Robust Wet Milling Technique for Producing Micronized Ibuprofen Particles with Improved Solubility and Dissolution.

This study investigated a systematic approach for producing ibuprofen (IBF) particles with leucine by wet milling. Using a high shear homogenizer, the particles size of the IBF was reduced. Prepared IBF microparticles were freeze-dried and characterized by using Mastersizer, SEM, DSC, XRD, ATR-FTIR, and TGA. The drug saturation solubility and in-vitro dissolution performance were carried out in phosphate buffer solution (PBS, pH 7.4) at 37°C temperature and IBF were determined using a validated HPLC method. The wet-milled method reduced the particle size from 71.3 to 1.7 µm. The minimum particle size of IBF was obtained in 0.05% Tween 80 solution homogenized at 17,000 rpm for 15 min. The saturated solubility (168.7 µg/mL) of the micronized IBF particles with leucine showed higher compared to that of the original IBF (147.4 µg/mL) in PBS solution. The prepared IBF particles containing 2.5-6.25% leucine showed significantly higher IBF release (100%) compared to that of original drug particles (55.9%) in 120 min. The excipient leucine played a major role in enhancing the solubility and dissolution profile of the prepared IBF particles probably by the formation of hydrogen bonding. The developed wet milling was an efficient and robust technique for reducing the particle size of IBF and could be a useful method for manufacturing drug particles with enhanced solubility and dissolution.

Rapid and selective detection of recombinant human erythropoietin in human blood plasma by a sensitive optical sensor.

Recombinant human erythropoietin (rHuEPO) is an important hormone drug that is used to treat several medical conditions. It is also frequently abused by athletes as a performance enhancing agent at sporting events. The time window of the rHuEPO in blood is short. Therefore, the rapid detection of rHuEPO use/abuse at points of care and in sports requires a selective analytical method and a sensitive sensor. Herein, we present a highly selective method for the rapid detection of rHuEPO in human blood plasma by a sensitive optical sensor. rHuEPO is selectively extracted from human blood plasma by a target-specific extractor chip and converted into a biothiol by reducing its disulfide bond structure. The formed biothiol reacts with a water soluble (E)-1-((6-methoxybenzo[d]thiazole-2-yl)diazenyl)naphthalene-2,6-diolHg(ii) (BAN-Hg) optical sensor and causes its rapid decomposition. This leads to a rapid change in the sensor color from blue to pink that can be observed by the naked eye. The optical sensor was used to quantify rHuEPO in the concentration range 1 × 10-8 M to 1 × 10-12 M by UV-Vis spectroscopy. For the screening of blood plasma, an EPO-specific extractor chip was synthesized and used to selectively extract the protein from the biological matrix prior to its conversion into biothiol and quantification by the optical sensor. Since many proteins have a disulfide bond structure, the new method has strong potential for their rapid sensitive and selective detection by the BAN-Hg sensor and UV-Vis spectroscopy.

Dual chemosensor for the rapid detection of mercury(ii) pollution and biothiols.

A new benzothiazole azo dye [(E)-1-((6-methoxybenzo[d]thiazole-2-yl)diazenyl)naphthalene-2,6-diol] (also known as "BAN"), has been synthesised and used as a chemosensor for the rapid and selective detection of mercury(ii) ions in water. The pink coloured chemosensor turns blue when reacted with mercury(ii) ions due to the formation of a 2 : 1 coordination complex. The complex formation causes a bathochromic shift of the chemosensor's UV absorption peak from 540 to 585 nm and turns on a highly selective fluorescence emission at 425 nm. The change in the optical property of BAN upon complexation with mercury(ii) was confirmed by ab initio calculations. The new chemosensor was used to quantify mercury(ii) ions in water by fluorescence spectroscopy down to 5 × 10-8 M (10 ppb). The limit of detection (LOD) of Hg2+ was 9.45 nM (1.8 ppb) which satisfies the maximum allowable Hg2+ concentration in drinking water that is set by the WHO. The BAN-Hg(ii) complex was used for the determination of cysteine (Cys) in aqueous solution by UV-Vis spectroscopy down to 1 × 10-7 M. The thiol-containing amino acid preferentially coordinates the mercury ions of the BAN-Hg(ii) complex. This causes dissociation of the blue-coloured complex and the liberation of the pink-coloured BAN dye. The colour change of the BAN-Hg(ii) complex from blue to pink was selective to the Cys biothiol while other non-thiol containing amino acids did not cause a colour change. For the in-field application, filter paper strips were loaded with the BAN-Hg(ii) complex and used as a disposable sensor for the detection of cysteine (Cys) by the naked eye. Therefore, the BAN chemosensor offers a sensitive, and rapid tool for the detection of mercury(ii) in water. In addition, the BAN-Hg(ii) complex can be used as a simple and selective chemosensor of the screening of purified biothiols, such cysetine, homocysteine and glutathione in biology research and pharmaceutical/food industries.

Preconcentration and SERS-based determination of infliximab in blood by using a TNF-α-modified gold-coated copper oxide nanomaterial.

Infliximab (INF) is a chimeric monoclonal immunoglobulin acting against tumor necrosis factor-alpha (TNF-α). The drug is used for the treatment of chronic autoimmune and inflammatory diseases. A target-specific nanomaterial is presented for the extraction of INF from human plasma along with a label-free surface enhanced Raman spectroscopy (SERS) method for its determination using a handheld device. A gold-coated copper oxide chip was functionalized with TNF-α and used to extract the drug from plasma. INF was recovered from the extractor by lowering the pH value to 2.5. The disulfide bond structure of the drug was then reduced and used for its oriented chemisorption onto a gold-coated copper oxide substrate for SERS measurements using the INF-specific band at 936 cm-1. The working range of the SERS method was between 10-7 and 10-14 M of reduced INF. The relative standard deviation (RSD), between three different measurements was 4.2% (intra-day) and 7.1% (inter-day). The quantification and detection limits of the assay (LOQ, LOD) were 0.01 pM and 1.4 fM respectively. The SERS detection was cross-validated against ELISA where 99% agreement was found between the two methods. Graphical abstractSchematic representation of the determination of Infliximab (INF) in blood. A gold coated copper oxide chip was functionalised with tumor necrosis factor (TNF-α) and used to extract INF from blood plasma. The captured INF was released, reduced, chemisorbed onto a second gold-coated copper oxide substrate and screened by surface-enhanced Raman spectroscopy (SERS) using a handheld device.

Spectroelectrochemical Nanosensor for the Determination of Cystatin C in Human Blood.

The detection of protein biomarkers for the clinical diagnosis of diseases requires selective and sensitive methodologies and biosensors that can be easily used at pathology laboratories and points of care. An ideal methodology would be able to conduct multimode screening of low and high concentrations of proteins in biological fluids using recyclable platforms. In this work, we demonstrate a novel nanosensing methodology for the dual detection of cystatin C (CST-C), as a protein biomarker model, in blood plasma by surface-enhanced Raman spectroscopy and electrochemistry. The new methodology utilizes the thiol chemistry of biomolecules to develop a target-specific and recyclable extractor chip for the rapid isolation of protein biomarkers from blood plasma. This is followed by the rapid reduction of the disulfide bonds within the isolated protein to influence its oriented immobilization onto a conductive gold coated silicon nanopillar substrate via stable gold-sulfur (Au-S) bonds. The oriented immobilization led to reproducible surface-enhanced Raman spectroscopy (SERS) measurements of the reduced protein (RSD = 3.8%) and allowed for its direct electrochemical determination. After the SERS measurement, differential pulse voltammetry (DPV) was used to desorb the analyte from the substrate and generate a reduction current that is proportional to its concentration. CST-C was determined down to 1 pM and 62.5 nM by SERS and DPV, respectively, which satisfies the requirements for monitoring Alzheimer's and kidney failure diseases. The new dual nanosensing methodology has strong potential for miniaturization in a lab-on-a-chip platform for the screening of many protein biomarkers that have a disulfide bond structure.

Mixed Polymer-Coated Magnetic Nanoparticles as Forward Osmosis Draw Agents of Tuned Hydrophilicity.

We recently reported a polymer-coated magnetic nanoparticle (MNP) draw agent for the forward osmosis (FO) water desalination process. The water flux was found to increase when the polymer poly(sodium acrylate) (PSA) was anchored to the MNP surface as compared to the polymer (or polyelectrolyte solution) alone, due to the polymer chains being stretched out and most of the hydrophilic groups on the polymer contributing to water flux. We herein report the use of a secondary polymer poly(N-isopropylacrylamide) PNIPAM to manipulate the PSA polymer conformation and influence inter- and intrachain interactions to enhance the efficiency of the FO draw agent. These PSA-PNIPAM-coated MNPs generated a much higher water flux of ∼11.66 LMH when compared to the 100 % PSA-coated MNPs featuring a value of ∼5.32 LMH under identical FO conditions. The osmotic pressure and water flux driven by the mixed polymer-coated MNPs were found to be a strong function of the net polymer coverage on MNPs, that is, net available hydrophilic groups. Our new draw agent demonstrates potential for use in the water industry due to its improved efficiency and cost effectiveness as it uses only ∼0.062 % (w/v) of the draw agent solution.

Rapid isolation and detection of erythropoietin in blood plasma by magnetic core gold nanoparticles and portable Raman spectroscopy.

Isolating, purifying, and identifying proteins in complex biological matrices are often difficult, time consuming, and unreliable. Herein we describe a rapid screening technique for proteins in biological matrices that combines selective protein isolation with direct surface enhanced Raman spectroscopy (SERS) detection. Magnetic core gold nanoparticles were synthesized, characterized, and subsequently functionalized with recombinant human erythropoietin (rHuEPO)-specific antibody. The functionalized nanoparticles were used to capture rHuEPO from horse blood plasma within 15 min. The selective binding between the protein and the functionalized nanoparticles was monitored by SERS. The purified protein was then released from the nanoparticles' surface and directly spectroscopically identified on a commercial nanopillar SERS substrate. ELISA independently confirmed the SERS identification and quantified the released rHuEPO. Finally, the direct SERS detection of the extracted protein was successfully demonstrated for in-field screening by a handheld Raman spectrometer within 1 min sample measurement time. FROM THE CLINICAL EDITOR: The rapid detection of recombinant human erythropoietin (rHuEPO) is important in competitive sports to screen for doping offences. In this article, the authors reported their technique of direct surface enhanced Raman spectroscopy (SERS) detection using magnetic core gold nanoparticles functionalized with recombinant human erythropoietin-specific antibody. The findings should open a new way for future detection of other proteins.

Towards improved precision in the quantification of surface-enhanced Raman scattering (SERS) enhancement factors: a renewed approach.

This paper demonstrates a renewed procedure for the quantification of surface-enhanced Raman scattering (SERS) enhancement factors with improved precision. The principle of this method relies on deducting the resonance Raman scattering (RRS) contribution from surface-enhanced resonance Raman scattering (SERRS) to end up with the surface enhancement (SERS) effect alone. We employed 1,8,15,22-tetraaminophthalocyanato-cobalt(II) (4α-Co(II)TAPc), a resonance Raman- and electrochemically redox-active chromophore, as a probe molecule for RRS and SERRS experiments. The number of 4α-Co(II)TAPc molecules contributing to RRS and SERRS phenomena on plasmon inactive glassy carbon (GC) and plasmon active GC/Au surfaces, respectively, has been precisely estimated by cyclic voltammetry experiments. Furthermore, the SERS substrate enhancement factor (SSEF) quantified by our approach is compared with the traditionally employed methods. We also demonstrate that the present approach of SSEF quantification can be applied for any kind of different SERS substrates by choosing an appropriate laser line and probe molecule.

Correction: Towards improved precision in the quantification of surface-enhanced Raman scattering (SERS) enhancement factors: a renewed approach.

Correction for 'Towards improved precision in the quantification of surface-enhanced Raman scattering (SERS) enhancement factors: a renewed approach' by Arumugam Sivanesan et al., Analyst, 2015, DOI:10.1039/c4an01778a

Reproducible and label-free biosensor for the selective extraction and rapid detection of proteins in biological fluids.

Erythropoietin (EPO), a glycoprotein hormone of ∼ 34 kDa, is an important hematopoietic growth factor, mainly produced in the kidney and controls the number of red blood cells circulating in the blood stream. Sensitive and rapid recombinant human EPO (rHuEPO) detection tools that improve on the current laborious EPO detection techniques are in high demand for both clinical and sports industry. A sensitive aptamer-functionalized biosensor (aptasensor) has been developed by controlled growth of gold nanostructures (AuNS) over a gold substrate (pAu/AuNS). The aptasensor selectively binds to rHuEPO and, therefore, was used to extract and detect the drug from horse plasma by surface enhanced Raman spectroscopy (SERS). Due to the nanogap separation between the nanostructures, the high population and distribution of hot spots on the pAu/AuNS substrate surface, strong signal enhancement was acquired. By using wide area illumination (WAI) setting for the Raman detection, a low RSD of 4.92% over 150 SERS measurements was achieved. The significant reproducibility of the new biosensor addresses the serious problem of SERS signal inconsistency that hampers the use of the technique in the field. The WAI setting is compatible with handheld Raman devices. Therefore, the new aptasensor can be used for the selective extraction of rHuEPO from biological fluids and subsequently screened with handheld Raman spectrometer for SERS based in-field protein detection.

Rapidly and simply detecting Cr (VI) in aqueous media via a diketopyrrolopyrrole-based chemosensor with both high selectivity and low LOD.

BACKGROUND: The high toxicity of hexavalent chromium [Cr (VI)] could not only cause harmful effects on humans, including carcinogenicity, respiratory issues, genetic damage, and skin irritation, but also contaminate drinking water sources, aquatic ecosystems, and soil, impairing the reproductive capacity, growth, and survival of organisms. Due to these harmful effects, detecting toxic Cr (VI) is of great significance. However, the rapid, simple, and efficient detection at a low Cr (VI) concentration is extremely challenging, especially in an acidic condition (existing as HCrO4-) due to its low adsorption free energy. RESULTS: A diketopyrrolopyrrole-based small molecule (DPPT-PhSMe) is designed and characterized to act as a chemosensor, which allows a high selectivity to Cr (VI) at an acidic condition with a low limit of detection to 10-8 M that is two orders of magnitude lower than the cut of limit (1 µM) recommended by World Health Organization (WHO). Mechanism study indicates that the rich sulfur atoms enhance the affinity to HCrO4-. Combining with favorable features of diketopyrrolopyrrole, DPPT-PhSMe not only allows dual-mode detection (colorimetric and spectroscopic) to Cr (VI), but also enables disposable paper-based sensor for naked-eye detection to Cr (VI) from fully aqueous media. The investigation of DPPT-PhSMe chemosensor for the quantification of Cr (VI) in real life samples demonstrates a high reliability and accuracy with an average percentage recovery of 102.1 % ± 4 (n = 3). SIGNIFICANCE: DPPT-PhSMe represents the first diketopyrrolopyrrole-derived chemosensor for efficient detection to toxic Cr (VI), not only providing a targeted solution to the bottleneck of Cr (VI) detection in acidic conditions (existing as HCrO4-) caused by its low adsorption free energy, but also opening a new scenario for simple, selective, and efficient Cr (VI) detection with conjugated dye molecules.

Paper electrochemical immunosensor for the rapid screening of Galectin-3 patients with heart failure.

A paper electrochemical immunosensor for the combined binding and quantification of the heart failure (HF) biomarker Galectin-3 has been developed. The simple design of the new sensor is comprised of paper material that is decorated with gold nanostructures, to maximize its electroactive surface area, and functionalized with target-specific recognition molecules to selectively bind the protein from aqueous solutions. The binding of the protein caused the blockage of the electron flow to the sensor electroactive surface, thus causing its oxidation potential to shift and the corresponding current to reduce quantitatively with the increase in the protein concentration within the working range of 0.5ng/mL-8ng/mL (LOQ-0.5 ng/mL). This novel sensor was able to quantify Galectin-3 concentration in saliva samples from HF patients and healthy controls within 20 min with good reproducibility (RSD = 3.64%), without the need for complex sample processing steps. The electrochemical measurements of the patient samples were cross validated by ELISA where the percent agreement between the two methods was found to be 92.7% (RSD = 7.20%). Therefore, the new paper immunosensor sensor has a strong potential for rapid and cost-effective screening of the Galectin 3 biomarker at points of care, thus supporting the timely diagnosis of heart failure.

Impact of Leucine and Magnesium Stearate on the Physicochemical Properties and Aerosolization Behavior of Wet Milled Inhalable Ibuprofen Microparticles for Developing Dry Powder Inhaler Formulation.

This study investigated the development and characterization of leucine and magnesium stearate (MgSt) embedded wet milled inhalable ibuprofen (IBF) dry powder inhaler (DPI) formulations. IBF microparticles were prepared by a wet milling homogenization process and were characterized by SEM, FTIR, DSC, XRD and TGA. Using a Twin-Stage Impinger (TSI), the in vitro aerosolization of the formulations with and without carrier lactose was studied at a flow rate of 60± 5 L/min and the IBF was determined using a validated HPLC method. The flow properties were determined by the Carr's Index (CI), Hausner Ratio (HR) and Angle of Repose (AR) of the milled IBF with 4-6.25% leucine and leucine containing formulations showed higher flow property than those of formulations without leucine. The fine particle fraction (FPF) of IBF from the prepared formulations was significantly (p = 0.000278) higher (37.1 ± 3.8%) compared to the original drug (FPF 3.7 ± 0.9%) owing to the presence of leucine, which enhanced the aerosolization of the milled IBF particles. Using quantitative phase analysis, the XPRD data revealed the crystallinity and accurate weight percentages of the milled IBF in the formulations. FTIR revealed no changes of the structural integrity of the milled IBF in presence of leucine or MgSt. The presence of 2.5% MgSt in the selected formulations produced the highest solubility (252.8 ± 0.6 µg/mL) of IBF compared to that of unmilled IBF (147.4 ± 1.6 µg/mL). The drug dissolution from all formulations containing 4-6.25% leucine showed 12.2-18.6% drug release in 2.5 min; however, 100% IBF dissolution occurred in 2 h whereas around 50% original and dry milled IBF dissolved in 2 h. The results indicated the successful preparation of inhalable IBF microparticles by the wet milling method and the developed DPI formulations with enhanced aerosolization and solubility due to the presence of leucine may be considered as future IBF formulations for inhalation.

Combined time- and space-resolved Raman spectrometer for the non-invasive depth profiling of chemical hazards.

A time-resolved inverse spatially offset Raman spectrometer was constructed for depth profiling of Raman-active substances under both the lab and the field environments. The system operating principles and performance are discussed along with its advantages relative to traditional continuous wave spatially offset Raman spectrometer. The developed spectrometer uses a combination of space- and time-resolved detection in order to obtain high-quality Raman spectra from substances hidden behind coloured opaque surface layers, such as plastic and garments, with a single measurement. The time-gated spatially offset Raman spectrometer was successfully used to detect concealed explosives and drug precursors under incandescent and fluorescent background light as well as under daylight. The average screening time was 50 s per measurement. The excitation energy requirements were relatively low (20 mW) which makes the probe safe for screening hazardous substances. The unit has been designed with nanosecond laser excitation and gated detection, making it of lower cost and complexity than previous picosecond-based systems, to provide a functional platform for in-line or in-field sensing of chemical substances.

Label-free identification of Erythropoietin isoforms by surface enhanced Raman spectroscopy.

We present a sensitive label-free surface enhanced Raman spectroscopy (SERS) method for the discrimination between the recombinant and endogenous human Erythropoietin (EPO) isoforms. The proposed methodology comprises a lectin-functionalised extractor chip for the extraction of the recombinant human EPO (rhuEPO) and the endogenous EPO (enEPO) from blood plasma. The disulfide bond molecular structure of the purified isoforms was modified to chemisorb the biomolecules onto a SERS substrate in a unified orientation, thus maximizing the reproducibility and sensitivity of the SERS measurements. The acquired SERS spectra of the EPO isoforms showed diagnostic Raman bands that allowed for the discrimination between rhuEPO and enEPO. The method was also used for the SERS quantification of rhuEPO and enEPO down to 0.1 pM and 0.5 pM, respectively. The SERS determination of the protein isoforms was cross validated against ELISA. The new SERS method has strong potential for the rapid screening of rhuEPO doping in athletes and for the therapeutic drug monitoring of rhuEPO treatment in cancer patients.

Application of Mesoporous Silica Nanoparticles in Cancer Therapy and Delivery of Repurposed Anthelmintics for Cancer Therapy.

This review focuses on the biomedical application of mesoporous silica nanoparticles (MSNs), mainly focusing on the therapeutic application of MSNs for cancer treatment and specifically on overcoming the challenges of currently available anthelmintics (e.g., low water solubility) as repurposed drugs for cancer treatment. MSNs, due to their promising features, such as tunable pore size and volume, ability to control the drug release, and ability to convert the crystalline state of drugs to an amorphous state, are appropriate carriers for drug delivery with the improved solubility of hydrophobic drugs. The biomedical applications of MSNs can be further improved by the development of MSN-based multimodal anticancer therapeutics (e.g., photosensitizer-, photothermal-, and chemotherapeutics-modified MSNs) and chemical modifications, such as poly ethyleneglycol (PEG)ylation. In this review, various applications of MSNs (photodynamic and sonodynamic therapies, chemotherapy, radiation therapy, gene therapy, immunotherapy) and, in particular, as the carrier of anthelmintics for cancer therapy have been discussed. Additionally, the issues related to the safety of these nanoparticles have been deeply discussed. According to the findings of this literature review, the applications of MSN nanosystems for cancer therapy are a promising approach to improving the efficacy of the diagnostic and chemotherapeutic agents. Moreover, the MSN systems seem to be an efficient strategy to further help to decrease treatment costs by reducing the drug dose.

Towards Label-free detection of viral disease agents through their cell surface proteins: Rapid screening SARS-CoV-2 in biological specimens.

Current methods for the screening of viral infections in clinical settings, such as reverse transcription polymerase chain reaction (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA), are expensive, time-consuming, require trained personnel and sophisticated instruments. Therefore, novel sensors that can save time and cost are required specially in remote areas and developing countries that may lack the advanced scientific infrastructure for this task. In this work, we present a sensitive, and highly specific biosensing approach for the detection of harmful viruses that have cysteine residues within the structure of their cell surface proteins. We utilized new method for the rapid screening of SARS-CoV-2 virus in biological fluids through its S1 protein by surface enhanced Raman spectroscopy (SERS). The protein is captured from aqueous solutions and biological specimens using a target-specific extractor substrate. The structure of the purified protein is then modified to convert it into a bio-thiol by breaking the disulfide bonds and freeing up the sulfhydryl (SH) groups of the cysteine residues. The formed biothiol chemisorbs favourably onto a highly sensitive plasmonic sensor and probed by a handheld Raman device in few seconds. The new method was used to screen the S1 protein in aqueous medium, spiked human blood plasma, mucus, and saliva samples down to 150 fg/L. The label-free SERS biosensing method has strong potential for the fingerprint identification many viruses (e.g. the human immunodeficiency virus, the human polyomavirus, the human papilloma virus, the adeno associated viruses, the enteroviruses) through the cysteine residues of their capsid proteins. The new method can be applied at points of care (POC) in remote areas and developing countries lacking sophisticated scientific infrastructure.

ß-Lactoglobulin-Modified Mesoporous Silica Nanoparticles: A Promising Carrier for the Targeted Delivery of Fenbendazole into Prostate Cancer Cells.

The clinical utilization of fenbendazole (FBZ) as a potential anticancer drug has been limited due to its low water solubility, which causes its low bioavailability. The development of a drug nanoformulation that includes the solubilizing agent as a drug carrier can improve solubility and bioavailability. In this study, Mobil Composition of Matter Number 48 (MCM-48) nanoparticles were synthesized and functionalized with succinylated ß-lactoglobulin (BLG) to prevent early-burst drug release. The BLG-modified amine-functionalized MCM-48 (MCM-BLG) nanoparticles were loaded with FBZ to produce the drug nanoformulation (FBZ-MCM-BLG) and improved the water solubility and, consequently, its anticancer effects against human prostate cancer PC-3 cells. The prepared FBZ-MCM-BLG was characterized in terms of size, zeta potential, drug loading capacity, morphology, thermal and chemical analyses, drug release, cellular uptake, cell viability, cell proliferation, production of reactive oxygen species (ROS), and cell migration. The results demonstrated that the FBZ-MCM-BLG nanoparticles have a spherical morphology with a size and zeta potential of 369 ± 28 nm and 28 ± 0.4 mV, respectively. The drug loading efficiency of the new nanoformulation was 19%. The release of FBZ was pH-dependent; a maximum cumulative release of about 76 and 62% in 12 h and a burst release of 53 and 38% in the first 0.5 h was observed at pH 1.2 and 6.8, respectively. The prepared FBZ-MCM-BLG formulation demonstrated higher cytotoxicity effects against PC-3 cells by 5.6- and 1.8-fold, respectively, when compared to FBZ and FBZ-MCM nanoparticles. The new formulation also increased the production of ROS by 1.6- and 1.2-fold and inhibited the migration of PC-3 cells when compared to the FBZ and FBZ-MCM nanoparticles, respectively. Overall, FBZ-MCM-BLG nanoparticles improved FBZ delivery to PC-3 cells and have the potential to be evaluated for the treatment of prostate cancer following a comprehensive in vivo study.

Development of Thiabendazole-Loaded Mesoporous Silica Nanoparticles for Cancer Therapy.

Thiabendazole (TBZ) is an anthelmintic drug currently studied for anticancer purposes. However, due to its low solubility, its biomedical application has been limited. Using mesoporous silica nanoparticles (MSNPs), such as Mobil Composition of Matter Number 41 (MCM-41), as a drug carrier, is a promising approach to improve the solubility of low water-soluble drugs. In the present work, we aim to develop TBZ-loaded MCM-41 (TBZ MCM-41) nanoparticles to improve the solubility and the therapeutic efficacy of TBZ against prostate cancer PC-3 cells. TBZ MCM-41 nanoparticles were synthesized with a size of 215.9 ± 0.07 nm, a spherical shape, a hexagonal array of channels, and a drug loading capacity of 19.1%. The biological effects of the nanoformulation on PC-3 cells were then evaluated using a 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT), IncuCyte live-cell imaging system, cell migration, and reactive oxygen species (ROS) assays. The results demonstrated that TBZ was released from MCM-41 nanoparticles in a controlled manner at pH values of 1.2 and 6.8. The cell viability measurements revealed that the TBZ MCM-41 nanoparticles caused a considerable 2.8-fold increase in the cytotoxicity of TBZ (IC50 127.3 and 46 µM for TBZ and TBZ MCM-41 nanoparticles, respectively). The results of the proliferation assay were in agreement with those of the cell viability measurements, where the MCM-41 increased the cytotoxicity of TBZ in a concentration-dependent manner. Also, the TBZ MCM-41 nanoparticles were found to enhance the potency of the drug and inhibit PC-3 cell migration. In addition, the ROS assay confirmed that TBZ MCM-41 nanoparticles were approximately 15% more potent than TBZ to produce ROS. Overall, the results demonstrated that MCM-41 nanoparticles are a promising carrier to improve the therapeutic efficacy of TBZ against PC-3 cells and suggest evaluating the efficacy of the formulation in vivo.

A paper-based optical sensor for the screening of viruses through the cysteine residues of their surface proteins: A proof of concept on the detection of coronavirus infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a serious threat to human health. Current methods such as reverse transcription polymerase chain reaction (qRT-PCR) are complex, expensive, and time-consuming. Rapid, and simple screening methods for the detection of SARS-CoV-2 are critically required to fight the current pandemic. In this work we present a proof of concept for, a simple optical sensing method for the screening of SARS-CoV-2 through its spike protein subunit S1. The method utilizes a target-specific extractor chip to bind the protein from the biological specimens. The disulfide bonds of the protein are then reduced into a biothiol with sulfhydryl (SH) groups that react with a blue-colored benzothiazole azo dye-Hg complex (BAN-Hg) and causes the spontaneous change of its blue color to pink which is observable by the naked eye. A linear relationship between the intensity of the pink color and the logarithm of reduced S1 protein concentration was found within the working range 130 ng.mL-1-1.3 pg mL-1. The lowest limit of detection (LOD) of the assay was 130 fg mL-1. A paper based optical sensor was fabricated by loading the BAN-Hg sensor onto filter paper and used to screen the S1 protein in spiked saliva and patients' nasopharyngeal swabs. The results obtained by the paper sensor corroborated with those obtained by qRT-PCR. The new paper-based sensing method can be extended to the screening of many viruses (e.g. the human immunodeficiency virus, the human polyomavirus, the human papilloma virus, the adeno associated viruses, the enteroviruses) through the cysteine residues of their capsid proteins. The new method has strong potential for screening viruses at pathology labs and in remote areas that lacks advanced scientific infrastructure. Further clinical studies are warranted to validate the new sensing method.