Nanofabrication of chitosan-based dressing to treat the infected wounds: in vitro and in vivo evaluations.

Aim: Here, an innovative kind of antibacterial nanocomposite film is developed by incorporating graphene oxide and zinc oxide into chitosan matrix. Materials & methods: Our dressing was fabricated using the solution casting method. Fourier transform infrared spectra and TGA-DTG clearly confirmed the structure of film dressing. Results & conclusion: Our results showed the tensile strength and elongation at the break of the films were 20.1 ± 0.7 MPa and 36 ± 10%, respectively. Our fabricated film could absorb at least three-times the fluid of its dry weight while being biocompatible, antibacterial, non-irritant and non-allergic. In addition, it accelerated the healing process of infected wounds by regulating epithelium thickness and the number of inflammatory cells, thus it may be useful for direct application to damaged infected wounds.

In this study, an innovative kind of antibacterial nanocomposite film is developed by incorporating graphene oxide and zinc oxide into chitosan matrix. Our antibacterial wound dressing was fabricated using the solution casting method. Our fabricated film could absorb at least three-times the fluid of its dry weight while being biocompatible, antibacterial, non-irritant and non-allergic. In addition, our film accelerated the healing process of infected wounds by regulating epithelium thickness and the number of inflammatory cells. thus it may be useful for direct application to damaged infected wounds.

Reduced graphene oxide coated alginate scaffolds: potential for cardiac patch application.

BACKGROUND: Cardiovascular diseases, particularly myocardial infarction (MI), are the leading cause of death worldwide and a major contributor to disability. Cardiac tissue engineering is a promising approach for preventing functional damage or improving cardiac function after MI. We aimed to introduce a novel electroactive cardiac patch based on reduced graphene oxide-coated alginate scaffolds due to the promising functional behavior of electroactive biomaterials to regulate cell proliferation, biocompatibility, and signal transition. METHODS: The fabrication of novel electroactive cardiac patches based on alginate (ALG) coated with different concentrations of reduced graphene oxide (rGO) using sodium hydrosulfite is described here. The prepared scaffolds were thoroughly tested for their physicochemical properties and cytocompatibility. ALG-rGO scaffolds were also tested for their antimicrobial and antioxidant properties. Subcutaneous implantation in mice was used to evaluate the scaffolds' ability to induce angiogenesis. RESULTS: The Young modulus of the scaffolds was increased by increasing the rGO concentration from 92 ± 4.51 kPa for ALG to 431 ± 4.89 kPa for ALG-rGO-4 (ALG coated with 0.3% w/v rGO). The scaffolds' tensile strength trended similarly. The electrical conductivity of coated scaffolds was calculated in the semi-conductive range (~ 10-4 S/m). Furthermore, when compared to ALG scaffolds, human umbilical vein endothelial cells (HUVECs) cultured on ALG-rGO scaffolds demonstrated improved cell viability and adhesion. Upregulation of VEGFR2 expression at both the mRNA and protein levels confirmed that rGO coating significantly boosted the angiogenic capability of ALG against HUVECs. OD620 assay and FE-SEM observation demonstrated the antibacterial properties of electroactive scaffolds against Escherichia coli, Staphylococcus aureus, and Streptococcus pyogenes. We also showed that the prepared samples possessed antioxidant activity using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay and UV-vis spectroscopy. Histological evaluations confirmed the enhanced vascularization properties of coated samples after subcutaneous implantation. CONCLUSION: Our findings suggest that ALG-rGO is a promising scaffold for accelerating the repair of damaged heart tissue.

Electrically conductive carbon-based (bio)-nanomaterials for cardiac tissue engineering.

A proper self-regenerating capability is lacking in human cardiac tissue which along with the alarming rate of deaths associated with cardiovascular disorders makes tissue engineering critical. Novel approaches are now being investigated in order to speedily overcome the challenges in this path. Tissue engineering has been revolutionized by the advent of nanomaterials, and later by the application of carbon-based nanomaterials because of their exceptional variable functionality, conductivity, and mechanical properties. Electrically conductive biomaterials used as cell bearers provide the tissue with an appropriate microenvironment for the specific seeded cells as substrates for the sake of protecting cells in biological media against attacking mechanisms. Nevertheless, their advantages and shortcoming in view of cellular behavior, toxicity, and targeted delivery depend on the tissue in which they are implanted or being used as a scaffold. This review seeks to address, summarize, classify, conceptualize, and discuss the use of carbon-based nanoparticles in cardiac tissue engineering emphasizing their conductivity. We considered electrical conductivity as a key affecting the regeneration of cells. Correspondingly, we reviewed conductive polymers used in tissue engineering and specifically in cardiac repair as key biomaterials with high efficiency. We comprehensively classified and discussed the advantages of using conductive biomaterials in cardiac tissue engineering. An overall review of the open literature on electroactive substrates including carbon-based biomaterials over the last decade was provided, tabulated, and thoroughly discussed. The most commonly used conductive substrates comprising graphene, graphene oxide, carbon nanotubes, and carbon nanofibers in cardiac repair were studied.

Reduced graphene oxide: osteogenic potential for bone tissue engineering.

Collagen (Col) type I, as the major component of the bone extracellular matrix has been broadly studied for bone tissue engineering. However,inferior mechanical properties limit its usage for load bearing applications. In this research, freeze dried Col scaffolds are coated with graphene oxide (GO) through a covalent bond of the amine Col with the graphene carboxyl groups. The prepared scaffolds were then reduced using a chemical agent. Scanning electron microscopy exhibited a porous structure for the synthesized scaffolds with an approximate pore size of 100-220 ± 12 µm, which is in the suitable range for bone tissue engineering application. Reducing the GO coating improved the compressive modulus of the Col from 250 to 970 kPa. Apatite formation was also indicated by immersing the scaffolds in simulated body fluid after five days. The cytocompatibility of the scaffolds, using human bone marrow-derived mesenchymal stem cells, was confirmed with MTT analysis. Alkaline phosphatase assay revealed that reducing the Col-GO scaffolds can effectively activate the differentiation of hBM-MSCs into osteoblasts after 14 days, even without the addition of an osteogenic differentiation medium. The results of this study highlight that GO and its reduced form have considerable potential as bone substitutes for orthopaedic and dental applications.

Antibody-Drug Conjugates: Possibilities and Challenges.

The design of Antibody Drug Conjugates (ADCs) as efficient targeting agents for tumor cell is still in its infancy for clinical applications. This approach incorporates the antibody specificity and cell killing activity of chemically conjugated cytotoxic agents. Antibody in ADC structure acts as a targeting agent and a nanoscale carrier to deliver a therapeutic dose of cytotoxic cargo into desired tumor cells. Early ADCs encountered major obstacles including, low blood residency time, low penetration capacity to tumor microenvironment, low payload potency, immunogenicity, unusual off-target toxicity, drug resistance, and the lack of stable linkage in blood circulation. Although extensive studies have been conducted to overcome these issues, the ADCs based therapies are still far from having high-efficient clinical outcomes. This review outlines the key characteristics of ADCs including tumor marker, antibody, cytotoxic payload, and linkage strategy with a focus on technical improvement and some future trends in the pipeline.

Electroactive graphene oxide-incorporated collagen assisting vascularization for cardiac tissue engineering.

The application of a cardiac patch over the epicardial surface has shown positive effects in protecting cardiac function postinfarction. Electroactive patches could enhance electrical signal propagation among cardiac cells. In the present study, an electrically active composite of collagen and graphene oxide (Col-GO) was fabricated as a cardiac patch. Col scaffolds were fabricated using a freeze-drying method and coated covalently with GO. Some scaffolds were also reduced by a reduction agent to restore the high conductivity of GO. GO was shown to be a single layer with suitable lateral size for biological application. The Col-GO scaffolds contained randomly oriented interconnected pores with appropriate pore sizes of 120-138 ± 8 µm. GO flakes were also well distributed in the pore walls. By increasing the GO concentration, the tensile strength of the scaffolds was enhanced from 75 kPa for Col-GO-5 to 162 kPa for Col-GO-90. Young modulus also followed the same trend. Electrical conductivity of the scaffolds was in the range of semi-conductive materials (~10-4 S/m), which is suitable for cardiac tissue engineering applications. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated no toxic effects on human umbilical vein endothelial cells (HUVECs) after 96 h. Also, a 10-days degradation product of the samples was compatible with HUVECs. Reduced scaffolds supported neonatal cardiomyocyte adhesion and upregulated the expression of the cardiac genes, including Cx43, Actin4, and Trpt-2 than their nonconductive counterparts. The obtained results confirmed the angiogenic properties of reduced Go-containing materials for cardiovascular applications where angiogenesis plays an important role, especially postinfarction. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 204-219, 2019.

Placenta-specific1 (PLAC1) is a potential target for antibody-drug conjugate-based prostate cancer immunotherapy.

Our recent findings strongly support the idea of PLAC1 being as a potential immunotherapeutic target in prostate cancer (PCa). Here, we have generated and evaluated an anti-placenta-specific1 (PLAC1)-based antibody drug conjugate (ADC) for targeted immunotherapy of PCa. Prostate cancer cells express considerable levels of PLAC1. The Anti-PLAC1 clone, 2H12C12, showed high reactivity with recombinant PLAC1 and selectivity recognized PLAC1 in prostate cancer cells but not in LS180 cells, the negative control. PLAC1 binding induced rapid internalization of the antibody within a few minutes which reached to about 50% after 15 min and almost completed within an hour. After SN38 conjugation to antibody, a drug-antibody ratio (DAR) of about 5.5 was achieved without apparent negative effect on antibody affinity to cell surface antigen. The ADC retained intrinsic antibody activity and showed enhanced and selective cytotoxicity with an IC50 of 62 nM which was about 15-fold lower compared to free drug. Anti-PLAC1-ADC induced apoptosis in human primary prostate cancer cells and prostate cell lines. No apparent cytotoxic effect was observed in in vivo animal safety experiments. Our newly developed anti-PLAC1-based ADCs might pave the way for a reliable, efficient, and novel immunotherapeutic modality for patients with PCa.

Facile fabrication of nickel immobilized on magnetic nanoparticles as an efficient affinity adsorbent for purification of his-tagged protein.

In the present research, an efficient, convenient, and inexpensive method for the one-pot synthesis of Fe3O4@Histidine is developed. Histidine is readily loaded on magnetic nanoparticles by one step and simple method without any supplemental linkers. In the structure of Fe3O4@Histidine, histidine covalently immobilized on the surface of Fe3O4, magnetic nanoparticles are able to trap Ni2+ ions through a strong interaction between nickel and histidines in protein tag. Two coordination sites of nickel are occupied with ligand on the surface of magnetic nanoparticles and four coordination sites have been remained that these sites will be occupied with histidine tag of recombinant protein A. The functionalized nanoparticles were spherical and well separated with an average diameter around 30nm. The obtained magnetic nanoparticles have a saturation magnetization of about 54emu/g. Fe3O4@Histidine-Ni was used to enrich and purify 6×histidine-tagged recombinant protein-A directly from the mixture of lysed cells. It has been found that Ni(II)-immobilized Fe3O4@Histidine magnetic nanoparticles present negligible nonspecific protein adsorption and high His-tag protein binding capacity The average binding capacity (MW 42k Da), is 700±25µg·mg-1 (protein/Fe3O4@Histidine-Ni).

Nickel-Salen supported paramagnetic nanoparticles for 6-His-target recombinant protein affinity purification.

In this research, a simple, efficient, inexpensive, rapid and high yield method for the purification of 6×histidine-tagged recombinant protein was developed. For this purpose, manganese ferrite magnetic nanoparticles (MNPs) were synthesized through a co-precipitation method and then they were conveniently surface-modified with tetraethyl orthosilicate (TEOS) in order to prevent oxidation and form high density of hydroxyl groups. Next, the salen ligand was prepared from condensation reaction of salicylaldehyde and 3-aminopropyl (trimethoxy) silane (APTMS) in 1:1 molar ratio; followed by complexation with Ni(OAc)2.4H2O. Finally, the prepared Ni(II)-salen complex conjugated to silica coated MNPs and MnFe2O4@SiO2@Ni-Salen complex nanoparticles were obtained. The functionalized nanoparticles were spherical with an average diameter around 70nm. The obtained MNPs had a saturation magnetization about 54 emu/g and had super paramagnetic character. These MNPs were used efficiently to enrich recombinant histidine-tagged (His-tagged) protein-A from bacterial cell lysate. In about 45min, highly pure His-tagged recombinant protein was obtained, as judged by SDS-PAGE analysis and silver staining. The amount of target protein in flow through and washing fractions was minimal denoting the high efficiency of purification process. The average capacity of the matrix was found to be high and about 180±15mgg-1 (protein/MnFe2O4@SiO2@Ni-Salen complex). Collectively, purification process with MnFe2O4@SiO2@Ni-Salen complex nanoparticles is rapid, efficient, selective and whole purification can be carried out in only a single tube without the need for expensive systems.

Improving the luminescence properties of aequorin by conjugating to CdSe/ZnS quantum dot nanoparticles: Red shift and slowing decay rate.

Changing the properties of photoprotein aequorin such as the wavelength emission and decay half-life by using bioluminescence resonance energy transfer (BRET) phenomenon is the main aim in this paper. BRET system was set up with CdSe/ZnS quantum dot nanoparticles as an acceptor molecule and photoprotein as an energy donor molecule. Quantum dots are semiconductor nanoparticles with very interesting optical properties, including broad excitation spectra, narrow and the symmetric band width emission spectra, tunable by their sizes, compositions, negligible photo-bleaching and good chemical and photo-stability. In this QD-BRET system, aequorin is conjugated to the carboxyl groups on quantum dot surface by EDC/NHS chemistry as cross linker. Bioluminescence energy generates by aequorin upon adding Ca(2+) and transfers to the quantum dots in a radiationless manner and emits at a longer wavelength. The determined bioluminescent parameters for this method included aequorin activity, emission spectra and decay half-life time. In fact, this spectrum tuning strategy resulted in a change in bioluminescent properties of photoprotein, therefore, the maximum emission wavelength shifted from 455 to 540nm and the decay time increased from 3.76 to 12.11s. Nowadays, photoproteins with different characteristics are capable of being employed as a reporter in multi-analyte detections and in vivo imaging.

Inorganic-organic hybrid silica based tin complex as a novel, highly efficient and recyclable heterogeneous catalyst for the one-pot preparation of spirooxindoles in water.

In the present study, a tin complex immobilized on silica gel as a novel, green, highly efficient and heterogeneous reusable catalyst was synthesized by grafting 2-amino benzamide onto the silica gel surface as a result of the reaction between isatoic anhydride and 3-aminopropyl-functionalized silica gel, followed by complexing with tin chloride. The resulting organic-inorganic hybrid material was evaluated in the one-pot three-component synthesis of spiro[indoline-pyrazolo[4',3':5,6]pyrido[2,3-d]pyrimidine]trione derivatives in water via the condensation reaction of isatins, barbituric acids, and 1H-pyrazol-5-amines. All the reactions were completed in short reaction times and all the products were obtained in high to excellent yields with high purity. In addition, the synthesized novel catalyst could be separated from the reaction mixture by simple filtration and can be reused up to seven runs without significant loss in activity.

A facile one-pot ultrasound assisted for an efficient synthesis of 1H-spiro[furo[3,4-b]pyridine-4,3'-indoline]-3-carbonitriles.

A convenient one-pot protocol was developed for the synthesis of 1H-spiro[furo[3,4-b]pyridine-4,3'-indoline]-3-carbonitrile derivatives. This reaction was carried out through a three component condensation reaction of isatins, malononitrile, and anilinolactones in the presence of a catalytic amount of Et3N as an inexpensive and available basic catalyst in THF under ultrasound irradiation. The products were obtained in high yields and short reaction times. The main advantage of this synthetic method is that the obtained products in ultrasonic irradiations are different from classical heating.

Copper ferrite nanoparticles: an efficient and reusable nanocatalyst for a green one-pot, three-component synthesis of spirooxindoles in water.

A green reaction of isatins, active cyanomethanes, and cyclic 1,3-dicarbonyl derivatives for the efficient and simple one-pot three-component synthesis of spirooxindole fused heterocycles in refluxing water by use of magnetically recoverable and reusable catalyst is reported. The features of this procedure are, the use of magnetically recoverable and reusable catalyst, mild reaction conditions, high to excellent product yields, operational simplicity, and easy workup procedures. Most importantly of all, easy magnetic separation of the catalyst eliminates the requirement of catalyst filtration after completion of the reaction. Furthermore, the catalyst remained highly active even after 5 repeated uses.

Ultrasound-assisted synthesis of 2,2'-(2-oxoindoline-3,3-diyl)bis(1H-indene-1,3(2H)-dione) derivatives.

A simple and efficient procedure for the synthesis of 2,2'-(2-oxoindoline-3,3-diyl)bis(1H-indene-1,3(2H)-dione) derivatives, 2,2'-(2-oxo-1,2-dihydroacenaphthylene-1,1-diyl)bis(1H-indene-1,3(2H)-dione) and 2,2'-(1,3-dioxo-2,3-dihydro-1H-indene-2,2-diyl)bis(1H-indene-1,3(2H)-dione) by the reaction of 1,3-indandione and isatins or acenaphthylene-1,2-dione or ninhydrine in ethanol under ultrasonic irradiation in the presence of p-TSA is reported. The advantages of this method are the use of an inexpensive and readily available catalyst, easy work-up, good yields, and the use of ethanol as a solvent that is considered to be relatively environmentally benign.

Three-component synthesis of 2-oxoindolin-3-ylphosphonates.

A one-pot, three-component and catalyst-free method for the efficient and simple synthesis of dialkyl 3-(dicyanomethyl)-2-oxoindolin-3-ylphosphonates at 50 degrees C under solvent-free conditions is reported. The features of this procedure are mild reaction conditions, high yields of products, and operational simplicity.

Chromeno[2,3-d]pyrimidine-triones synthesis by a three-component coupling reaction.

A simple and one-pot synthesis of new chromeno[2,3-d]pyrimidine-triones by a three-component condensation reaction of barbituric acids, aldehydes and cyclohexane-1,3-diones in refluxing ethanol in the presence of p-toluenesulfonic acid (p-TSA) for 3-10 h is reported. Two cyclohexane-1,3-diones, four barbituric acids and six substituted aldehydes were chosen for the library validation. Prominent among the advantages of this new method are operational simplicity, good yields and easy work-up procedures employed.

Simple and catalyst-free synthesis of oxoindolin-3-yl phosphonates.

An efficient, simple, and catalyst-free synthesis of dialkyl or diaryl 3-(dicyanomethyl)-2-oxoindolin-3-ylphosphonates by the reaction of dialkyl or diaryl phosphites and oxoindolin-3-ylidenemalononitriles under solvent-free conditions is reported. The reaction of imino isatins with dialkyl or diaryl phosphites results in the formation of dialkyl or diaryl 2-oxo-3-(arylamino)indolin-3-ylphosphonates.

WITHDRAWN: Sonochemical three-component synthesis of pyrazolotriazoles.

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One-pot, pseudo four-component synthesis of a spiro[diindeno[1,2-b:2',1'-e]pyridine-11,3'-indoline]-trione library.

A one-pot, pseudo four-component method for the efficient and simple synthesis of spiro[diindeno[1,2-b:2',1'-e]pyridine-11,3'-indoline]-2',10,12-trione derivatives in refluxing acetonitrile is reported. The features of this procedure are mild reaction conditions, high yields of products, and operational simplicity.

Ultrasound-assisted one-pot, three-component synthesis of spiro[indoline-3,4'-pyrazolo[3,4-b]pyridine]-2,6'(1'H)-diones in water.

A simple, facile, efficient and three-component procedure for the synthesis of spiro[indoline-3,4'-pyrazolo[3,4-b]pyridine]-2,6'(1'H)-diones by the reaction of 4-hydroxycumarin, isatins and 1H-pyrazol-5-amines in water under ultrasonic irradiation is reported. The advantages of this method are the use of an inexpensive and readily available catalyst, easy work-up, good yields, and the use of water as a solvent that is considered to be relatively environmentally benign.