Biolmpacts
Volume:9 Issue: 1, Mar 2019

Trafficking of macromolecular immunotherapy agent into the tumor microenvironment (TME) is a challenging issue. In the TME, cancer cells exploit indoleamine 2, 3-dioxygenase (IDO), as a cytosolic enzyme that catalyzes the L-tryptophan (Trp) through the kynurenine (Kyn) pathway, which could negatively regulate the activity of T cells. Thus, Trp/Kyn pathway, can be targeted with novel treatment modalities such as IDO1 inhibitor to benefit patients with aggressive solid tumors.

In recent years, more attention was dedicated to developing new methods for designing of drug delivery systems. The aim of present work is to improve the efficiency of the antibacterial drug delivery process, and to realize and to control accurately the release. First, graphene oxide (GO) was prepared according to the modified Hummers method then the GO was modified with carboxymethylcellulose (CMC) and Zn-based metal-organic framework (MOF-5) through the solvothermal technique. Performing the various analysis methods including scanning electron microscope (SEM), X-ray diffraction (XRD), EDX, Fourier transform infrared (FTIR) spectroscopy and Zeta potentials on the obtained bio-nanocomposite showed that the new modified GO has been prepared. With using common analysis methods the structure of synthesized materials was determined and confirmed and finally, their antibacterial behavior was examined based on the broth microdilution methods. Carboxymethylcellulose/MOF-5/GO bio-nanocomposite (CMC/MOF-5/GO) was successfully synthesized through the solvothermal technique. Tetracycline (TC) was encapsulated in the GO and CMC/MOF-5/GO. The drug release tests showed that the TC-loaded CMC/MOF5/GO has an effective protection against stomach pH. With controlling the TC release in the gastrointestinal tract conditions, the long-time stability of drug dosing was enhanced. Furthermore, antibacterial activity tests showed that the TC-loaded CMC/MOF-5/GO has an antibacterial activity to negatively charge E. coli bacteria in contrast to TC-loaded GO.

The bacterial enzyme has gained more attention in therapeutic application because of the higher substrate specificity and longer half-life. L-asparaginase is an important enzyme with known antineoplastic effect against acute lymphoblastic leukemia (ALL). Novel L-asparaginase genes were identified from a locally isolated halo-thermotolerant Bacillus strain and the recombinant enzymes were overexpressed in modified E. coli strains, OrigamiTM B and BL21. In addition, the biochemical properties of the purified enzymes were characterized, and the enzyme activity was evaluated at different temperatures, pH, and substrate concentrations. The concentration of pure soluble enzyme obtained from Origami strain was ~30 mg/L of bacterial culture, which indicates the significant improvement compared to L-asparaginase produced by E. coli BL21 strain. The catalytic activity assay on the identified L-asparaginases (ansA1 and ansA3 genes) from Bacillus sp. SL-1 demonstrated that only ansA1 gene codes an active and stable homologue (ASPase A1) with high substrate affinity toward L-asparagine. The Kcat and Km values for the purified ASPase A1 enzyme were 23.96s-1 and 10.66 µM, respectively. In addition, the recombinant ASPase A1 enzyme from Bacillus sp. SL-1 possessed higher specificity to L-asparagine than L-glutamine. The ASPase A1 enzyme was highly thermostable and resistant to the wide range of pH 4.5–10. The biochemical properties of the novel ASPase A1 derived from Bacillus sp. SL-l indicated a great potential for the identified enzyme in pharmaceutical and industrial applications.

The major complications of stent implantation are restenosis and late stent thrombosis. PBMA polymers are used for stent coating because of their mechanical properties. We previously synthesized and characterized Dextrangraft-polybutylmethacrylate copolymer (Dex-PBMA) as a potential stent coating. In this study, we evaluated the haemocompatibility and biocompatibility properties of Dex-PBMA in vitro and in vivo. Here, we investigated: (1) the effectiveness of polymer coating under physiological conditions and its ability to release Tacrolimus®, (2) the capacity of Dex-PBMA to inhibit Staphylococcus aureus adhesion, (3) the thrombin generation and the human platelet adhesion in static and dynamic conditions, (4) the biocompatibility properties in vitro on human endothelial colony forming cells ( ECFC) and on mesenchymal stem cells (MSC) and in vivo in rat models, and (5) we implanted Dex-PBMA and Dex-PBMATAC coated stents in neointimal hyperplasia restenosis rabbit model. Dex-PBMA coating efficiently prevented bacterial adhesion and release Tacrolimus®. Dex-PBMA exhibit haemocompatibility properties under flow and ECFC and MSC compatibility. In vivo, no pathological foreign body reaction was observed neither after intramuscular nor intravascular aortic implantation. After Dex-PBMA and Dex-PBMATAC coated stents 30 days implantation in a restenosis rabbit model, an endothelial cell coverage was observed and the lumen patency was preserved. Based on our findings, Dex-PBMA exhibited vascular compatibility and can potentially be used as a coating for metallic coronary stents.

Skin can be used as a site for local and systemic drug administration. Diffusion of drugs through the skin has led to the development of different transdermal drug delivery systems. Curcumin is a wound healing and anti-inflammatory agent. Curcumin was incorporated into biocomposite films of carrageenan (κC)/locust bean gum (LBG)/ montmorillonite (MMT) prepared by a solvent casting method. Film-forming solutions were prepared by adding and 2.5% v/v of propylene glycol and MMT (30% w/w). The curcumin loaded polymer composite transdermal films were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) spectroscopy and X-ray diffraction (XRD) analysis. Mechanical properties in terms of tensile strength and extensibility were studied. Films were also evaluated for moisture content, moisture uptake, thickness, folding endurance, swelling ratio and water vapor transmission rate (WVTR). κC and κC/L40 showed the highest percent cumulative release of 80.42±1.61% and 69.38±1.26% among all of the polymer composite transdermal films in 8 hours and 24 hours respectively. In vitro release profiles showed that increasing concentration of LBG and MMT sustained the release of the drug from the polymer composite transdermal films. Decreased percent cumulative release as the concentration of LBG and MMT increases in polymer composite transdermal film.

Triple-negative breast cancer (TNBC) is an important subtype of breast cancer, which occurs in the absence of estrogen, progesterone and HER-2 receptors. According to the recent studies, TNBC may be a cancer testis antigen (CTA)-positive tumor, indicating that the CTA-based cancer vaccine can be a treatment option for the patients bearing such tumors. Of these antigens (Ags), the MAGE-A family and NY-ESO-1 as the most immunogenic CTAs are the potentially relevant targets for the development of an immunotherapeutic way of the breast cancer treatment. In the present study, immunoinformatics approach was used to design a multi-epitope peptide vaccine to combat the TNBC. The vaccine peptide was constructed by the fusion of three crucial components, including the CD8+ cytotoxic T lymphocytes (CTLs) epitopes, helper epitopes and adjuvant. The epitopes were predicted from the MAGE-A and NY-ESO-1 Ags. In addition, the granulocyte-macrophage-colony-stimulating factor (GM-CSF) was used as an adjuvant to promote the CD4+ T cells towards the T-helper for more strong induction of CTL responses. The components were conjugated by proper linkers. The vaccine peptide was examined for different physiochemical characteristics to confirm the safety and immunogenic behavior. Furthermore, the 3D-structure of the vaccine peptide was predicted based on the homology modeling approach using the MODELLER v9.17 program. The vaccine structure was also subjected to the molecular dynamics simulation study for structure refinement. The results verified the immunogenicity and safety profile of the constructed vaccine as well as its capability for stimulating both the cellular and humoral immune responses. Based on our in-silico analyses, the proposed vaccine may be considered for the immunotherapy of TNBC.

The aim of this research was to study the impact of various doxorubicin (Dox)-containing nanofluids, e.g. singlewalled carbon nanotube (SWCNT)+Dox, graphene oxide (GO)+Dox and DextranPNIPAM (copolymer)+Dox mixtures on HeLa cells (human transformed cervix epithelial cells, as a model for cancer cells) depending on their concentration. Structural analysis of GO+Dox complex was accomplished using Hartree-Fock level of theory in 6-31G** basis set in Gaussian. Dynamic light scattering (DLS), zeta-potential, scanning electron microscopy and confocal laser scanning microscopy were used. The cell viability was analyzed by the MTT assay. The viability of HeLa cells was studied with the MTT assay after the incubation with various Dox-containing dispersions depending on their concentration. The size of the particles was determined by DLS. The morphology of the nanoparticles (NPs) was studied by scanning electron microscopy and their uptake into cells was visualized by confocal laser scanning microscopy. It was found that the Dextran-PNIPAM+Dox nanofluid in contrast to Dox alone showed higher toxicity towards HeLa cells up to 80% after 24 hours of incubation, whereas the SWCNT+Dox and GO+Dox nanofluids at the same concentrations protected cells from Dox. The importance of Dextran-PNIPAM copolymer as a universal platform for drug delivery was established, and the huge potential of Dextran-PNIPAM+Dox NPs as novel anticancer agents was noted. Based on the in vitro study of the SWCNT+Dox and GO+Dox nanofluids, it was concluded that SWCNT and GO NPs can be effective cytoprotectors against the highly toxic drugs.

This corrects the article "A cancer vaccine with dendritic cells differentiated with GM-CSF and IFNα and pulsed with a squaric acid treated cell lysate improves T cell priming and tumor growth control in a mouse model" published on 2018: Volume 08, Issue 03, Pages 211-221. Correction to: BioImpacts 10.15171/bi.2018.24, published on 2018: Volume 08, Issue 03 The original version of this article contained a typographical error in the spelling of the author Lana E. Kandalaft, which was incorrectly given as Lana Kandalaft. This has now been corrected in the PDF and HTML versions of the article.