Development of New Nanoniosome Carriers for Vorinostat: Evaluation of Anticancer Efficacy In Vitro.

Vorinostat (VST) is a chemotherapeutic agent administrated for various types of cancers. However, it suffers from side effects and chemoresistance that reduce its application. Different nanoniosomes comprised Span 20, 60, 65 and 80 were prepared by the thin film hydration method and loaded with VST. The nanoniosomes were physicochemically characterized using particle size analysis and field emission scanning electron microscopy. The best formulation that was prepared using Span 65 (VST-NN-S65) included vesicle size of 127 nm with a narrow size distribution. VST-NN-S65 had an entrapment efficiency and loading capacity of 81.3 ± 5.1 and 32.0 ± 3.9 %, respectively. Drug release rate measurements showed that 90 % of VST was liberated within 1 h. Cytotoxicity assessments of VST-NN-S65 in HeLa and MCF7 cells indicated significant improvement in the effectiveness of VST, compared to the VST suspension. For VST-NN-S65, IC50 values of 26.3 and 6.6 µg mL-1 were obtained for HeLa and MCF7 cell lines, respectively. In situ apoptosis detection by the TUNEL assay revealed that apoptosis mainly occurred in the cell lines.

Evaluating the Long-Term Outcomes of Periodontal Surgery vs. Non-Surgical Treatment in Aggressive Periodontitis.

Background: Aggressive periodontitis is a severe form of periodontal disease characterized by rapid tissue destruction and tooth loss. The optimal treatment approach for managing this condition remains a topic of debate. Materials and Methods: A retrospective cohort study was conducted, involving patients diagnosed with aggressive periodontitis who received either surgical or non-surgical treatment between 2010 and 2020. Clinical and radiographic data were collected at baseline and regular intervals over a 5-year follow-up period. Surgical interventions included flap surgery, guided tissue regeneration, and bone grafting, while non-surgical treatments comprised scaling and root planning with or without adjunctive antibiotics. The primary outcomes assessed included changes in probing depth, clinical attachment level, tooth loss, and patient-reported quality of life measures. Results: A total of 120 patients were included in the study, with 60 patients in each treatment group. The surgical group demonstrated significantly greater reductions in probing depth and gains in clinical attachment level compared to the non-surgical group (P < 0.05). Tooth loss was significantly lower in the surgical group over the 5 years (P < 0.01). Patient-reported outcomes also favored the surgical group, with improved oral health-related quality of life. However, the surgical group had a higher incidence of postoperative complications. Conclusion: This study suggests that periodontal surgery yields superior long-term outcomes in the management of aggressive periodontitis compared to non-surgical treatment.

An amplified sonodynamic therapy by a nanohybrid of titanium dioxide-gold-polyethylene glycol-curcumin: HeLa cancer cells treatment in 2D monolayer and 3D spheroid models.

The utilization of ultrasound (US) to activate sonosensitizers for sonodynamic therapy (SDT) has faced challenges such as low activation efficiency and limited therapeutic outcomes, which have hampered its clinical applications. In this study, a nanohybrid of titanium dioxide-gold-polyethylene glycol-curcumin (TiO2-Au-PEG-Cur NH), as a novel US sensitizer, was synthesized, characterized, and applied for SDT of HeLa cancer cells in 2D monolayer model, and also a 3D spheroid model to bridge the gap between 2D cell culture and in vivo future studies. TiO2-Au-PEG-Cur NH contained TiO2 nanoparticles of 36 ± 11 nm in diameter, PEG-curcumin as a filler, and gold nanoparticles of 21 ± 7 nm in diameter with a high purity and a 35:17 of Ti:Au ratio (W/W), and it had a band gap of 2.4 eV, a zeta potential of -23 ± 7 mV, high stability upon US radiation cycles as well as one year storage. SDT of HeLa cells using TiO2-Au-PEG-Cur NH was investigated in the courses of cytotoxicity assessment in vitro, reactive oxygen species (ROS) generation capability, colony formation, cell migration, and the way to form spheroid. IC50 values of 122 and 38 µg mL-1 were obtained for TiO2-Au-PEG-Cur NH without and with US radiation, respectively. TiO2-Au-PEG-Cur NH not only exhibited an inherent capacity to generate ROS, but also represented an excellent therapeutic performance on the cancer cells through ROS generation and enhanced inhibitory effects on cell migration and spheroid formation.

An impedimetric genosensor for Leishmania infantum based on electrodeposited cadmium sulfide nanosheets.

It is estimated that there are 400000 new cases of visceral leishmaniasis each year, with about 30,000 deaths. Therefore, detection of this pathogen and its species is highly vital for overall health of the community. In the present research, a DNA-based biosensor, namely genosensor, was introduced for detection of genomic DNA of Leishmania infantum. The genosensor was fabricated based on the transduction of cadmium sulfide nanosheets and recognition of a particular single stranded DNA sequence, and worked in label-, marker-, tag- and PCR-free manners. Impedimetric measurements were performed in a wide range of frequency (recording Nyquist diagrams) without applying external force (working at open circuit potential) upon hybridization of DNA targets with the cadmium sulfide nanosheets surface-immobilized probe. The genosensor detected the complementary DNA strand in a concentration range of 1.0 × 10-14 to 1.0 × 10-6 mol L-1 and a detection limit (DL) of 0.81 fmol L-1 (6.5 fg mL-1), and genomic DNA of Leishmania infantum in a concentration range of 5-50 ng µL-1 and a DL of 1.2 ng µL-1. The genosensor had a very good selectivity, fabrication reproducibility and stability, and was applicable for practical applications.

Advances in prostate specific antigen biosensors-impact of nanotechnology.

Prostate cancer is one of the most dangerous and deadly cancers in elderly men. Early diagnosis using prostate-specific antigen (PSA) facilitates disease detection, management and treatment. Biosensors have recently been used as sensitive, selective, inexpensive and rapid diagnostic tools for PSA detection. In this review, a variety of PSA biosensors such as aptasensors, peptisensors and immunesensors are highlighted. These use aptamers, peptides and antibodies in the biorecognition element, respectively, and can detect PSA with very high sensitivity via electrochemical, electrochemiluminescence, fluorescence and surface-enhanced Raman spectroscopy. To improve the sensitivity of most of these PSA biosensors, different nanostructured materials have played a critical role.

An electrochemical signal-on apta-cyto-sensor for quantitation of circulating human MDA-MB-231 breast cancer cells by transduction of electro-deposited non-spherical nanoparticles of gold.

A highly simple, sensitive, specific and low-cost electrochemical apta-cyto-sensor for determination of circulating human MDA-MB-231 breast cancer cells was fabricated. Non-spherical nanoparticles of gold were electro-deposited in the presence of ethosuximide as a shape directing and size controlling agent. The nanoparticles had dimensions ranging 50-150 nm, and covered the underlying surface with a roughness factor of 8.03. The Non-spherical nanoparticles were then employed as the apta-cyto-sensor transducer. A 83-mer DNA aptamer that is specific to capturing the cell surface proteins was immobilized on the transducer surface, and binding with the cells was followed using the ferro/ferricyanide redox marker. The aptamer was immobilized within ∼200 min on the transducer surface. The cells were quantified with an equation of regression of ΔIp(µA) = (1.028 ±â€¯0.027) log (C (cell mL-1)) + (0.2199 ±â€¯0.0944), a sensitivity of 1.028 µA (log (concentration / cell mL-1))-1 and a quantitation limit of 2 cell mL-1, in a concentration range of 5 to 2 × 106 cell mL-1. The apta-cyto-sensor selectivity was also evaluated toward AsPC-1, Calu-6, HeLa, MCF-7 and melanoma B16/F10 cell lines. The apta-cyto-sensor had a fabrication reproducibility of 4.2%, regeneration capability of 5.1%, a stability of 35 days, and a potential application for the detection of MDA-MB-231 cells in the spiked blood serum samples with a sensitivity of 0.8975 µA (log (concentration / cell mL-1))-1 and a quantitation limit of 5 cell mL-1, in a concentration range of 10 to 1 × 103 cell mL-1. The apta-cyto-sensor would be applicable for breast cancer diagnosis at early stage.

Capecitabine-loaded nanoniosomes and evaluation of anticancer efficacy.

Capecitabine (CAP) is an FDA-approved and frequently used chemotherapeutic agent for the treatment of various cancers. However, there are some side effects and chemoresistance limiting its use. Nanotechnological approaches can enhance the efficacy of anticancer drugs. In this study, CAP-loaded nanoniosomes were prepared. Nanoniosomes were prepared by the method of thin film hydration wherein CAP was loaded into the nanoniosomes. Nanoniosomes were then characterized by field emission scanning electron microscopy and (particle) vesicle size analysis. The cytotoxicity effect of the nanoniosomes were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. CAP was loaded into the nanoniosomes and loading capacity and entrapment efficiency were determined. The vesicle size of the nanoniosomes was obtained in the nanometer scale, and CAP release profiles from the nanoniosomes were also obtained. Finally, the cytotoxicity effect of CAP and CAP-loaded nanoniosomes were evaluated toward MCF7 and PANC1 cell lines. The nanoniosomes with an amphipathic structure can penetrate into the cells with an enhanced release rate. These caused the toxicity of drug in the nanoniosomes to be higher than the free drug.

A molecularly imprinted electrochemical nanobiosensor for prostate specific antigen determination.

Prostate Specific Antigen (PSA) is a biomarker employed for detection of prostate cancer. An electrochemical nanobiosensor is designed and fabricated using a molecularly imprinted polymer for the simple and fast PSA detection. The imprinted polymer served as a PSA artificial receptor fabricated by electrochemical polymerization of pyrrole on screen-printed gold electrode in the presence of PSA. PSA was a molecular template for the polymer. The fabricated nanobiosensor was evaluated by differential pulse voltammetry and using K3[Fe(CN)6]/K4[Fe(CN)6] as an electrochemical marker. The factors influencing the performance of the sensor including electropolymerization cycle umbers (to control the thickness of the polymer film) and time of PSA binding were optimized to attain the best sensitivity. The binding affinity of the nanobiosensor surface was examined by the Freundlich isotherm with Freundlich constant and exponent of 0.89 ng mL-1 and 10.93, respectively. The nanobiosensor demonstrated a fast rebinding rate and a high capacity of PSA recognition with detection limit of 2.0 pg mL-1.

Evaluation of a self-nanoemulsifying docetaxel delivery system.

A self-nanoemulsifying drug delivery system (SNEDDS) was developed as a novel route to enhance the efficacy of docetaxel lipophilic drug. SNEDDS comprised ethyl oleate, Tween 80 and poly(ethylene glycol) 600, as oil, surfactant and co-surfactant, and formed stabilized monodispersed oil nanodroplets upon dilution in water. SNEDDS represented encapsulation efficiency and loading capacity of 21.4 and 52.7%, respectively. The docetaxel release profile from the drug-loaded SNEDDS was recorded, its effectiveness against MCF-7 cell line was investigated, and an IC50 value of 0.98 ± 0.05 µg mL-1 was attained. The drug-loaded SNEDDS was administrated in rats, and the pharmacokinetic parameters of maximum concentration of 22.2 ± 0.8 µg mL-1, time to attain this maximum concentration of 230 min, and area under the curve of 1.71 ± 0.18 µg min mL-1 were obtained. The developed SNEDDS formulation can be represented as an alternative to docetaxel administration.

A novel self-nanoemulsifying formulation for sunitinib: Evaluation of anticancer efficacy.

Breast cancer is the top cancer and a main cause of death among women. The incidence of this cancer is increasing in the world. Sunitinib maleate is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor that inhibits tumor cell proliferation and angiogenesis, and has been administrated as an anticancer drug. Self-nanoemulsifying drug delivery system (SNEDDS) is an isotopic mixture of an oil, a surfactant and usually a co-surfactant, which can spontaneously form fine oil-in-water nanoemulsion in aqueous media. Here, a SNEDDS composed of 15% ethyl oleate (as an oil phase), 30% tween 80 (as a surfactant), and 55% PEG 600 (as a co-surfactant) was prepared and developed as a carrier for sunitinib. The average droplet size of sunitinib-loaded SNEDDS was 29.5±6.3nm with a stability of more than one month. Sunitinib release from SNEDDS was enhanced accompanied by a controlled dissolution of the drug. Cytotoxicity studies on 4T1 and MCF-7 cell lines indicated a toxicity enhancement in sunitinib by SNEDDS. To inspect the bioavailability of the drug-loaded SNEDDS after oral administration with a dose of 50mgkg-1, the maximum plasma concentration and the mean area under the plasma concentration-time curve were measured. It was found that these parameters were increased 1.45- and 1.24-times respectively, compared to a drug suspension.

Erlotinib-loaded albumin nanoparticles: A novel injectable form of erlotinib and its in vivo efficacy against pancreatic adenocarcinoma ASPC-1 and PANC-1 cell lines.

Erlotinib was loaded on albumin nanoparticles for the first time and the cytotoxic effect of the resulting nanoparticles against ASPC-1 and PANC-1 pancreatic adenocarcinoma cell lines was evaluated. The carrier (albumin nanoparticles, ANPs) was synthesized by desolvation method using a mixed solvent followed by thermal crosslinking for stabilization. ANPs and the drug-loaded ANPs were characterized by field emission scanning and transmission electron microscopies, particle size analysis and Fourier transform infrared spectroscopy. The nanoformulation had a size of <14nm with a good monodispersity. Drug loading and encapsulation efficiencies were evaluated as 27 and 44%. Cytotoxicity assays after 72h revealed the potential of ANPs to improve erlotinib toxicity (54% against 34% of free drug toward ASPC-1 cell line, and 52% against 30% toward PANC-1 cell line). Values of IC50 were obtained for both cell lines and indicated significant reduction in the erlotinib dose necessary for killing the cells, while, ANPs were completely safe. The results demonstrated that erlotinib-loaded ANPs had a remarkable potential for pancreatic cancer drug delivery.

Label-free electrochemical aptasensing of the human prostate-specific antigen using gold nanospears.

Gold nanospears were electrodeposited with the assistance of arginine as a soft template and precise selection of experimental parameters. The nanospears were then employed as a transducer to immobilize an aptamer of prostate-specific antigen (PSA) and fabrication of a label-free electrochemical aptasensor. The aptasensor was employed for the detection of PSA with a linear concentration range of 0.125-200ngmL(-1) and a limit of detection of 50pgmL(-1). The aptasensor was successfully applied to detect PSA in blood serum samples of healthy and patient persons.

Photothermal cancer therapy by gold-ferrite nanocomposite and near-infrared laser in animal model.

Surface plasmon resonance effect of gold nanostructures makes them good candidates for photothermal therapy (PTT) application. Herein, gold-ferrite nanocomposite (GFNC) was synthesized and characterized as a photothermal agent in PTT. The aim of this study was to investigate the effect of GFNC upon laser irradiation on treatment of cancer in mice bearing melanoma cancer. Thirty mice received 1.5 × 10(6) B16/F10 cells subcutaneously. After 1 week, the mice bearing solid tumor were divided into four groups: control group (without any treatment), laser group (received laser irradiation without GFNC injection), GFNC group (only received intratumorally GFNC), and GFNC + laser group (received intratumorally GFNC upon laser irradiation). In GFNC + laser group, 200 µL of fluid, 1.3 × 10(-7) mol L(-1) gold nanoparticles, was injected intratumorally and immediately the site of tumor was exposed to continuous wave diode laser beam (808 nm, 1.6 W cm(-2)) for 15 min. All mice but four were euthanized 24 h after treatment to compare the necrotic surface area histologically by using measuring graticule. Statistical analyses revealed significant differences in necrosis extent for GFNC + laser group, compared to other groups. Four subjects (control group and GFNC + laser group, two mice each) were kept for longitudinal study. Histological analyses and tumor volume measurements of the four subjects indicated that tumor in GFNC + laser group was controlled appropriately. It was concluded that combining an 808-nm laser at a power density of 1.6 W cm(-2) with GFNC has a destruction effect in melanoma cancer cells in an animal model.

Dextrin-coated zinc substituted cobalt-ferrite nanoparticles as an MRI contrast agent: In vitro and in vivo imaging studies.

Application of superparamagnetic iron oxide nanoparticles (NPs) as a negative contrast agent in magnetic resonance imaging (MRI) has been of widespread interest. These particles can enhance contrast of images by altering the relaxation times of the water protons. In this study, dextrin-coated zinc substituted cobalt-ferrite (Zn0.5Co0.5Fe2O4) NPs were synthesized by a co-precipitation method, and the morphology, size, structure and magnetic properties of the NPs were investigated. These NPs had superparamagnetic behavior with an average size of 3.9 (±0.9, n=200)nm measured by transmission electron microscopy. Measurements on the relaxivities (r2 and r2(*)) of the NPs were performed in vitro by agarose phantom. In addition, after subcutaneous injection of the NPs into C540 cell line in C-57 inbred mice, the relaxivities were measured in vivo by a 1.5T MRI system. These NPs could effectively increase the image contrast in both T2-and T2(*)-weighted samples.

A study of double stranded DNA adsorption on aluminum surface by means of electrochemical impedance spectroscopy.

Immobilization of DNA on the solid surfaces is one of the goals in bio- and nano-technologies. Adsorption of double stranded DNA on the surface of aluminum was electrochemically studied by means of impedance spectroscopy. Nyquist diagram of aluminum in a tris (hydroxymethyl) ammoniummethane-HCl (Tris-HCl) buffer solution, pH 7.4 consisted of two overlapped capacitive semicircles. The high-frequency semicircle was related to the passivity of Cl(-)-containing aluminum species in the oxide layer, and low-frequency semicircle was attributed to metal dissolution. When DNA was added to the Tris-HCl buffer solution, Nyquist diagrams represented an inductive loop at low frequencies due to the adsorption of DNA on the pre-covered aluminum surface by hydroxy-contained species. The DNA adsorption on the aluminum surface was also confirmed by X-ray photoelectron spectroscopy. Open circuit potential variation with time also indicated the chemical adsorption of DNA on the aluminum surface.

A flower-like nickel oxide nanostructure: synthesis and application for choline sensing.

Flower-like nickel oxide nanostructure was synthesized by a simple desolvation method. The nanostructure was then employed as the modifier of a carbon paste electrode to fabricate a choline sensor. The mechanism and kinetics of the electrocatalytic oxidation of choline on the modified electrode surface were studied by cyclic voltammetry, steady-state polarization curve, and chronoamperometry. The catalytic rate constant and the charge transfer coefficient of the choline electrooxidation process by an active nickel species, and the diffusion coefficient of choline were reported. An amperometric method was developed for determination of choline with a sensitivity of 60.5 mA mol(-1)Lcm(-2) and a limit of detection of 25.4 µmol L(-1). The sensor had the advantages of high electrocatalytic activity and sensitivity, and long-term stability toward choline, with a simple fabrication method without complications of immobilization steps and using any enzyme or reagent.

An electrochemical acetylcholine sensor based on lichen-like nickel oxide nanostructure.

Lichen-like nickel oxide nanostructure was synthesized by a simple method and characterized. The nanostructure was then applied to modify a carbon paste electrode and for the fabrication of a sensor, and the electrocatalytic oxidation of acetylcholine (ACh) on the modified electrode was investigated. The electrocatalytic efficiency of the nickel oxide nanostructure was compared with nickel micro- and nanoparticles, and the lichen-like nickel oxide nanostructure showed the highest efficiency. The mechanism and kinetics of the electrooxidation process were investigated by cyclic voltammetry, steady-state polarization curve and chronoamperometry. The catalytic rate constant and the charge transfer coefficient of ACh electrooxidation by the active nickel species, and the diffusion coefficient of ACh were reported. A sensitive and time-saving hydrodynamic amperometry method was developed for the determination of ACh. ACh was determined with a sensitivity of 392.4 mA M⁻¹ cm⁻² and a limit of detection of 26.7 µM. The sensor had the advantages of simple fabrication method without using any enzyme or reagent and immobilization step, high electrocatalytic activity, very high sensitivity, long-term stability, and antifouling surface property toward ACh and its oxidation product.

An electrocatalytic transducer for L-cysteine detection based on cobalt hexacyanoferrate nanoparticles with a core-shell structure.

The electrocatalytic oxidation of L-cysteine (CySH) was studied on cobalt hexacyanoferrate nanoparticles with a core-shell structure (iron(III) oxide core-cobalt hexacyanoferrate shell) using cyclic voltammetry and chronoamperometry. Voltammetric studies represented two quasi-reversible redox transitions for the nanoparticles in phosphate buffer solution (pH 7.4). In the presence of CySH, the anodic peak current of the Fe(II)/Fe(III) transition was increased, followed by a decrease in the corresponding cathodic peak current, whereas the peak currents related to the Co(II)/Co(III) transition almost remained unchanged. The results indicated that the nanoparticles oxidized CySH via a surface mediation electrocatalytic mechanism. The catalytic rate constant, the electron transfer coefficient, and the diffusion coefficient involved in the electrooxidation process of CySH are reported here. Ultrasensitive and time-saving determination procedures were developed for the analysis of the CySH, and the corresponding analytical parameters are reported. According to the proposed methods, CySH was determined with detection limits of 40 and 20 nm in batch and flow systems, respectively. The proposed amperometric method was also applied to the analysis of CySH in human urine and serum blood samples.

Nickel oxide nanotubes-carbon microparticles/Nafion nanocomposite for the electrooxidation and sensitive detection of metformin.

The electrocatalytic oxidation of metformin was studied on a nickel oxide nanotubes-carbon microparticles/Nafion nanocomposite, using cyclic voltammetry and chronoamperometry. In the presence of metformin, the anodic peak current of the Ni(II)/Ni(III) transition increased, followed by a decrease in the corresponding cathodic currents. Based on the results, the drug was oxidized on nickel oxide nanotubes via an electrocatalytic mechanism. The catalytic rate constant, the electron transfer coefficient and the diffusion coefficient involved in the electrocatalytic oxidation of the drug were reported. A sensitive and efficient amperometric method was presented for the analysis of the drug, and the corresponding analytical parameters were reported. For metformin, a detection limit of 0.45 micromol L(-1) was obtained. The proposed amperometric method was also applied to the analysis of commercial tablets and the results were in good agreement with the declared values. Also, the applicability of the method to the direct assays of the drug in human serum and urine and breast milk was described.

An electrochemical acetylcholine biosensor based on nanoshells of hollow nickel microspheres-carbon microparticles-Nafion nanocomposite.

Electrocatalytic oxidation of acetylcholine (ACh) on different nickel-based composites was investigated. Cyclic voltammetry, steady-state polarization measurements and chronoamperometry were employed to study the mechanism and kinetics of the oxidation process. The results showed that ACh was irreversibly oxidized on nickel nanoshells-carbon microparticles-Nafion nanocomposite with an excellent catalytic activity. The catalytic rate constant and the transfer coefficient for the electrocatalytic oxidation of ACh and the diffusion coefficient of ACh were obtained using cyclic voltammetry, steady-state polarization measurements and chronoamperometry. A sensitive and time-saving hydrodynamic amperometry method was developed for the determination of ACh. The nanocomposite showed a high sensing performance with a sensitivity of 48.58+/-0.52 mAM(-1)cm(-2) and a limit of detection of 49.33 nM. The nanocomposite represented many advantages as an ACh biosensor such as simple preparation method without using any specific enzyme or reagent, excellent catalytic activity, high sensitivity, long-term stability, and antifouling property toward ACh and its oxidation product(s). Sensitivity and detection limit of the present biosensor are better than all of the reports appeared in the literature.