Carbon-based aerogels for biomedical sensing: Advances toward designing the ideal sensor.

Carbon based aerogels are special solid-state materials comprised of interconnected networks of 3D nanostructures with high amount of air-filled nanoporous. They expand the structural properties along with physicochemical characteristics of nanoscale construction blocks to macroscale, and incorporate distinctive attributes of aerogels, like large surface area, high porosity, and low density, with particular features of the different constituents. These features impart aerogels with rapid response signal, high selectivity, and ultra-sensitivity for sensing diverse targets in biomedical media. This has prompted researchers to develop a variety of aerogel-based sensors with encouraging achievements. Hence, this work outlines sensing applications of aerogel-based sensors with a comprehensive overview on the carbon aerogel hybrid materials and their analytical performances. Authors tried to list advantages and limitations of the developed approach and introduced more potent research for possible devices designing. We also point out some challenges and future perspectives related to the improvement of high-efficiency aerogel-based sensors.

Kinetic and thermodynamic study of c-Met interaction with single chain fragment variable (scFv) antibodies using phage based surface plasmon resonance.

Mesenchymal epithelial transition factor (c-Met) has been recently regarded as an attractive target for the treatment of cancer. Our previous study showed that c-Met-specific single chain fragment variables (scFvs) can be considered as a promising therapy for cancer, however, their molecular interaction with c-Met protein have not been assessed. Accordingly, in the current study we aim to evaluate the kinetic and thermodynamic properties of c-Met interaction with these scFvs as anticancer agents by means of surface plasmon resonance (SPR) technique. Phage-scFvs were immobilized on the 11-mercaptoundecanoic acid gold chips after carboxylic groups activation by N-ethyl-N-(3-diethylaminopropyl) carbodiimide/N-hydroxysuccinimide and, then the c-Met binding to each scFvs (ES1, ES2, and ES3) at different concentrations (ranging from 20 to 665 µM) was explored. Kinetic studies revealed that ES1 has the highest affinity (KD = 3.36 × 10-8) toward its target at 25°C. Calculation of thermodynamic parameters also showed positive values for enthalpy and entropy changes, which was representative of hydrophobic forces between c-Met and ES1. Furthermore, the positive value of Gibbs free energy indicated that c-Met binding to ES1 was enthalpy-driven. Taken together, we concluded that produced ES1 can be applied as promising scFv-based therapy for diagnosis or targeting of c-Met in various cancers.

PAMAM Dendrimers as a Delivery System for Small Interfering RNA.

Polyamidoamine dendrimers (PAMAM) form positively charged nanoparticles that function as nonviral delivery vectors for gene therapy. They protect nucleic acids from enzymatic degradation and facilitate endocytosis and endosomal escape. In this chapter, we describe the preparation and in vitro evaluation of small interfering RNA (siRNA)-PAMAM dendrimers. The physicochemical properties of the designed formulations were evaluated by size and zeta potential assessment and atomic force microscopy (AFM). The binding and release of the siRNA molecules from the PAMAM dendrimers were also assessed. Visualization and quantitative analysis of the siRNA-PAMAM dendrimers in live cells were analyzed by fluorescence microscopy and flow cytometry, respectively. Improving siRNA delivery to human cells through PAMAM dendrimers should accelerate the clinical applications of RNA interference.

Application of various optical and electrochemical aptasensors for detection of human prostate specific antigen: A review.

Early stage detection of prostate cancer, one of the main causes of mortality among men, is of great importance for better treatment of the patients. Prostate specific antigen (PSA) is a glycoprotein which has been considered as the most potential serological biomarker for the detection of prostate cancer. Among the various techniques employed for PSA detection, aptamer-based biosensors (aptasensors) have achieved notable attention because of their unique features and great potentials as diagnostic tools. A variety of strategies such as integration of nanomaterials (NMs) into the structure of aptasensors have also been applied for enhancing the sensitivity of PSA detection. This article reviews recent advances in various optical and electrochemical aptasensors used for PSA detection.

PAMAM dendrimers as efficient drug and gene delivery nanosystems for cancer therapy.

Drug delivery systems for cancer chemotherapy are employed to improve the effectiveness and decrease the side-effects of highly toxic drugs. Most chemotherapy agents have indiscriminate cytotoxicity that affects normal, as well as cancer cells. To overcome these problems, new more efficient nanosystems for drug delivery are increasingly being investigated. Polyamidoamine (PAMAM) dendrimers are an example of a versatile and reproducible type of nanocarrier that can be loaded with drugs, and modified by attaching target-specific ligands that recognize receptors that are over-expressed on cancer cells. PAMAM dendrimers with a high density of cationic charges display electrostatic interactions with nucleic acids (DNA, siRNA, miRNA, etc.), creating dendriplexes that can preserve the nucleic acids from degradation. Dendrimers are prepared by conducting several successive "generations" of synthetic reactions so their size can be easily controlled and they have good uniformity. Dendrimers are particularly well-suited to co-delivery applications (simultaneous delivery of drugs and/or genes). In the current review, we discuss dendrimer-based targeted delivery of drugs/genes and co-delivery systems mainly for cancer therapy.

Kinetic and thermodynamic study of bovine serum albumin interaction with rifampicin using surface plasmon resonance and molecular docking methods.

The interaction of bovine serum albumin (BSA) with various drugs, such as antibiotics, due to the importance of BSA in drug delivery has attracted increasing research attention at present. Therefore, the aim of this study was investigation of BSA interaction with rifampicin using surface plasmon resonance (SPR) and molecular docking methods under the imitated physiological conditions ( pH = 7.4 ). BSA immobilization on carboxymethyl dextran hydrogel chip has been carried out after activation with N-hydroxysuccinimide/N-ethyl-N-(3-diethylaminopropyl) carbodiimide. The dose-response sensorgrams of BSA upon increasing concentration of refampicin were attained in SPR analysis. The high affinity of rifampicin to BSA was demonstrated by a low equilibrium constants ( K D ) value ( 3.46 × 10 ? 5 at 40°C). The process of kinetic values changing shows that affinity of BSA to rifampicin decreased with rising temperature. The positive value of both enthalpy change ( ? H ) and entropy change ( ? S ) showed that hydrophobic force plays major role in the BSA interaction with rifampicin. The positive value of ? G was indicative of nonspontaneous and enthalpy-driven binding process. In addition, according to the molecular docking study, hydrogen binding has some contributions in the interaction of rifampicin with BSA.

Formulation, characterization, and geno/cytotoxicity studies of galbanic acid-loaded solid lipid nanoparticles.

CONTEXT: Galbanic acid (GBA) is a sesquiterpene coumarin with different medicinal properties and anticancer effects. OBJECTIVE: To improve the anticancer activities of GBA, in the current study, we aimed to fabricate GBA-loaded solid lipid nanoparticles (GBA-SLNs) and study their biological activities in vitro. MATERIALS AND METHODS: Hot homogenization was used for preparation of GBA-SLNs. The encapsulation efficiency (EE) and drug loading (DL) and in vitro release were determined. MTT, DAPI, DNA fragmentation, comet, and Anexin V apoptosis assays were used to compare the anti-cell proliferation and genotoxicity properties of GBA and GBA-SLNs against A549 cells and HUVEC to detect apoptosis and DNA damage in the final concentration of 100 µM after 48 h treatment. RESULTS: Scanning electron microscopy (SEM) and particle size analysis showed spherical SLNs (92 nm), monodispersed distribution, and zeta potential of -23.39 mV. High EE (>98%) and long-term in vitro release were achieved. The stability of GBA-SLNs in aqueous medium was approved after 3 months in terms of size and polydispersity index. GBA was able to inhibit A549 growth with an IC50 value of 62 µM at 48 h. Although GBA-SLNs could also inhibit the growth rate of A549 cells, the effect is perceived after 48 h, as approved by the quantitative expression of Bcl-xL and Casp 9 genes, and also genotoxicity assays. CONCLUSION: Long-term apoptotic effect of GBA-SLNs compared with GBA may be due to the accumulation of GBA-SLNs in the tumor site because of deviant tumor pathology. Our data confirmed that SLNs could be exploited for sustained lipophilic GBA delivery.

Nano graphene oxide: a novel carrier for oral delivery of flavonoids.

The interesting physical and chemical properties of graphene oxide (GO) have led to much excitement among biomedical scientists in recent years. It is known that many potent, often aromatic medicines are water insoluble, and this has hindered their administration to treat diseases. Nano GO was synthesized and investigated for its biological application as a carrier for quercetin, a focused bioactive flavonoid widely used as a health supplement and a drug candidate. Different techniques were used to fully evaluate the synthesis, cytotoxicity, and quercetin loading capacity of nano GO. AFM and TEM results confirmed the preparation of planar nanoparticles without aggregation which was verified by reported size results (30 nm) obtained with a particle size analyzer. FTIR and DSC results proved the drug-carrier interaction. In vitro cytotoxicity assays showed that nano GO had no cytotoxicity on A549 cells in different amounts after incubation for 72 h, confirming its suitability as a drug carrier. Our results showed that nano GO can be proposed as a new carrier due to its small size, large specific surface area, low cost, and useful non-covalent interactions with aromatic low-soluble flavonoids such as quercetin. Moreover, it may find widespread applications in biomedicine.

Drug targeting using solid lipid nanoparticles.

The present review aims to show the features of solid lipid nanoparticles (SLNs) which are at the forefront of the rapidly developing field of nanotechnology with several potential applications in drug delivery and research. Because of some unique features of SLNs such as their unique size dependent properties it offers possibility to develop new therapeutics. A common denominator of all these SLN-based platforms is to deliver drugs into specific tissues or cells in a pathological setting with minimal adverse effects on bystander cells. SLNs are capable to incorporate drugs into nanocarriers which lead to a new prototype in drug delivery which maybe used for drug targeting. Hence solid lipid nanoparticles hold great promise for reaching the goal of controlled and site specific drug delivery and hence attracted wide attention of researchers. This review presents a broad treatment of targeted solid lipid nanoparticles discussing their types such as antibody SLN, magnetic SLN, pH sensitive SLN and cationic SLN.

Preparation of a new electrochemical sensor based on iron (III) complexes modified carbon paste electrode for simultaneous determination of mefenamic acid and indomethacin.

A new chemically modified carbon paste electrodes based on Fe (III) schiff base (Fe (III)-SBMCP)-containing graphite pastes were prepared and evaluated as electrochemical sensor for the voltammetric determination of mefenamic acid and indomethacin in aqueous solutions. The measurements were carried out by application of the differential pulse voltammetry (DPV) method in phosphate buffer solution with pH 3.5. Fe (III) loaded in schiff base can increase anodic peak currents by adsorption of mefenamic acid and indomethacin on electrode surface. The prepared electrode shows voltammetric responses with high sensitivity for mefenamic acid and indomethacin in optimal conditions, which makes it very suitable for simultaneous determination of these compounds. The proposed method was successfully applied for determination mefenamic acid and indomethacin in commercial tablet samples.

Preparation, characterization, and DNA binding studies of water-soluble quercetin--molybdenum(VI) complex.

DNA binding studies of flavonoids are needed to understand the reaction mechanism and improve drugs that target DNA. Quercetin (Q) is one of the most common flavonoids that can chelate metal ions and interact with double-stranded DNA. In the present work, UV absorption spectrophotometry, viscosimetry, circular dichroism, and fluorescence spectroscopic techniques were employed to study the interaction of water-soluble quercetin--molybdenum(VI) complex [Q-Mo(VI)] with calf thymus DNA. The binding constants (K(b)) for the complex with DNA were estimated to be 2.9 × 10(3) through spectroscopic titrations. Upon addition of the complex, significant decreases were observed in the viscosity of calf thymus DNA. Circular dichroic spectra indicated that there are certain detectable conformational changes in the DNA double helix when complex was added. Further, competitive methylene blue binding studies with fluorescence spectroscopy have shown that the complex can bind to DNA through nonintercalative mode. The experimental results suggest that Q-Mo(VI) binds to DNA via an outside binding mode.

Molecular aspects on the interaction of quercetin and its metal complexes with DNA.

Flavonoids occupy an important position in chemistry and pharmacology. Various flavonoids, particularly quercetin have potential to form molecular complexes with nucleic acid structure and have attracted recent attention for their prospective clinical and pharmacological utility. This review highlights the properties of quercetin and its different metal complexes as well as their interactions with DNA reported by several research groups. Various analytical techniques were employed including absorbance, fluorescence and circular dichroism spectroscopies, viscosity and voltammetry to provide more details about binding mechanism of these materials with DNA.

Spectroscopic studies on the interaction of quercetin-terbium(III) complex with calf thymus DNA.

The interaction of native calf thymus DNA (CT-DNA) with quercetin-terbium(III) [Q-Tb(III)] complex at physiological pH was monitored by UV absorption spectrophotometry, circular dichroism, fluorescence spectroscopy, and viscosimetric techniques. The complex displays binding properties to the CT-DNA and was found to interact with CT-DNA through outside binding, demonstrated by a hypochromic effect of Q-Tb(III) on the UV spectra of CT-DNA and the calculated association constants (K). Also, decrease in the specific viscosity of CT-DNA, decrease in the fluorescence intensity of Q-Tb(III) solutions in the presence of increasing amounts of CT-DNA, and detectable changes in the circular dichroism spectrum of CT-DNA are other evidences to indicate that Q-Tb(III) complex interact with CT-DNA through outside binding.