Evaluation of the relationship of cytokines concentrations tumor necrosis factor-alpha, interleukin-6, and C-reactive protein in obese diabetics and obese non-diabetics: A comparative study.

Obesity has been linked to a low-grade inflammatory process in the white adipose tissue. Our study aims to detect the relationship between cytokine levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) in obese diabetics, compared to obese non-diabetics, Iraqi individuals. Ninety Iraqi adults, 45 type 2 diabetic and 45 non-diabetic obese, were selected as controls. Serum levels of TNF-α, IL-6, CRP, homeostatic model assessment for homeostasis model assessment of insulin resistance (HOMA-IR), body fat, and body mass index (BMI) were measured. The concentration of TNF-α, IL-6, and CRP were significantly greater in the obese diabetics, compared to the obese non-diabetics. BMI was significantly positively correlated with the concentration of TNF-α, IL-6, and CRP in the two groups. At the same time, HOMA-IR was non-significantly positively associated with them in obese diabetics. In contrast, the correlation was significantly positive between HOMA-IR with TNF-a, IL-6, and CRP in the obese non-diabetics group. Obese diabetics have more inflammation than obese non-diabetics as evidenced by the former's higher levels of TNF-α and IL-6. Obesity-related imbalances disrupt metabolic processes and increase CRP, TNF-, and IL-6 levels. Therefore, IR is promoted by the increase of cytokines.

Apoferritin nanocages for targeted delivery of idarubicin against breast cancer cells.

In recent years, nanotechnology has attracted attention for its capability to diagnose and remedy diverse tumors successfully.  Protein nanocarriers as a platform of targeted drug delivery can be used to reduce toxicity and improve the effect of anticancer drugs. Idarubicin (IDR) is a chemotherapy drug that is classified as an anthracycline antitumor. In this study, IDR was encapsulated within horse spleen apoferritin (HsAFr) nanocarriers. Encapsulation was obtained through disassembling apoferritin into subunits at pH 2 and subsequently reassembling it at pH 7.4 in the presence of IDR. Transmission electron microscopy, UV-vis, and fluorescence spectroscopy techniques showed that drug molecules are loaded within apoferritin. Intrinsic fluorescence information exhibited that the encapsulation does not have any effects on the tertiary structure of the protein. Drug loading and entrapment efficiency were found to be 7.15% and 84.75%, respectively. Comparison of anticancer activities in HsAFr-IDR and free drug IDR was made via the MTT viability technique in a human breast cancer cell line (MCF-7).

A promising dual-drug targeted delivery system in cancer therapy: nanocomplexes of folate-apoferritin-conjugated cationic solid lipid nanoparticles.

Various nano-sized protein and lipid complexes are being investigated as drug delivery systems. The encapsulation of more than one drug in a single nanocomplex carrier could enhance the therapeutic potency and afford synergistic therapeutic effects. In this study, we developed a novel protein-lipid nanocomplex as a controlled drug delivery system for two important cancer drugs, doxorubicin (DOX) and mitoxantrone (MTO). Apoferritin (AFr) functionalized with folic acid (FA) was used to encapsulate DOX to create the targeted protein nanocomplexes (TPNs). The second drug, MTO, was loaded into the cationic solid lipid nanoparticles (cSLN) to form the liposomal drug nanocomplex particles (MTO-cSLNs). Two complexes were then assembled by tight coupling through ionic interactions to obtain the final drug delivery system, the dual-targeted protein-lipid nanocomplexes (DTPLNs). UV-Vis and fluorescence spectroscopy were used for structural characterization of TPNs and DTPLNs. Transmission electron microscopy (TEM) was used for comprehensive analysis of the final DTPLNs. We confirmed that the DTPLNs display desired time-dependent and pH-dependent drug release behaviors. We also demonstrated the improved anti-cancer efficacy of DOX and MTO in their encapsulated DTPLNs as compared to their free forms. Our results provide promising prospects for the application of the DTPLNs as efficient drug delivery systems.

New Folate-Modified Human Serum Albumin Conjugated to Cationic Lipid Carriers for Dual Targeting of Mitoxantrone against Breast Cancer.

AIMS: In the present work, folic acid-modified human serum albumin conjugated to cationic solid lipid nanoparticles were synthesized as nanocarriers of mitoxantrone for the treatment of breast cancer. BACKGROUND: Dual-targeted drug delivery is a new drug dosing strategy that is frequently used to enhance the therapeutic efficacy of anticancer drugs. OBJECTIVE: Dual targeting of the cancer cells was achieved by dual tagging of human serum albumin and folic acid on the surface of the lipid nanoparticles. METHODS: The targeted drug-loaded nanocomplexes were synthesized and characterized using transmission electron microscopy along with photon-correlation and Fourier-transform infrared spectroscopic techniques. The anti-cancer activity of the nanocomplexes was screened against an in-vitro model of MCF-7 and MDA-MB-231 breast cancer cell lines to examine drug efficacy. RESULTS: The entrapment efficiency and drug loading values for mitoxantrone were calculated to be 97 and 8.84%, respectively. The data from the drug release studies for the system indicated the release profile did not significantly change within a pH range of 5.5-7.4. The hemolysis ratio of the hybrid carrier was less than 5% even at the upper doses of 3 mg/mL, demonstrating its safety for intravenous injection with limited hemolysis and a long blood circulation time. CONCLUSION: The cell cytotoxicity results confirmed that the drug hybrid nanocomplex was more toxic to breast cancer cells compared with the free drug. Furthermore, the weakly cationic and small size particles prevented opsonin binding of nanocomplexes, improving blood circulation time and cancer tissue uptake.

Biosensor design using an electroactive label-based aptamer to detect bisphenol A in serum samples.

A new and simple procedure was applied to detect bisphenol A (BPA) based on a BPA aptamer and its complementary strand (Comp. Str.). An electrode was modified with a mixture of carboxylated multiwalled carbon nanotubes and chitosan. The Comp. Str. was immobilized on a modified-glassy carbon electrode (GCE) surface via covalent binding. After the incubation of the aptamer with the electrode surface, it could interact with the Comp. Str. In the presence of BPA, its aptamer will interact with the analyte, resulting in some changes in the configuration and leading to separation from the electrode surface. Due to the attached ferrocene (Fc) group on the 50 head of the aptamer, the redox current of Fc has reduced. This aptasensor can sense the level of BPA in the linear range of 0.2-2 nM, with a limit of detection of 0.38 nM and a sensitivity of 24.51 lA/µM. The proposed aptasensor showed great reliability and selectivity. The acceptable selectivity is due to the specificity of BPA binding to its aptamer. The serum sample was used as a real sample; the aptasensor was able to effectively recover the spiked BPA amounts. It can on-site monitor the BPA in serum samples with acceptable recoveries.

A Review on Targeting Nanoparticles for Breast Cancer.

Chemotherapeutic agents have been used extensively in breast cancer remedy. However, most anticancer drugs cannot differentiate between cancer cells and normal cells, leading to toxic side effects. Also, the resulted drug resistance during chemotherapy reduces treatment efficacy. The development of targeted drug delivery offers great promise in breast cancer treatment both in clinical applications and in pharmaceutical research. Conjugation of nanocarriers with targeting ligands is an effective therapeutic strategy to treat cancer diseases. In this review, we focus on active targeting methods for breast cancer cells through the use of chemical ligands such as antibodies, peptides, aptamers, vitamins, hormones, and carbohydrates. Also, this review covers all information related to these targeting ligands, such as their subtypes, advantages, disadvantages, chemical modification methods with nanoparticles and recent published studies (from 2015 to present). We have discussed 28 different targeting methods utilized for targeted drug delivery to breast cancer cells with different nanocarriers delivering anticancer drugs to the tumors. These different targeting methods give researchers in the field of drug delivery all the information and techniques they need to develop modern drug delivery systems.

Correction to: Immobilization of tyrosinase on Fe3o4@Au core-shell nanoparticles as bio-probe for detection of dopamine, phenol and catechol.

In the original article, the third author's name and affiliation is incorrectly published.

Development and characterization of folic acid-functionalized apoferritin as a delivery vehicle for epirubicin against MCF-7 breast cancer cells.

Epirubicin (Epr) is an effective chemotherapeutic drug; however, the clinical amenability of Epr is limited by its highly toxic interaction with normal cells. This toxicity can be decreased by utilizing nanocarriers and targeted drug delivery systems. This work describes an approach for the delivery of Epr via encapsulation in the horse spleen apoferritin (HsAFr) cavity. The encapsulation was achieved by the disassembling of apoferritin into subunits at pH 2 followed by its reformation at pH 7.4 in the presence of Epr. The surface of HsAFr-encapsulated Epr was modified with folic acid (FA) for optimal targeting of breast cancer cells (MCF-7). The use of FA to functionalize HsAFr could enhance the cellular uptake efficiency via FA-receptor-mediated endocytosis. UV-vis spectroscopy, fluorescence spectroscopy, circular dichroism (CD) and transmission electron microscopy (TEM) were utilized for structural characterization of the HsAFr-Epr and HsAFr-Epr-FA complexes. The comparison of the anti-cancer activities across the HsAFr-Epr-FA complex and the free Epr drug was performed using the MTT viability assay on MCF-7.

Apoferritin-templated biosynthesis of manganese nanoparticles and investigation of direct electron transfer of MnNPs-HsAFr at modified glassy carbon electrode.

Manganese nanoparticles (MnNPs) were created within horse spleen apoferritin (HsAFr) cavity nanotemplates. Transmission electron microscopy revealed the particle size to be 6 nm. Intrinsic fluorescence data showed that the mineralization acted as a quencher of the HsAFr fluorescence, and extrinsic fluorescence data revealed that the hydrophobic binding site at the surface of HsAFr was not changed. Finally, the MnNP-HsAFr was immobilized onto multiwalled carbon nanotubes entrapped into chitosan (CS) matrices by through sequential 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide-N-hydroxysuccinimide and glutaraldehyde coupling. The MnNPs-HsAFr immobilized on CNT-CS/GC electrode was characterized by cyclic voltammetry. This charge transfer coefficient (α) and the exchange current (i0 ) of MnNPs-HsAFr immobilized on modified electrode in 0.1 M phosphate solution (pH 7.5) were found to be 0.57 and 0.48 µA, respectively.

An electrochemical biosensor based on cobalt nanoparticles synthesized in iron storage protein molecules to determine ascorbic acid.

The electrochemical detection of ascorbic acid (AA) was investigated using a cobalt(III)-ferritin immobilized on a self-assembled monolayer modified gold electrode in phosphate buffer solution (pH 7.5). The modified electrode showed excellent electrochemical activity for oxidation of AA. The response to AA on the modified electrode was examined using cyclic and differential pulse voltammetry techniques. The resulting biosensor showed a linear response to AA in a concentration range from 6.25×10-6 to 2.31×10-5 M with sensitivity of 86,437 µAM-1 and detection limit of 4.65 × 10-6 M based on a signal-to-noise ratio of 3. Electrochemical parameters including the charge transfer coefficient (α) and the apparent heterogeneous electron transfer rate constant (ks ) for AA were found to be 0.52 and 1.054 Sec-1 , respectively. It has been shown that, using this modified electrode, AA can be determined with high sensitivity, low detection limit, and high selectivity.

Laccase immobilization on the electrode surface to design a biosensor for the detection of phenolic compound such as catechol.

Biosensors based on the coupling of a biological entity with a suitable transducer offer an effective route to detect phenolic compounds. Phenol and phenolic compounds are among the most toxic environmental pollutants. Laccases are multi-copper oxidases that can oxide phenol and phenolic compounds. A method is described for construction of an electrochemical biosensor to detect phenolic compounds based on covalent immobilization of laccase (Lac) onto polyaniline (PANI) electrodeposited onto a glassy carbon (GC) electrode via glutaraldehyde coupling. The modified electrode was characterized by voltammetry, Fourier transform infrared (FTIR) spectroscopy and atomic force microscopy (AFM) techniques. The results indicated that laccase was immobilized onto modified GC electrode by the covalent interaction between laccase and terminal functional groups of the glutaraldehyde. The laccase immobilized modified electrode showed a direct electron transfer reaction between laccase and the electrode. Linear range, sensitivity, and detection limit for this biosensor were 3.2 × 10(-6) to 19.6 × 10(-6)M, 706.7 mAL mol(-1), 2.07 × 10(-6)M, respectively.

Sensitive electrochemical biosensing of H2O2 based on cobalt nanoparticles synthesised in iron storage protein molecules, ferritin.

In this report, a highly sensitive electrochemical biosensor based on cobaltferritin immobilised on a self-assembled monolayer modified gold electrode for determination of hydrogen peroxide (H2O2) in phosphate buffer solution (pH 7.5) was investigated. The modified electrode showed excellent electrochemical activity for oxidation of H2O2. The response to H2O2 on the modified electrode was examined using linear sweep and differential pulse voltammetries. In phosphate buffer (pH 7.5, 0.1 M), the fabricated biosensor exhibited a linear dependence (R = 0.989) on the concentration of H2O2 from 2.49 × 10(-9) to 1.91 × 10(-8) M, a high sensitivity of -0.4099 µA/nM and detection limit of 2.48 × 10(-9) based on a signal-to-noise ratio of 3. Charge transfer coefficient (α) and the exchange current (i0) of oxidation for H2O2 were found to be 0.57 and 7.55 A, respectively. It has been shown that, this modified electrode is able to determine H2O2 with a high sensitivity, low detection limit and high selectivity.

Biomimetic synthesis and characterization of cobalt nanoparticles using apoferritin, and investigation of direct electron transfer of Co(NPs)-ferritin at modified glassy carbon electrode to design a novel nanobiosensor.

Oxyhydroxy cobalt CoO(OH) nanoparticles (Co-NPs) were prepared in horse spleen apoferritin (HsAFr) cavity. Transmission electron microscopy revealed the particle size was 5.5-6 nm. Mineralization effect on HsAFr was investigated by fluorescence and far-UV circular dichroism (far-UV CD) spectroscopies. The far-UV CD experiments indicated an increase in the α-helical content after mineralization. Intrinsic fluorescence data showed that mineralization acts as a quencher of HsAFr. For the first time, direct electron transfer between Co(NPs)-HsAFr and a glassy carbon electrode in the thin film of dihexadecylphosphate (DHP) was investigated by cyclic voltammetry (CV) to design a biosensor. The anionic surfactant DHP was used to achieve direct electron-transfer between Co(NPs)-HsAFr molecules and the GC electrode surface. CV result showed clearly a pair of well-defined and quasi-reversible redox peaks arise from Co(NPs)-HsAFr embedded in DHP film. This novel biosensor can be used in medical and industrial fields to detect different analytes.