Synthesis of chitosan polyethylene glycol antibody complex for delivery of Imatinib in lung cancer cell lines.

Lung cancer is known as the most common cancer. Although the Ramucirumab antibody is a second-line treatment for lung cancer, the high interstitial fluid pressure limits the antibody's performance. In this way, Imatinib is a chemotherapeutic drug to reduce the interstitial fluid pressure. Up to now, unfortunately, both Ramucirumab and imatinib have not been reported in one nanosystem for cancer therapy. To fulfill this shortcoming, this paper aims to design a chitosan nanocarrier that loads imatinib and attaches to Ramucirumab for selective bonding to A549. Therefore, this paper aims to develop a polymeric nanosystem for non-small cell lung cancer (NSCLC) treatment. In first, the chitosan polyethylene glycol nanoparticle is synthesized, loaded with imatinib, and then targeted using Ramucirumab. Afterwards, the CS-PEG-Ab-Im by FTIR, TEM, DLS, zeta potential, and TGA techniques are characterized. The size of CS-PEG-Ab-Im was 25-30 nm, its surface charge was 13.1 mV, and the shape of CS-PEG-Ab-Im was nearly spherical and cylindrical. The therapeutic potential of CS-PEG-Ab-Im was assessed using the A549 cell line. According to the obtained results, the cell viability was 48% after 48 h of treatment of A549 cells using the IC50 concentration of CS-PEG-Ab-Im (100 nanomolar). Moreover, the apoptosis and cell cycle arrest percentages were increased by 3 and 6 times, respectively, as compared to free imatinib. Furthermore, the release rate of imatinib from CS-PEG-Ab-Im in an acidic medium was 17% during 1 h, indicating five times the imatinib release in the natural medium. Eventually, the result of flow cytometry indicates the more apoptotic effect of nanosystem to free imatinib and CS-PEG-Ab. Besides, cell arresting result exhibits the CS-PEG-Ab-Im and causes cell arrested at G1 by %8.17. Thus, it can be concluded that CS-PEG-Ab-Im can be an ideal nanosystem in NSCLC treatment.

Targeted Anticancer Drug Delivery Using Chitosan, Carbon Quantum Dots, and Aptamers to Deliver Ganoderic Acid and 5-Fluorouracil.

Breast cancer is a malignancy that affects mostly females and is among the most lethal types of cancer. The ligand-functionalized nanoparticles used in the nano-drug delivery system offer enormous potential for cancer treatments. This work devised a promising approach to increase drug loading efficacy and produce sustained release of 5-fluorouracil (5-FU) and Ganoderic acid (GA) as model drugs for breast cancer. Chitosan, aptamer, and carbon quantum dot (CS/Apt/COQ) hydrogels were initially synthesized as a pH-sensitive and biocompatible delivery system. Then, CS/Apt/COQ NPs loaded with 5-FU-GA were made using the W/O/W emulsification method. FT-IR, XRD, DLS, zeta potentiometer, and SEM were used to analyze NP's chemical structure, particle size, and shape. Cell viability was measured using MTT assays in vitro using the MCF-7 cell lines. Real-time PCR measured cell apoptotic gene expression. XRD and FT-IR investigations validated nanocarrier production and revealed their crystalline structure and molecular interactions. DLS showed that nanocarriers include NPs with an average size of 250.6 nm and PDI of 0.057. SEM showed their spherical form, and zeta potential studies showed an average surface charge of +37.8 mV. pH 5.4 had a highly effective and prolonged drug release profile, releasing virtually all 5-FU and GA in 48 h. Entrapment efficiency percentages for 5-FU and GA were 84.7±5.2 and 80.2 %±2.3, respectively. The 5-FU-GA-CS-CQD-Apt group induced the highest cell death, with just 57.9 % of the MCF-7 cells surviving following treatment. 5-FU and GA in CS-CQD-Apt enhanced apoptotic induction by flow cytometry. 5-FU-GA-CS-CQD-Apt also elevated Caspase 9 and downregulated Bcl2. Accordingly, the produced NPs may serve as pH-sensitive nano vehicles for the controlled release of 5-FU and GA in treating breast cancer.

Betanin alleviates oxidative stress through the Nrf2 signaling pathway in the liver of STZ-induced diabetic rats.

BACKGROUND: Continuing hyperglycemia causes and exacerbate oxidative stress. Betanin as the principal pigment of red beet root has antioxidant, anti-inflammatory, and anti-diabetic properties. The purpose of this study was to investigate the potency of betanin on antioxidant defense in STZ-induced diabetic rats' livers. METHODS: STZ at a single dose of 60 mg/kg body weight was intraperitoneally injected and betanin (10, 20, and 40 mg/kg/day) was administered orally for 28 days. Malondialdehyde (MDA), total antioxidant capacity (TAC), protein carbonyl (PC) levels, and the enzyme activity of superoxide dismutase (SOD), catalases and glutathione peroxidases (GPx) were evaluated in the liver. Furthermore, gene expression of Nrf2 and mentioned antioxidant enzymes were measured by Real-time PCR. RESULTS: Betanin (10 and 20 mg/kg) significantly reduced PC levels and increased antioxidant enzyme activity in diabetic rats compared to the control diabetic group (P < 0.01). In comparison to the diabetic control group, all studied genes expression in diabetic rats were increased significantly with betanin at doses of 10 and 20 mg/kg (P < 0.02). The increase in gene expression at 20 mg/kg of betanin was significantly stronger than others (P < 0.015) except for the catalase (P = 0.201), that was almost the same. Moreover, treatment of diabetic rats with 20 mg/kg of betanin could significantly increase TAC levels (P < 0.05) and decrease MDA levels (P < 0.001) compared to diabetic control group. CONCLUSIONS: Betanin could increase the antioxidant capacity of liver tissue associated with the Nrf2-mediated pathway in a dose-dependent manner.

A new colorimetric assay for sensitive detection of glucose-6-phosphate dehydrogenase deficiency based on silver nanoparticles.

Glucose-6-phosphate dehydrogenase (G6PD) is the principal enzyme in the pentose phosphate pathway that plays a fundamental role in the production of nicotinamide adenine dinucleotide phosphate, which is very important in preventing the oxidation of cells, especially red blood cells. This enzyme deficiency was associated with many disorders, the most common of which were hemolysis episodes. In the last decade, nanoparticles have been used to design optical and electronic sensors due to their unique properties. This report presents a new colorimetric method that used silver nanoparticles to detect glucose 6-phosphate dehydrogenase activity directly. The glucose-6-phosphate dehydrogenase detection mechanism was based on an aggregation of silver nanoparticles, leading to increased nanoparticle size, which causes discoloration. In the presence of the enzyme, the color of the solution was yellow, and when the enzyme was not present, the color of the solution was grayish. Utilizing this method, colorimetric sensing of glucose 6-phosphate dehydrogenase was gained with a detection limit of 0.009 U ml-1and a linear range of 0-16.0 U ml-1. In this way, the presence or absence of the enzyme can be easily detected with the naked eye during one step.

Preparation, quality control, and biodistribution assessment of [111 In]In-DOTA-PR81 in BALB/c mice bearing breast tumors.

In this study, [111 In]In-DOTA-PR81 was developed, and its preliminary preclinical qualifications were assessed for single photon emission computed tomography (SPECT) imaging of breast cancer. DOTA-NHS-ester was practiced and successively purified by molecular filtration. The chelate:mAb ratio was determined by spectrophotometry. DOTA-PR81 was radiolabeled with In-111 and its radiochemical yield, in vitro stability, in vitro internalization, and immunoreactivity tests were performed. SPECT imaging and tissue counting were applied to evaluate the tissue distribution of [111 In]In-DOTA-hIgG and [111 In]In-DOTA-PR81 in BALB/c mice bearing breast tumors. The radiochemical yield of [111 In]In-DOTA-PR81 complex was >95.0 ± 0.5% (ITLC), and the specific activity was 170 ± 44 MBq/mg. Conjugation reaction resulted in the average number of chelators attached to a mAb (c/a) of 3.4 ± 0.3:1. The radioimmunoconjugate showed immunoreactivity towards MCF7 cell line and MUC1 antigen while its significant in vitro and in vivo stability were investigated over 48 h, respectively (93.0 ± 1.2% in phosphate-buffered saline (PBS) and 84.0 ± 1.3% in human serum). The peak concentration of internalized activity of [111 In]In-DOTA-PR81 was between 4 to 6 h. In comparison with control probes, the complex was accumulated with high specificity and sensitivity at the tumor site. Achieved results indicated that [111 In]In-DOTA-PR81 could be contemplated as an appropriate radiotracer for prognostic imaging of antigens in oncology.

Breast Tumor Targeting with PAMAM-PEG-5FU-99mTc As a New Therapeutic Nanocomplex: In In-vitro and In-vivo studies.

Dendrimer-based targeted drug delivery, as an innovative polymeric drug-delivery system, is promising for cancer therapy. Folate receptors (FR) are overexpressed in many types of tumor cells, such as breast cell carcinomas, which allow folate-targeted delivery. Therefor polyethylene glycol (PEG) modified-PAMAM G4 dendrimers were functionalized with folic acid (FA), as targeting agent. Then, 5-FU (5-fluorouracil) and 99mTc (technetium-99 m) as therapeutic agents were respectively loaded and conjugated to previous nano-complex (PEG-PAMAM G4-FA-5FU-99mTc). The value of drug loading was calculated by TGA analysis (16.97%). Drug release profiles of PEG-PAMAM G4-FA-5FU-99mTc and PEG-PAMAM G4-FA-5FU were evaluated. The radiochemical purity of PEG-PAMAM G4-FA-5FU-99mTc and PEG-PAMAM G4-FA-99mTc was obtained at >95% with excellent in-vitro and in-vivo stabilities. PEG-PAMAM G4-FA-5FU-99mTc was synthesized and the stability studies were carried out by the ITLC methods in serum (86.67% and 83.75%) and PBS. Combinational therapy effects of 5-FU and 99mTc containing nano-complexes were evaluated on 4 T1 (mouse breast cancer) and MDA-MB-231 (human breast adenocarcinoma) cancer cell lines. Excellent uptake values were obtained for FA-decorated nano-complexes on 4 T1 and MDA-MB-231 cell lines. Subsequently, tumor inhibition effects of PEG-PAMAM G4-FA-5FU-99mTc and PEG-PAMAM G4-FA-5FU were evaluated using the breast tumor-bearing BALB/C mice. Graphical abstract Breast Tumor Targeting with PAMAM-PEG-5FU- 99mTc As a New Therapeutic Nanocomplex: in In-vitro and In-vivo Studies was presented. This targeted drug delivery system can significantly increase the efficiency of cancer therapy, and reduce the treatment cost and time.

In vitro effect of branched polyethyleneimine (bPEI) on cells infected with human immunodeficiency virus: enhancement of viral replication.

Polyethyleneimine (PEI) is a chemical compound that used is as a carrier in gene therapy/delivery. Some studies have investigated the microbicidal potential and antiviral activity (prophylactic or therapeutic) of PEI and its derivatives. The aim of this study was to investigate the effect of branched polyethyleneimine (bPEI) on human immunodeficiency virus (HIV) replication. Infected cells were treated with bPEI for 36 hours, and the concentration of the viral protein P24 (as a virus replication marker) was determined in cell culture supernatants. This study indicated that bPEI increased HIV replication and decreased the viability of infected cells through cytotoxicity. The toxicity of bPEI its association with and cell death (apoptosis, autophagy and necrosis) have been reported in several studies. To investigate bPEI-induced cytotoxicity, we examined apoptosis and autophagy in cells treated with bPEI, and a significant increase in HIV viral load, the P24 antigen level, autophagy, and necrosis observed. Thus, treatment with bPEI leads to cytotoxicity and higher HIV virus yield.

A new colorimetric assay for amylase based on starch-supported Cu/Au nanocluster peroxidase-like activity.

In this paper, we present a new colorimetric technique as a novel assay for the easy and direct detection of α-amylase activity. This detection system utilizes the interaction of α-amylase with starch that is supporting copper/gold (Cu/Au) nanoclusters. The Cu/Au nanoclusters are synthesized using starch as a stabilizing agent at room temperature. These nanoclusters show robust peroxidase-like activity and are able to catalyze the oxidation of TMB (3,3,5,5-tetramethylbenzidine) in the presence of hydrogen peroxide (H2O2), leading to the generation of a blue-colored solution. The α-amylase detection mechanism is based on the digestion of the starch by α-amylase, which results in nanocluster aggregation, leading to increased nanoparticle size and thus decreased peroxidase-like activity of the Cu/Au NCs. Experiments showed that the gradual addition of α-amylase causes the peroxidase activity to decrease step by step in a linear fashion. Using this method, colorimetric sensing of α-amylase was achieved with a detection limit (LOD) of 0.04 U/mL and a linear range of 0.1-10 U/mL. This method is significantly selective for α-amylase and could be affordably and conveniently applied to the detection of α-amylase in blood serum. Graphical Abstract.

Inherent anti-HIV activity of biocompatible anionic citrate-PEG-citrate dendrimer.

The development of new combinations to empower better protection against HIV infection is particularly important. Anionic polymers can block HIV infection. In the current study, first generation (G1) and second generation (G2) novel water-soluble anionic citrate-PEG-citrate dendrimers were synthesized and characterized with Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy (NMR), and dynamic light scattering (DLS) methods. After the biocompatibility of the G2 dendrimer was determined, its antiviral activity was evaluated. This function may contribute to the peripheral groups of this dendrimer (carboxylate group). In order to measure the inhibitory effect of G2 on HIV infection, both pre-treatment (treated with G2 dendrimer before HIV infection) and co-treatment (simultaneously treated with G2 dendrimer and HIV infection) were used in vitro. The results showed the good synthesis of the G2 dendrimer, and the dendrimer showed antiviral properties (ICC50:0.4 mM) and low toxicity (CC50:0.6 mM) at high concentrations. A strong inhibitory effect was found when the co-treatment approach was used. This study achieved promising results which encourage the use of G2 dendrimers as anti-HIV agents.

Folic acid functionalized nanoparticles as pharmaceutical carriers in drug delivery systems.

Conventional chemotherapeutic approaches in cancer therapy such as surgery, chemotherapy, and radiotherapy have several disadvantages due to their nontargeted distributions in the whole body. On the other hand, nanoparticles (NPs) based therapies are remarkably progressing to solve several limitations of conventional drug delivery systems (DDSs) including nonspecific biodistribution and targeting, poor water solubility, weak bioavailability and biodegradability, low pharmacokinetic properties, and so forth. The enhanced permeability and retention effect escape from P-glycoprotein trap in cancer cells as a passive targeting mechanism, and active targeting strategies are also other most important advantages of NPs in cancer diagnosis and therapy. Folic acid (FA) is one of the biologic molecules which has been targeted overexpressed-folic acid receptor (FR) on the surface of cancer cells. Therefore, conjugation of FA to NPs most easily enhances the FR-mediated targeting delivery of therapeutic agents. Here, the recent works in FA which have been decorated NPs-based DDSs are discussed and cancer therapy potency of these NPs in clinical trials are presented.

Serum Levels of miR-155, miR-326, and miR-133b as Early Diagnostic Biomarkers for the Detection of Human Acute Heart Allograft Rejection in Comparison with Serum Cardiac Troponin T.

BACKGROUND: Acute heart allograft rejection occurs as a result of antibody-mediated rejection that presents during the first month after transplantation. Finding a non-invasive biomarker is essential for diagnosis of heart allograft rejection. In this research, we intended to compare expression levels of several microRNAs across cardiac troponin T levels between rejected patients (who died before one month following transplantation), non-rejected patients (who survived for at least one month after transplantation), and non-transplanted patients (CABG surgery patients). METHODS: Serum levels of miR-155, miR-326, and miR-133b were evaluated by the q-RT-PCR method. Furthermore, cardiac troponin T levels were measured by a highly sensitive electrochemiluminescence assay. Finally, the data were analyzed by independent sample t-test using SPSS 21® computer software. Results: It was observed that miR-326 and miR-155 expression levels increased after 24h and 72h of surgery in rejected patients compared with the two other groups, but these increases were not statistically significant. Moreover, the decrease in miR-133b expression level was non-significant after transplantation in the rejected group compared with the non-rejected group. However, cTnT levels in rejected patients increased significantly compared with the other groups (P < .05). After ROC curve analysis, the cTnT marker with the most area under the curve (AUC = 1.00, 95% confidence interval, 1.00 to 1.00; P = .006), had the best discriminatory power, and among microRNAs, miR-326 had the largest area under curve (AUC = 0.81), and consequently the highest discriminatory power. CONCLUSIONS: We demonstrated that troponin T can be a more efficient biomarker than miRNAs for early prediction of human death caused by acute heart rejection, and the ROC curves analysis verified this finding.

Colorimetric aptasensor for Campylobacter jejuni cells by exploiting the peroxidase like activity of Au@Pd nanoparticles.

The authors describe a method for colorimetric determination of Campylobacter jejuni (C. jejuni) in milk samples. It is based on the interaction of a specific DNA aptamer with surface protein in the cell membranes of C. jejuni. Specific binding of the aptamer with the cell membrane leads to an uptake of aptamer from solution. As a result, the concentration of aptamer floating in the solution is reduced. In the presence of large quantities of aptamer, the surface of added Au@Pd nanoparticles (NPs) is covered with aptamer via electrostatic interactions. Hence, they cannot act as a peroxidase mimic and oxidize the substrate 3,3',5,5'-tetramethylbenzidine (TMB) to give a blue product. However, when the aptamer is bound by the target cells, the surface of the NPs is not blocked by aptamer and the NPs exert a strong peroxidase -like activity. Under defined experimental conditions, the intensity of the blue color increases with the concentration of C. jejuni, and as little as 100 CFU·mL-1 can bedetected in milk. Graphical abstract A colorimetric aptasensor for assay Campylobacter jejuni whole cell in food samples was investigated. This assay was designed based on interaction of specific DNA aptamer with surface protein in c. jejuni cell membrane without any modification of aptamer.

A Systems Biology Approach to Understanding Alcoholic Liver Disease Molecular Mechanism: The Development of Static and Dynamic Models.

Alcoholic liver disease (ALD) is a complex disease characterized by damages to the liver and is the consequence of excessive alcohol consumption over years. Since this disease is associated with several pathway failures, pathway reconstruction and network analysis are likely to explicit the molecular basis of the disease. To this aim, in this paper, a network medicine approach was employed to integrate interactome (protein-protein interaction and signaling pathways) and transcriptome data to reconstruct both a static network of ALD and a dynamic model for it. Several data sources were exploited to assemble a set of ALD-associated genes which further was used for network reconstruction. Moreover, a comprehensive literature mining reveals that there are four signaling pathways with crosstalk (TLR4, NF- [Formula: see text]B, MAPK and Apoptosis) which play a major role in ALD. These four pathways were exploited to reconstruct a dynamic model of ALD. The results assure that these two models are consistent with a number of experimental observations. The static network of ALD and its dynamic model are the first models provided for ALD which offer potentially valuable information for researchers in this field.

Selection of specific inhibitor peptides in enzyme-linked immunosorbent assay (ELISA) of cardiac troponin I using immuno-dominant epitopes as competitor.

Human cardiac troponin I (cTni) is the gold marker for early diagnosis of myocardial infarction. In this regard, four immune-dominant epitopes of cTni were predicted and their 3D structures were determined. Thereafter, the competitive performance of the peptides was monitored with the developed polyclonal antibody-based indirect competitive ELISA; a half-maximal inhibitory concentration (IC50) of 0.49 (µg/mL) and detection limit of 0.037 (µg/mL) were achieved for recombinant cTni. The competitive ELISA determined sensitivity levels of 0.306, 0.141, 0.960, and 0.155 (µg/mL), respectively, for each peptide as competitor. We indicated that two of the selected epitopes have significant sensitivity scales and inhibition ability.

Chitosan-Albumin Nanocomposite as a Promising Nanocarrier for Efficient Delivery of Fluconazole Against Vaginal Candidiasis.

Currently, the high incidence of fungal infections among females has resulted in outstanding problems. Candida species is related with multidrug resistance and destitute clinical consequences. Chitosan-albumin derivatives with more stability exhibit innate antifungal and antibacterial effects that boost the activity of the drug without inflammatory impact. The stability and sustained release of Fluconazole in mucosal tissues can be ensured by encapsulating in protein/polysaccharide nanocomposites. Thus, we developed chitosan-albumin nanocomposite (CS-A) loaded with Fluconazole (Flu) antifungals against vaginal candidiasis. Various ratios of CS/Flu (1:1, 1:2, 2:1) were prepared. Thereafter, the CS-A-Flu nanocomposites were qualified and quantified using FT-IR, DLS, TEM, and SEM analytical devices, and the size range from 60 to 100 nm in diameter was attained for the synthesized nanocarriers. Afterward, the antifungal activity, biofilm reduction potency, and cell viability assay were performed for biomedical evaluation of formulations. The minimum inhibitory concentration) and minimum fungicidal concentration on Candida albicans were attained at 125 ng/µL and 150 ng/µL after treatment with a 1:2 (CS/Flu) ratio of CS-A-Flu. The biofilm reduction assay indicated that biofilm formation was between 0.05 and 0.1% for CS-A-Flu at all ratios. The MTT assay also exhibited excellent biocompatibility for samples, about 7 to 14% toxicity on human HGF normal cells. These data have indicated that CS-A-Flu would be a promising candidate against Candida albicans.

Bifunctional folic acid targeted biopolymer Ag@NMOF nanocomposite [{Zn2 (1,4-bdc) 2 (DABCO)} n] as a novel theranostic agent for molecular imaging of colon cancer by SERS.

Without a doubt, cancer and its negative impact on human health have created many hurdles for people across the world since conventional approaches have not offered a reliable ability in the eradication of cancer. As a result, finding novel approaches, like using bimodal nanoparticles as a potential nanocarrier in molecular imaging and cancer therapy, is remarkably required these days. In the present study, ex-situ (Ge) and in-situ (Gi) green synthesized silver (Ag) nanoparticles entrapped in metal-organic framework nanocomposites (NMOF) coated with folic acid (FA) targeted chitosan (CS) was successfully developed as a novel bifunctional nanocarrier for detection and treatment of colon cancer cells. Then nanocarriers, such as NMOF-CS-FA, Ge-Ag@NMOF-CS-FA, Gi-Ag@NMOF-CS-FA, and C-Ag@NMOF-CS-FA, were characterized via FT-IR, DLS, SERS, TEM, and SEM and results have potentially confirmed the quality and quantity of synthesized nanocomposites. The hydrodynamic diameters of NMOF-CS, Ge-Ag@NMOF-CS, Gi-Ag@NMOF-CS, and C-Ag@NMOF-CS specimens were measured at around 99.7 ± 10 nm, 110 ± 10 nm, 118 ± 10 nm, 115 ± 10 nm, respectively. Also, the PDI values less than 0.2 confirm the reliable distribution of these nanocomposites. Afterward, the cell viability assay was conducted on HCT116 and HGF cell lines for evaluating biocompatibility and targeting efficiency of nanocomposites; FA functionalized nanocomposites have intensively indicated better performance in cancer cells targeting and their inhibition, and IC50 was attained for 10 ng/mL of Ge-Ag@NMOF-CS-FA while non-targeted nanocarriers did not have toxicity more than 20 % on HCT116 colon cancer cells. Moreover, according to the results, the cell viability of HGF normal cells was at least 85 % after being exposed to different concentrations of nanocomposites for 24 h. This indicates that the synthesized nanocomposites do not have significant toxic effects on normal cells. The results indicate that this novel nanocomposite has the potential to effectively deliver drugs to cancer cells.

The effects of metformin and PCL-sorafenib nanoparticle co-treatment on MCF-7 cell culture model of breast cancer.

Despite breakthrough therapeutics in breast cancer, it is one of the main causes of mortality among women worldwide. Thus, drug therapies for treating breast cancer have recently been developed by scientists. Metformin and sorafenib are well-known therapeutics in breast cancer. In the present study, we combined sorafenib and PCL-sorafenib with metformin to improve drug absorption and promote therapeutic efficiency. The MCF-7 cells were treated with metformin, sorafenib, or PCL-sorafenib. The growth inhibitory effect of these drugs and cell viability were assessed using MTT and flow cytometry assays, respectively. The expression of targeted genes involved in cell proliferation, signaling, and the cell cycle was measured by real-time PCR. The results showed that MCF-7 cells treated with metformin/sorafenib and PCL-sorafenib/metformin co-treatment contributed to 50% viability compared to the untreated group. Moreover, PI and Annexin V staining tests showed that the cell viability for metformin/sorafenib and PCL-sorafenib/metformin was 38% and 17%, respectively. Furthermore, sorafenib/metformin and PCL-sorafenib/metformin lead to p53 gene expression increase by which they can increase ROS, thereby decreasing GPX4 gene expression. In addition, they affected the expression of BCL2 and BAX genes and altered the cell cycle. Together, the combination of PCL-sorafenib/metformin and sorafenib/metformin increased sorafenib absorption at lower doses and also led to apoptosis and oxidative stress increases in MCF-7 cells.

Fluorescence self-assembled DNA hydrogel for the determination of prostate specific antigen by aggregation induced emission.

In this study, an aptamer-based, functionalized-DNA hydrogel system is developed for prostate-specific antigen (PSA) detection. A pure DNA hydrogel is constructed using specific DNA building blocks and an aptamer as a cross-linker. Firstly, silver nanoclusters (AgNCs) are constructed on the Y-shaped DNA (Y-DNA) building blocks. Then, the DNA hydrogel was formed via the addition of the cross-linker to the Y-DNA solution. In this case, the fluorescence emission of silver nanoclusters that have accumulated in the hydrogel increases due to aggregation-induced emission (AIE). The presence of PSA and its subsequent interaction with its specific aptamer dissolve the hydrogel structures, which leads to a low emission intensity. A great linear relationship was attained in this assay in the range of 0.05 to 8 ng mL-1 with a detection limit of 4.4 pg mL-1 for the detection of PSA. Additionally, the proposed aptasensor was successfully used to detect PSA in human serum samples. The recovery for different concentrations of PSA was in the range of 96.1% to 99.3%, and the RSD range was from 2.3% to 4.5%. Comparing our method to current ones in the field of PSA detection proves that our platform benefits from a simpler procedure, lower cost, and better efficiency, providing high potential for future clinical applications.

Poly lactic-co-glycolic acid-alginate nanocarrier for efficient drug delivery to liver cancer cells.

Efficient drug delivery systems (DDSs) can potentially replace with conventional modalities in cancer therapy, like liver cancer. In this study, a novel folic acid (FA)-functionalised and alginate (Alg)-modified poly lactic-co-glycolic acid (PLGA) nanocomposite was developed for delivery of doxorubicin (Dox) to HepG2 and Huh7 liver cancer cells. After synthesising the nanocarrier, several analytical devices, including FT-IR, DLS, TGA, and TEM, were employed for its characterisation. Nano-metric size (55 and 85 nm in diameter), close to neutral surface charge, semi-spherical morphology, and successful synthesis were approved. Dox entrapment efficiency was determined near 1%, and sustained and pH-sensitive drug release behaviours of nanocarrier were ascertained for DDS. Afterwards, the cell viability test was carried out to study the HepG2 and Huh7 cells suppression capability of FA-PLGA-Dox-Alg. About 12% and 10% cell viabilities were observed in HepG2 and Huh7 cancer cells after 24 h treatment with 400 nM concentration of FA-PLGA-Dox-Alg nanocarrier respectively. The IC50 value was observed for 100 nM after 24 h of treatment in cancer cells. These data have indicated that fabricated nanocarrier could be promising DDS against liver cancer and replace with conventional approaches in cancer treatment, like chemotherapy.

Label-Free Detection of Cardiac Biomarkers: A Review on Microfluidic Electrochemical Biosensors.

Biosensors are valuable tools for the detection of biological species, including cells, pathogens, proteins, and other biological molecules. Biosensing devices integrated with microfluidics not only allow for easier sample preparation, portability, and reduced detection time and cost but also offer unique features such as label-free detection and improved sensitivity. Cardiovascular diseases (CVDs), particularly acute myocardial infarction, which is considered one of the main causes of death, are currently diagnosed by electrocardiography (ECG), which has been proven to be inadequate. To overcome the limitations of ECG, the efficient detection of cardiac biomarkers and specifically the measurement of cardiac troponins (cTnT and cTnI) are suggested. This review aims to expound on microfluidics, the most recent materials to develop these devices, and their application in medical diagnosis, particularly in CVD detection. Moreover, we will explore some of the prevalent and last readout methods to investigate in-depth electrochemical label-free detection methods for CVDs, primarily based on voltammetry and electrochemical impedance spectroscopy, with the main focus on structural details.