the cells, then apoptosis was assayed using nuclear fragmentation, acridine orange labeling, fluorescence imaging, flow cytometry, and caspase 3 expression. The data show that functionalization of these CQDs, derived from a natural source, have potential application in eliminating cancer cells, as shown here for the invasive breast cancer cells, MCF-7. This nano-delivery system provides a novel target therapy possibility therapeutic approach for cancer cells.

Fighting Non-Small Lung Cancer Cells Using Optimal Functionalization of Targeted Carbon Quantum Dots Derived from Natural Sources Might Provide Potential Therapeutic and Cancer Bio Image Strategies.

Non-small cell lung cancer (NSCLC) is an important sub-type of lung cancer associated with poor diagnosis and therapy. Innovative multi-functional systems are urgently needed to overcome the invasiveness of NSCLC. Carbon quantum dots (CQDs) derived from natural sources have received interest for their potential in medical bio-imaging due to their unique properties, which are characterized by their water solubility, biocompatibility, simple synthesis, and low cytotoxicity. In the current study, ethylene-diamine doped CQDs enhanced their cytotoxicity (98 ± 0.4%, 97 ± 0.38%, 95.8 ± 0.15%, 86 ± 0.15%, 12.5 ± 0.14%) compared to CQDs alone (99 ± 0.2%, 98 ± 1.7%, 96 ± 0.8%, 93 ± 0.38%, 91 ± 1.3%) at serial concentrations (0.1, 1, 10, 100, 1000 µg/mL). In order to increase their location in a specific tumor site, folic acid was used to raise their functional folate recognition. The apoptotic feature of A549 lung cells exposed to N-CQDs and FA-NCQDs was characterized by a light orange-red color under fluorescence microscopy. Additionally, much nuclear fragmentation and condensation were seen. Flow cytometry results showed that the percentage of cells in late apoptosis and necrosis increased significantly in treated cells to (19.7 ± 0.03%), (27.6 ± 0.06%) compared to untreated cells (4.6 ± 0.02%), (3.5 ± 0.02%), respectively. Additionally, cell cycle arrest showed a strong reduction in cell numbers in the S phase (14 ± 0.9%) compared to untreated cells (29 ± 0.5%). Caspase-3 levels were increased significantly in A549 exposed to N-CQDs (2.67 ± 0.2 ng/mL) and FA-NCQDs (3.43 ± 0.05 ng/mL) compared to untreated cells (0.34 ± 0.04 ng/mL). The functionalization of CQDs derived from natural sources has proven their potential application to fight off non-small lung cancer.

The Effect of Encapsulated Apigenin Nanoparticles on HePG-2 Cells through Regulation of P53.

Apigenin (Ap) is one of the most important natural flavonoids that has potent anticancer activity. This study was designed, for the first time, to load Ap into chitosan to improve its hydrophobicity and then it was coated with albumin-folic acid to increase its stability and bioavailability and to target cancer cells. The newly developed encapsulated Ap (Ap-CH-BSA-FANPs) was characterized and tested in vitro. The zeta potential of -17.0 mV was within the recommended range (-30 mV to +30 mV), indicating that encapsulated apigenin would not quickly settle and would be suspended. The in vitro results proved the great anticancer activity of the encapsulated apigenin on HePG-2 cells compared to pure Ap. The treated HePG-2 cells with Ap-CH-BSA-FANPs demonstrated the induction of apoptosis by increasing p53 gene expression, arresting the cell cycle, increasing caspase-9 levels, and decreasing both the MMP9 gene and Bcl-2 protein expression levels. Moreover, the higher antioxidant activity of the encapsulated apigenin treatment was evident through increasing SOD levels and decreasing the CAT concentration. In conclusion, the Ap-CH-BSA-FANPs were easy to produce with low coast, continued drug release, good loading capacity, high solubility in physiological pH, and were more stable than the formerly Ap-loaded liposomes or PLGA. Moreover, Ap-CH-BSA-FANPs may be a promising chemotherapeutic agent in the treatment of HCC.

Silymarin/curcumin loaded albumin nanoparticles coated by chitosan as muco-inhalable delivery system observing anti-inflammatory and anti COVID-19 characterizations in oleic acid triggered lung injury and in vitro COVID-19 experiment.

Respiratory infected by COVID-19 represents a major global health problem at moment even after recovery from virus corona. Since, the lung lesions for infected patients are still sufferings from acute respiratory distress syndrome including alveolar septal edema, pneumonia, hyperplasia, and hyaline membranes Therefore, there is an urgent need to identify additional candidates having ability to overcome inflammatory process and can enhance efficacy in the treatment of COVID-19. The polypenolic extracts were integrated into moeties of bovine serum albumin (BSA) and then were coated by chitosan as a mucoadhesion polymer. The results of interleukin-6, and c-reactive protein showed significant reduction in group treated by Encap. SIL + CUR (64 ± 0.8 Pg/µL & 6 ± 0.5 µg/µL) compared to group treated by Cham. + CUR (102 ± 0.8 Pg/µL & 7 ± 0.5 µg/µL) respectively and free capsules (with no any drug inside) (148 ± 0.6 Pg/µL & 10 ± 0.6 µg/µL) respectively. Histopathology profile was improved completely. Additionally, encapsulating silymarin showed anti-viral activity in vitro COVID-19 experiment. It can be summarized that muco-inhalable delivery system (MIDS) loaded by silymarin can be used to overcome inflammation induced by oleic acid and to overcome COVID-19.

Photoactive electrospun cellulose acetate/polyethylene oxide/methylene blue and trilayered cellulose acetate/polyethylene oxide/silk fibroin/ciprofloxacin nanofibers for chronic wound healing.

This study aimed to synthesize cellulose acetate (CA)-based electrospun nanofibers as drug delivery dressings for chronic wound healing. For the first time, CA was blended with polyethylene oxide (PEO) using acetone and formic acid. Methylene blue (MB) was incorporated into monolayered random CA/PEO nanofibers. They had a diameter of 400-600 nm, were hydrophilic, and generated reactive oxygen species upon irradiation. Thus, they mediated antimicrobial photodynamic inactivation (aPDI) against isolated biofilm-forming Staphylococcus aureus, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Bacterial survival, biofilm mass, and produced pyocyanin of the treated groups declined by 90%, 80%, and 3 folds, respectively. On the other hand, ciprofloxacin (Cipro) was loaded into an innovative trilayered aligned nanofiber consisting of CA/PEO surrounding a blank layer of silk fibroin. Cipro and MB release followed the Korsmeyer-Peppas model. An infected diabetic wound mouse model was established and treated with either MB-aPDI or Cipro. A combined therapy group of MB-aPDI followed by Cipro was included. The combined therapy showed significantly better results than monotherapies delineated by elevation in re-epithelization, collagen deposition, CD34, and TGF-ß expression, along with a decline in CD95+ cells. This study deduced that drug-loaded CA electrospun nanofibers might be exploited in multimodal chronic wound healing.

Sandwich nanohybrid of chitosan-polyvinyl alcohol for water treatment and Sofosbuvir drug delivery for anti-hepatitis C virus (HCV).

The incorporation between nano-polyvinyl alcohol (PVA) and nano-chitosan (Cs) to produce sandwich nanohybrid (SNH) for water treatment and improvement the adsorption of sofosbuvir drug (SOF). The photocatalytic activity and formation of reactive oxygen species (ROS) were detected with oxidation of organic dyes such as Rhodamine B (RhB), methylene blue (MB), and methyl orange (MO). The effect of SNH on the release of SOF in blood and inside the cells at pH 7.4 and pH 6.8, respectively were observed by UV-Visible spectroscopy (UV-Vis). The binding constant (Kb) was reported at 0.0035 min-1 and the loading constant at 0.0024 min-1, while the release efficiency was 42.6% at pH 7.4 and 74.7% at pH 6.8. The efficiency of photocatalytic activity against organic dyes MO, MB, and RhB are detected at 2.4% and 1%, and 42%, respectively. The cytotoxicity of SNH has been observed with MDA-MB-231 and HepG2 cell line with three concentrations of SNH, where the little concentration has low effect on the HepG2 and high viability, this result was reversed with the high concentration, also the yellow color due to the lysis of the cells. The antioxidant of the SNH was detected by FRAP technique.

Spectroscopic study of self-assembly of anti-hepatitis C virus sofosbuvir drug with bio-polymeric nanoparticles for improving the drug release effect.

Self-assembly of Sofosbuvir drug (SOF) anti-hepatitis C virus (HCV) with bio-polymeric nanoparticles such as chitosan nanoparticles (Cs NPs) and polyvinyl alcohol nanoparticles (PVA NPs), the novel composites have been characterized successfully by different analysis such as Energy-dispersive X-ray spectroscopy (EDX), Scanning electron microscopy (SEM), UV-Visible spectrophotometer (UV-Vis) and Fourier Transmittance Infrared (FT-IR). The improvement of the Sofosbuvir effect as a result of loading drug on the bio-polymer NPs surface has been detected by the UV-Vis, and fluorescence spectroscopy techniques. The improvement of SOF efficiency was revealed via studying the drug release of SOF from biopolymers NPs surface at pH 7.4, UV-Vis spectra used for the releasing process. The binding constant (Kb) value was reported at 0.000055 and 0.3613 min-1 for Cs and PVA NPs respectively. Also, the value of KSV was documented at 0.0014 and 7.16 min-1 for Cs@SOF and PVA@SOF hybrid nanocomposite. The incorporation rate (k) of SOF on the surface of biopolymer nano molecules was calculated to be 0.00812 and 0.0165 min-1 for Cs and PVA NPs, respectively. Besides the observed value of (n) was close to the unit 0.74 and 0.86 for Cs and PVA NPs, respectively. The SOF released from Cs NPs surface was documented at 0.09 mg after 24 h, while PVA NPs reported at 0.7 mg at the same time and the release efficiency is 56.5 and 73% for Cs@SOF and PVP@SOF, respectively. From the results, we suggest Cs/SOF and PVA/SOF hybrid nanocomposites have spectroscopic results that make them promising candidate drugs, but need to the clinical trials.

Extraction of chlorophyll and carotenoids loaded into chitosan as potential targeted therapy and bio imaging agents for breast carcinoma.

In the current study, the treatment efficacy of ECHCAH was evaluated in vitro studies using cell viability and flow cytometry in human TNBCs. The results here showed significant gradual reduction in growth of TNBCs (MDA-231cell lines) after their exposure to serial concentrations for hydrogel assembly (5 µg/mL to 25 µg/mL) for 24 and 48 h, representing (86 ± 1% to 45 ± 1.5% p < 0.001) and (79 ± 1.5% to 35 ± 2.5% p < 0.001) respectively. The flow cytometry showed significant increase in the present of late apoptotic and necrotic cells (64% ± 1.2 and 27% ± 0.3 p < 0.001) after 48 h incubation compared to untreated cells (1.13% ± 0.3 and 4% ± 0.2 p < 0.001) respectively. It can be summarized that ECHCA inside targeted hydrogel assemblies can inhibit proliferation of cancer cells.

Cancer antigen 125 assessment using carbon quantum dots for optical biosensing for the early diagnosis of ovarian cancer.

Fluorometric quantification of biological molecules is a key feature used in many biosensing studies. Fluorescence resonance energy transfer (FRET) using highly fluorescent quantum dots offers highly sensitive detection of the in-proximity wide variety of analyst molecules. In this contribution, we report the use of carbon quantum dots (CDs) for the ultrasensitive optical biosensing of cancer antigen 125 (CA-125) in the early malignant stage. This approach is based on monitoring the quenching of CDs luminescence at 535 nm by CA-125 after excitation at 425 nm and pH 10. The calibration of this method was performed in the concentration range of CA-125 from 0.01 to 129 U ml-1 (R 2 = 0.99) with a detection limit of 0.66 U ml-1, which matches remarkably with the standard chemiluminometric method in control and real patient samples. The sensing mechanism for cancer antigen 125 assessment was discussed on the basis of fluorescence quenching of CDs and time-resolved photoluminescence spectroscopy. The current method is easy, sensitive, cost-effective and provides a wide range of validity, which helps in overcoming the limitations of high cost and time consumption exhibited by many other traditional clinical assays for CA-125 quantification.

Highly Selective Optical Sensor Eu (TTA)3 Phen Embedded in Poly Methylmethacrylate for Assessment of Total Prostate Specific Antigen Tumor Marker in Male Serum Suffering Prostate Diseases.

A low-cost, simple, and highly selective method was used for the assessment of total prostate specific antigen (tPSA) in the serum of prostate cancer patients. This method is based on quenching the intensity of luminescence displayed by the optical sensor Eu (TTA)3 phen/poly methylmethacrylate (PMMA) thin membrane or film upon adding different concentrations of tPSA. The luminescent optical sensor was synthesized and characterized through absorption, emission, scanning electron microscopy (SEM), and x-ray diffraction (XRD), and is tailored to present red luminescence at 614 nm upon excitation at 395 nm in water. The fabricated sensor fluorescence intensity is quenched in the presence of tPSA in aqueous media. The fluorescence resonance energy transfer (FRET) is the main mechanism by which the sensor performs. The sensor was successfully utilized to estimate tPSA in the serum of patients suffering prostate cancer in a time and cost effective way. The statistical results of the method were satisfactory with 0.0469 ng mL-1 as a detection limit and 0.99 as a correlation coefficient.

Highly Efficient Gold Nano-Flower Optical Biosensor Doped in a Sol-Gel/PEG Matrix for the Determination of a Calcitonin Biomarker in Different Serum Samples.

We developed a novel, simple, sensitive, accurate, and precise method for the determination of calcitonin in different serum samples with medullar thyroid carcinoma. The designed flower-like thin film gold nanoparticles doped in a sol-gel/polyethylene glycol mold are used as an optical biosensor for the efficient determination of calcitonin. The sensor was characterized by transmission electron microscopy, scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray microanalysis, and Fourier-transform infrared spectroscopy. The efficiency of the considered bio-sensor is done using the quencher calcitonin of the emission band at 360 nm of biomarker obtained at λex = 333 nm in acetonitrile solvent. The sensing mechanism was based on fluorescence resonance energy transfer. The remarkable quenching of the fluorescence intensity at 360 nm of optical sensor by various concentrations of calcitonin was successfully used as an optical biosensor for the assessment of calcitonin for different serum samples of patients with medullar thyroid carcinoma. The calibration plot was prepared for the concentration range 0.01-1000 pg/mL of calcitonin with a correlation coefficient of 0.99 and a detection limit of 0.707 pg/mL. The suggested method augments the sensitivity of calcitonin as a useful biomarker for the early diagnosis of medullar thyroid carcinoma. This method is considered as a gateway for the construction of a new prototype for the follow-up of thyroid cancer in the spinal cord during and after treatment.

Global and distribution analysis of fluorescence decays and spectrofluorimetric determination of stoichiometry and association constant of the inclusion complex of 2-amino-5,6-dimethyl-benzimidazole with beta-cyclodextrin.

The steady state and time-resolved fluorescence study of 2-amino-5,6-dimethyl-benzimidazole (ADBI) have been studied in aqueous solution of beta-cyclodextrin (beta-CD). The fluorescence decays were analyzed by global analysis and distribution analysis in order to get insight about the inclusion process. The fluorescence lifetime of ADBI is increased in beta-CD and an enhancement of the emission, is observed, together with negligible changes in the energy of ADBI in beta-CD. The experimental data show that beta-CD reacts with ADBI to form a 1:1 host-guest complex with association constant was determined to be 2074+/-77M(-1). Both global analysis and distribution analysis of the fluorescence decays support the formation of only 1:1 inclusion complex. AM1 calculation shows that the size of ADBI was appropriate for good insertion within the beta-CD cavity and the inclusion of ADBI inside the beta-CD cavity should takes place from the side of the amino group substituent.

New approach for evaluation optical absorption measurements of charge transfer complexes between dimethoxynaphthalenes and tetracyanoethylene: singular value decomposition method.

Singular-value decomposition (SVD) method is a numerical multidimensional technique appropriate for evaluation of optical absorption measurements of 1:1 charge transfer complexes (CTCs). Matrix algebra of the absorption data for different solutions and wavenumbers is primarily used for evaluation of the equilibrium constant and to obtain some general expressions to illustrate physical significance of the results obtained. The influence of the ratio of the concentrations of donor and acceptor is examined. It can lead to information about the stoichiometry of the complex formed in solution. Calculations on data for CTCs between dimethoxynaphthalene (DMNs) and tetracyanoethylene (TCNE) in CH2Cl2 at various temperatures are described. The results suggest that there is a noticeable difference in the K4, caused by substitutions at alpha- and beta-positions, because the alpha-position of naphthalene exhibits relatively high electron density compared with the corresponding beta-position. There is a linear correlation between the donor HOMO energy and charge-transfer absorption maxima.