IgG antibodies mediated gold nanoparticles conjugated to methotrexate as targeted chemotherapy for lung cancer.

Vincamine, a natural chemical, was used as a reducing agent in the synthesis of IgG antibodies mediated biogenic gold nanoparticles (IgGAuNPs). Eventually, the synthesised IgGAuNPs were bioconjugated with the chemotherapeutic drug methotrexate (MTX-IgGAuNPs). The IgG isotype can target cancer cells through polymorphic Fc gamma receptors (FcγRs) and have therapeutic effects. They can restrict cell division by inhibiting different intracellular signal transduction pathways and activating NK cells and macrophages through antibody-dependent cellular cytotoxicity and macrophage-mediated antibody-dependent phagocytosis, respectively. Further, IgGAuNPs and MTX-IgGAuNPs were characterised by physical techniques. Moreover, 3D conformational changes in the structure of IgG were analysed by fluorescence spectroscopy during and after the synthesis of IgGAuNPs. Furthermore, the IgGAuNPs and MTX-IgGAuNPs were effective against lung cancer (A549 cells), while they were found to be non-toxic against normal cells (NRK cells). The effectiveness of IgGAuNPs and MTX-IgGAuNPs was examined by MTT cytotoxicity assay, DCFDA method for the production of ROS, and release of Cyt-c from the mitochondria for caspase-3-mediated apoptosis. Moreover, the confirmation of internalisation of particles into the nucleus was examined under the DAPI assay, and it was found that particles caused nuclear fragmentation, which was also an indication of apoptosis.

Differential gene expression analysis of RAGE-S100A6 complex for target selection and the design of novel inhibitors for anticancer drug discovery.

Receptor for advanced glycation end products (RAGE), a member of the immunoglobulin family, interactions with its ligands trigger downstream signaling and induce an inflammatory response linked to diabetes, inflammation, carcinogenesis, cardiovascular disease, and a variety of other human disorders. The interaction of RAGE and S100A6 has been associated with a variety of malignancies. For the control of RAGE-related illnesses, there is a great demand for more specialized drug options. To identify the most effective target for combating human malignancies associated with RAGE-S100A6 complex, we conducted single and differential gene expression analyses of S100A6 and RAGE, comparing normal and malignant tissues. Further, a structure-based virtual screening was conducted using the ZINC15 database. The chosen compounds were then subjected to a molecular docking investigation on the RAGE active site region, recognized by the various cancer-related RAGE ligands. An optimized RAGE structure was screened against a library of drug-like molecules. The screening results suggested that three promising compounds were presented as the top acceptable drug-like molecules with a high binding affinity at the RAGE V-domain catalytic region. We depicted that these compounds may be potential RAGE inhibitors and could be used to produce a successful medication against human cancer and other RAGE-related diseases based on their various assorted parameters, binding energy, hydrogen bonding, ADMET characteristics, etc. MD simulation on a time scale of 50 ns was used to test the stability of the RAGE-inhibitor complexes. Therefore, targeting RAGE and its ligands using these drug-like molecules may be an effective therapeutic approach.

Targeted non AR mediated smart delivery of abiraterone to the prostate cancer.

Prostate cancer is the second-deadliest tumor in men all over the world. Different types of drugs with various delivery systems and pathways were developed, but no one showed prominent results against cancer. Meanwhile, nanoparticles have shown good results against cancer. Therefore, in the given study, citrate mediated synthesized gold nanoparticles (CtGNPs) with immobilized survivin antibodies (SvGNPs) were bioconjugated to the substantially potent drug abiraterone (AbSvGNPs) to develop as a combinatorial therapeutic against prostate cancer. The AbSvGNPs are made up of CtGNPs, survivin antibodies, and abiraterone. The selected drug abiraterone (Abira) possesses exceptionally good activity against prostate cancer, but cancer cells develop resistance against this drug and it also poses several severe side effects. Meanwhile, survivin antibodies were used to deliver AbSvGNPs specifically into cancer cells by considering survivin, an anti-apoptotic overexpressed protein in cancer cells, as a marker. The survivin antibodies have also been used to inhibit cancer cells as an immunotherapeutic agent. Similarly, CtGNPs were discovered to inhibit cancer cell proliferation via several transduction pathways. The given bioconjugated nanoparticles (AbSvGNPs) were found to be substantially effective against prostate cancer with an IC50 of 11.8 and 7.3 µM against DU145 and PC-3 cells, respectively. However, it was found safe against NRK and showed less than 25% cytotoxicity up to 20µM concentration. The as-synthesized nanoparticles CtGNPs, SvGNPs, and AbSvGNPs were characterized by several physical techniques to confirm their synthesis, whereas the immobilization of survivin antibodies and bioconjugation of Abira was confirmed by UV-visible spectroscopy, DLS, TEM, FTIR, and zeta-potential. The anticancer potential of AbSvGNPs was determined by MTT, DAPI, ROS, MITO, TUNEL ASSAY, and caspase-3 activity against DU145 and PC3 cells.

Novel Bioengineered Antibacterial and Anticancer ZnO Nanoparticles.

Transition metal oxide NPs have delivered wide applications in various fields. Therefore, in this study, a novel fungus, Alternaria sp. (NCBI Accession No: MT982648) was isolated and characterized from the vicinity of medicinal plants. Eventually, in this method extracted proteins from isolated fungus were utilized to synthesize highly biocompatible zinc nanoparticles (ZnO NPs). The various physical techniques including UV-visible spectroscopy, TEM, HR-TEM, XRD, DLS, zeta potential, and FTIR were used to characterize particles. The UV-visible absorption (λMax) and binding energy for the as-synthesized particles were found to be 329 nm and 3.91 eV, respectively. Further, the polydispersed particles were revealed to have regular crystallinity with hexagonal wurtzite phase of ZnO with the spacing of ~2.46 Å under XRD and HR-TEM. The average size of a particle under TEM was found to be ~18 nm. The evaluation of various surface functional groups of particles was done by FTIR. The average hydrodynamic diameter of particles was found to be ~57 d. nm with 0.44 particle distribution index whereas the nanoemulsion stability was explained by Zeta potential (-9.47 mV). These particles were found to exhibit potential antibacterial and anticancer activities. They were found to be bactericidal against S. abony (MIC 5.73 µg/mL); B. pumilis (MIC 6.64 µg/mL); K. pneumonia (MIC 14.4 µg/mL); E. coli (MIC 8.7 µg/mL); B. subtilis (MIC 5.63 µg/mL) and S. aureus (MIC 12.04 µg/mL). Further, they are also found to be concentration-dependent anticancer and inhibited the growth of A549 cells (IC50-65.3 µg/mL) whereas they were found to demonstrate no any cytotoxicity against NRK normal kidney cell line. The internalization of particles into the nucleus (i.e., nuclear fragmentation and DNA damage) was confirmed by DAPI staining. The intracellular particles were found to generate excessive ROS. Further, the anticancer potential was also estimated by noticing a hike in oxidative stress parameters, cell viability, cell morphology, and change in mitochondrial membrane potential. We effectively synthesized potentially potent antibacterial and anticancer novel bioengineered ZnO NPs.

RAGE Inhibitors for Targeted Therapy of Cancer: A Comprehensive Review.

The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin family that is overexpressed in several cancers. RAGE is highly expressed in the lung, and its expression increases proportionally at the site of inflammation. This receptor can bind a variety of ligands, including advanced glycation end products, high mobility group box 1, S100 proteins, adhesion molecules, complement components, advanced lipoxidation end products, lipopolysaccharides, and other molecules that mediate cellular responses related to acute and chronic inflammation. RAGE serves as an important node for the initiation and stimulation of cell stress and growth signaling mechanisms that promote carcinogenesis, tumor propagation, and metastatic potential. In this review, we discuss different aspects of RAGE and its prominent ligands implicated in cancer pathogenesis and describe current findings that provide insights into the significant role played by RAGE in cancer. Cancer development can be hindered by inhibiting the interaction of RAGE with its ligands, and this could provide an effective strategy for cancer treatment.

Potentially Bioactive Fungus Mediated Silver Nanoparticles.

Fungal metabolites, proteins, and enzymes have been rich sources of therapeutics so far. Therefore, in this study, the hypha extract of a newly identified noble fungus (Alternaria sp. with NCBI Accession number: MT982648) was used to synthesize silver nanoparticles (F-AgNPs) to utilize against bacteria, fungi, and lung cancer. F-AgNPs were characterized by using physical techniques, including UV-visible spectroscopy, zeta potential, DLS, XRD, TEM, and HR-TEM. The particles were found to be polydispersed and quasi-spherical in shape under TEM. They had an average size of ~15 nm. The well dispersed particles were found to have consistent crystallinity with cubic phase geometry under XRD and HR-TEM. The presence of different functional groups on the surfaces of biosynthesized F-AgNPs was confirmed by FTIR. The particle distribution index was found to be 0.447 with a hydrodynamic diameter of ~47 d.nm, and the high value of zeta potential (-20.3 mV) revealed the stability of the nanoemulsion. These particles were found to be active against Staphylococcus aureus (multidrug resistance-MDR), Klebsiella pneumonia, Salmonella abony, and Escherichia coli (MDR) with MIC50 10.3, 12.5, 22.69, and 16.25 µg/mL, respectively. Particles also showed inhibition against fungal strains, including A. flavus, A. niger, T. viridens, and F. oxysporium. Their inhibition of biofilm formation by the same panel of bacteria was also found to be very promising and ranged from 16.66 to 64.81%. F-AgNPs also showed anticancer potential (IC50-21.6 µg/mL) with respect to methotrexate (IC50-17.7 µg/mL) against lung cancer cell line A549, and they did not result in any significant inhibition of the normal cell line BEAS-2. The particles were found to alter the mitochondrial membrane potential, thereby disturbing ATP synthesis and leading to high ROS formation, which are responsible for cell membrane damage and release of LDH, intracellular proteins, lipids, and DNA. A high level of ROS also elicits pro-inflammatory signaling cascades that lead to programmed cell death by either apoptosis or necrosis.

Vincamine, a safe natural alkaloid, represents a novel anticancer agent.

Vincamine, a well-known plant alkaloid, has been used as a dietary supplement and as a peripheral vasodilator to combat aging in humans. In this study, for the very first time, we demonstrated that vincamine can function as an anticancer agent in a human alveolar basal epithelial cell line A549 (IC50 = 309.7 µM). The anticancer potential of vincamine in A549 cells was assessed by molecular assays to determine cell viability, generation of intracellular ROS, nuclear condensation, caspase-3 activity and inhibition, and change in mitochondrial membrane potential (ΔΨm). In silico studies predicted that the anti-proliferative potential of vincamine is enhanced by its interaction with the apoptotic protein caspase-3, and that this interaction is driven by two hydrogen bonds and has a high free energy of binding (-5.64 kcal/mol) with an estimated association constant (Ka) of 73.67 µM. We found that vincamine stimulated caspase-3-dependent apoptosis and lowered mitochondrial membrane potential, which ultimately led to cytochrome C release. Vincamine was also found to quench hydroxyl free radicals and deplete iron ions in cancer cells. As a dietary supplement, vincamine is almost non-toxic in BEAS-2B and 3T3-L1 cells. Therefore, we propose that vincamine represents a safe anticancer agent in lung cancer cells. Its role in other cancers has yet to be explored.

Silk Cocoon-Derived Protein Bioinspired Gold Nanoparticles as a Formidable Anticancer Agent.

We synthesized bioinspired sericin encapsulated gold nanoparticles (SGNPs) using HAuCl4 as the starting material in a bottom-up approach. Further, two-dimensional (2D) and three-dimensional (3D) conformational changes (folding and unfolding) in sericin were studied using circular dichroism (CD) and fluorescence spectroscopy, respectively, during and after the synthesis of particles. Finally, the synthesized SGNPs were characterized using several physical techniques to ensure their correct synthesis and study the size, stability, and charge over the surface of particles. At the beginning of the reaction, when gold was in the ionic form (Au+³), sericin exhibited maximum electrostatic interaction and underwent unfolding. Au+³ reduced to Au during the reaction, and sericin regained its 3D confirmation due to a decrease in its native electrostatic interactions. However, CD revealed the same patterns of unfolding and folding; a decrease in α helix and an increase inß3 pleated sheets were noticed. Although the 3D structure of sericin was restored after the synthesis of SGNPs, it was substantially altered. In addition, certain changes in the 2D structure were observed; however, these did not alter the activity of sericin. Furthermore, Fourier-transform infrared spectroscopy (FTIR) confirmed these findings. The SGNPs were found to be effective against lung cancer (A549 cells), with an IC50 of 145.49 ßM, without exerting any toxic effects on normal cells (NRK cells). The effectiveness of SGNPs was examined by MTT cytotoxicity and nuclear fragmentation assays. Furthermore, we assessed their ability to produce excessive ROS and release Cyt-c from the mitochondria for caspase-3-mediated apoptosis.

Protein aggregation as a consequence of non-enzymatic glycation: Therapeutic intervention using aspartic acid and arginine.

Non-enzymatic glycation tempted AGEs of proteins are currently at the heart of a number of pathological conditions. Production of chemically stable AGEs can permanently alter the protein structure and function, concomitantly leading to dilapidated situations. Keeping in perspective, present study aims to report the glycation induced structural and functional modification of a cystatin type isolated from rai mustard seeds, using RSC-glucose and RSC-ribose as model system. Among the sugars studied, ribose was found to be most potent glycating agent as evident from different biophysical assays. During the course of incubation, RSC was observed to pass through a series of structural intermediates as revealed by circular dichroism, altered intrinsic fluorescence and high ANS binding. RSC incubation with ribose post day 36 revealed the possible buildup of ß structures as observed in CD spectral analysis, hinting towards the generation of aggregated structures in RSC. High thioflavin T fluorescence and increased Congo red absorbance together with enhanced turbidity of the modified form confirmed the aggregation of RSC. The study further revealed anti-glycation and anti-aggregation potential of amino acids; aspartic acid and arginine as they prevented and/or slowed down the process of AGEs and ß structure buildup in a concentration dependent manner with arginine proving to be the most effective one.

Sericin-functionalized GNPs potentiate the synergistic effect of levofloxacin and balofloxacin against MDR bacteria.

A gradual expansion in resistant bacterial strains against commercially available antibacterial agents is the serious concern of the given research. It poses critical problem for public health. Thus, the demand for new antimicrobial agents has increased the interest in newer technologies and innovative approaches are required to advance the diagnosis and elimination of causative organisms. In this study, the potential role of technologies based on gold nanoparticles (GNPs) has been evaluated. GNPs were synthesized by using a cysteine protease, sericin whose reducing properties were exploited to bioengineer NPs (SrGNPs) where sericin with the help of thiol groups encapsulated over the surface of GNPs. Further, SrGNPs were bioconjugated with levofloxacin (Levo) and balofloxacin (Balo) to increase the efficacy of these drugs. Here, the antibacterial action of SrGNPs and their bioconjugated counterparts comprising Levo (Levo-SrGNPs), Balo (Balo-SrGNPs), and Levo/Balo (Levo-Balo-SrGNPs) were examined against normal and multi-drug resistant (MDR) strains of E. coli and S. aureus. The minimum inhibitory concentration (MIC) of these bioconjugates against said bacteria were found less than their pure counterparts. Further, the synergistic role of SrGNPs in combination with Levo and Balo was also explained using Chou-Talalay (C-T) method. The synthesis and bioconjugation of SrGNPs were confirmed by UV-visible spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), and zeta-potential.

Tumor-targeted Drug Delivery by Nanocomposites.

BACKGROUND: Tumor-targeted delivery by nanoparticles is a great achievement towards the use of highly effective drug at very low doses. The conventional development of tumor-targeted delivery by nanoparticles is based on enhanced permeability and retention (EPR) effect and endocytosis based on receptor-mediated are very demanding due to the biological and natural complications of tumors as well as the restrictions on the design of the accurate nanoparticle delivery systems. METHODS: Different tumor environment stimuli are responsible for triggered multistage drug delivery systems (MSDDS) for tumor therapy and imaging. Physicochemical properties, such as size, hydrophobicity and potential transform by MSDDS because of the physiological blood circulation different, intracellular tumor environment. This system accomplishes tumor penetration, cellular uptake improved, discharge of drugs on accurate time, and endosomal discharge. RESULTS: Maximum drug delivery by MSDDS mechanism to target therapeutic cells and also tumor tissues and sub cellular organism. Poorly soluble compounds and bioavailability issues have been faced by pharmaceutical industries, which are resolved by nanoparticle formulation. CONCLUSION: In our review, we illustrate different types of triggered moods and stimuli of the tumor environment, which help in smart multistage drug delivery systems by nanoparticles, basically a multi-stimuli sensitive delivery system, and elaborate their function, effects, and diagnosis.

Cisplatin bioconjugated enzymatic GNPs amplify the effect of cisplatin with acquiescence.

Enzymatic gold nanoparticles (B-GNPs) have been synthesized using a natural anticancer agent bromelain (a cysteine protease) and these nanoparticles were used to bioconjugate Cisplatin (highly effective against osteosarcoma and lung cancer). Cisplatin bioconjugated bromelain encapsulated gold nanoparticles (B-C-GNPs) were found profoundly potent against same cancers at much lower concentration with minimum side effects due to the synergistic effect of bromelain. The B-C-GNPs have been observed to inhibit the proliferation of osteosarcoma cell lines Saos-2 and MG-63 with IC50 estimation of 4.51 µg/ml and 3.21 µg/ml, respectively, and against small lung cancer cell line A-549 with IC50 2.5 µg/ml which is lower than IC50 of cisplatin against same cell lines. The B-GNPs/B-C-GNPs were characterized by TEM, UV-Visible spectroscopy, Zeta potential and DLS to confirm the production, purity, crystalline nature, stability of nanoemulsion, size and shape distribution. The change in 2D and 3D conformation of bromelain after encapsulation was studied by Circular Dichroism and Fluorometry, respectively. It was found that after encapsulation, a 19.4% loss in secondary structure was observed, but tertiary structure was not altered significantly and this loss improved the anticancer activity. The confirmation of bioconjugation of cisplatin with B-GNPs was done by UV-Visible spectroscopy, TEM, FTIR, 2D 1H NMR DOSY and ICP-MS. Further, it was found that almost ~4 cisplatin molecules bound with each B-GNPs nanoparticle.

Biochemical synthesis of gold nanoparticles from leaf protein of Nicotiana tabacum L. cv. xanthi and their physiological, developmental, and ROS scavenging responses on tobacco plant under stress conditions.

The stress conditions imposed by the impact of metal and non-metal oxide nanoparticles over plant systems enhances the synthesis of reactive oxygen species (ROS), resulting in oxidative damage at cellular level. The objective of this study was to synthesise the gold nanoparticles (GNps) from the leaves protein of Nicotiana tabacum L. cv. xanthi, its characterisation, and response on plant physiology and ROS scavenging activity on plants after exposure to different stresses. The authors have treated N. tabacum L. cv. xanthi plants with 100, 200, 300, 400, and 500 ppm biochemically synthesised GNps and examined physiological as well as biochemical changes. Results showed that biochemically synthesised GNps exposure significantly increased the seed germination (P < 0.001), root (P < 0.001), shoot growth (P < 0.001), and antioxidant ability (P < 0.05) of plants depending on bioengineered GNPs concentrations. Low concentrations (200-300 ppm) of GNps boosted growth by ∼50% and significantly increase in photosynthetic parameters such as total chlorophyll content (P < 0.05), membrane ion leakage (P < 0.05) as well as malondialdehyde (P < 0.05) content with respect to untreated plants under stress conditions. The high concentration (400-500 ppm) of GNps affected these parameters in a negative manner. The total antioxidant activity was also elevated in the exposed plants in a dose-dependent manner.

Purification and characterization of a cystatin like thiol protease inhibitor from Brassica nigra.

Phytocystatins or plant cystatins belong to a group of thiol protease inhibitors present ubiquitously in living system. They play a crucial role in cellular protein turnover thereby showing involvement in a wide array of physiological processes in plants. With wide importance and tremendous potential applications in the fields of genetic engineering, medicine, agriculture, and food technology, it is imperative to identify and isolate such protease inhibitors from different cheap and easily available plant sources. Present study focuses on the isolation, purification and characterization of a cystatin like thiol protease inhibitor from the seeds of Brassica nigra (rai mustard) following a simple two-step method using ammonium sulphate fractionation (40-60%) and gel filtration chromatography on Sephacryl S-100HR column with 51.85% yield and 151.50 fold purification. Rai seed cystatin (RSC) gave a molecular mass of ~19.50 kDa as determined by SDS PAGE and gel filtration behaviour. Stokes radius and diffusion coefficient of RSC were 19.80 Šand 11.21 × 10-7 cm2 s-1 respectively. Kinetic analysis revealed a reversible and non-competitive mode of inhibition with RSC showing highest inhibition towards papain (Ki = 1.62 × 10-7 M) followed by ficin and bromelain. Purified RSC possessed an α helical content of 35.29% as observed by far-UV CD spectroscopy. UV, fluorescence, CD and FTIR spectral studies revealed a significant conformational alteration in one or both the proteins upon RSC-papain complex formation. Isothermal Titration Calorimetry (ITC) analysis further revealed the values for different thermodynamic parameters involved in complex formation, indicating the process to be enthalpically as well as entropically driven with forces involved in binding the proteins to be electrostatic in nature. Additionally binding stoichiometry (N) of 0.95 ±â€¯0.08 sites indicates that each molecule of RSC is surrounded by nearly one papain molecule.

Biogenic pentagonal silver nanoparticles for safer and more effective antibacterial therapeutics.

BACKGROUND: Biological synthesis of nanomaterials possesses unprecedented potential in the production of nanomaterials due to their ability to produce nanomaterials with improved biocompatibility in addition to eco-friendly synthetic procedures. METHODS: This article reports the isolation of an air-borne fungus from the campus of Integral University, Lucknow, with an exceptional ability to withstand very high concentrations of silver salt. The fungus was found to produce pentagonal silver nanoparticles (AgPgNps) when silver ions were reduced from silver nitrate. Molecular analysis and biochemical characterization techniques based on 18-seconds rRNA identified the fungus to belong to the Aspergillus sp. with the NCBI accession no KF913249. Material characterization techniques including ultraviolet (UV)-visible spectroscopy, transmission electron microscopy, and zeta potential analysis were used to satisfactorily characterize the as-synthesized AgPgNps. RESULTS: The AgPgNps synthesized by the fungus Aspergillus sp. exhibit an absorption that is maximum centered at about 416 nm, with a standard particle size of 23.22±2 nm. These AgPgNps exhibited broad-spectrum antimicrobial activities against an array of bacterial pathogens with remarkable minimum inhibitory concentration (MIC50) values: Staphylococcus aureus (ATCC 25923) - 9.230 µg/mL, Bacillus sp. (ATCC 14593) - 12.781 µg/mL, Escherichia coli (ATCC 25922) - 5.063 µg/mL, and Klebsiella pneumoniae (ATCC 13883) - 5.426 µg/mL. In vitro cytotoxicity analysis of biosynthesized AgPgNps showed a dose-response activity against human cervical cancer cell line (HeLa) and adenocarcinoma cells (A549) with MIC50 values of 0.038 µg/mL and 0.044 µg/mL, respectively. CONCLUSION: These findings are very crucial to evaluate the biosynthetic process for the synthesis of nanoparticles (NPs) with unique properties. These NPs may find potential applications in sensing, medicine, and antimicrobial and anticancer therapies.

The in vivo and in vitro approaches for establishing a link between advanced glycation end products and lung cancer.

Advanced glycation end products (AGEs) are directly related to third aging-associated diseases, such as cardiovascular diseases, arteriosclerosis, and neurodegeneration. Likewise, these irreversible and nonenzymatic products have been reported to be involved in the progression of malignant cancers. In general, aging-associated diseases and the initiation of cancer have been subjects of interest for several years. Few studies on the role of AGEs in cancer have been performed on cell lines. Moreover, past investigations in the field of glycation biology still lack the knowledge of in vivo and in vitro approaches for cancer cells. Accordingly, we aimed to focus on and establish a link between cancer and glycation with respect to all the possible AGEs. In our study, the levels of carboxymethyllysine (CML) increased by 50.94% in an animal model of glycation, whereas in an animal model of cancer, the contents of CML increased by 45.94% compared with their negative controls. Similarly, fluorescent AGEs were also examined and were found to be increased by 65.3% and 58.63% in the animal models of glycation and cancer, respectively, compared with the control subjects. The protein carbonyl contents were also found to be enhanced in the animal models of glycation and cancer. In our study, the levels of reactive oxygen species were also found to be significantly increased in the in vitro model of cancer cells as compared with the controls. Such an initial breakthrough indicated that AGEs were present in the serum of the animal models of cancer and glycation.

Do all roads lead to the Rome? The glycation perspective!

Oxidative, carbonyl, and glycative stress have gained substantial attention recently for their alleged influence on cancer progression. Oxidative stress can trigger variable transcription factors, such as nuclear factor erythroid-2-related factor (Nrf2), nuclear factor kappa B (NF-κB), protein-53 (p-53), activating protein-1 (AP-1), hypoxia-inducible factor-1α (HIF-1α), ß-catenin/Wnt and peroxisome proliferator-activated receptor-γ (PPAR-γ). Activated transcription factors can lead to approximately 500 different alterations in gene expression, and can alter expression patterns of inflammatory cytokines, growth factors, regulatory cell cycle molecules, and anti-inflammatory molecules. These alterations of gene expression can induce a normal cell to become a tumor cell. Glycative stress resulting from advanced glycation end products (AGEs) and reactive dicarbonyls can significantly affect cancer progression. AGEs are fashioned from the multifaceted chemical reaction of reducing sugars with a compound containing an amino group. AGEs bind to and trigger the receptor for AGEs (RAGE) through AGE-RAGE interaction, which is a major modulator of inflammation allied tumors. Dicarbonyls like, GO (glyoxal), MG (methylglyoxal) and 3-DG (3-deoxyglucosone) fashioned throughout lipid peroxidation, glycolysis, and protein degradation are viewed as key precursors of AGEs. These dicarbonyls lead to the carbonyl stress in living organisms, possibly resulting in carbonyl impairment of proteins, carbohydrates, DNA, and lipoproteins. The damage caused by carbonyls results in numerous lesions, some of which are involved in cancer pathogenesis. In this review, the effects of oxidative, carbonyl and glycative stress on cancer initiation and progression are thoroughly discussed, including probable signaling pathways and the effects on tumorigenesis.

Oxidation, glycation and glycoxidation-The vicious cycle and lung cancer.

The combine effect of oxidative and glycative stress predisposed to glycoxidation, and their outcomes that play critical role in lung cancer have been examined in different ways. The therapeutic approaches for lung cancer are still unsatisfactory. We observe some unclear and decisive pathways which might play an important role in targeting lung cancer. The roadmap of signaling pathway includes p38 MAPK, NF-ƙB, TNF-α and AGE-RAGE binding affinity play role in the cell growth, proliferation, apoptosis inhibition and metastasis. The goal of this review is to achieve a new signaling map inside the lung cancer which is mediated by glycoxidative products mainly reactive dicarbonyls and advanced glycation end products (AGEs). Additionally, AGE-RAGE binding critically regulates the suppression and promotion of lung cancer via inhibition and activation of different signaling pathways. Hence, this review suggests the role of oxidation, glycation, and glycoxidation in lung cancer.

Gold nanoconjugates reinforce the potency of conjugated cisplatin and doxorubicin.

Osteosarcoma or osteogenic sarcoma is the most common and prevalent cancerous tumor of bone and occurs especially in children and teens. Recent treatment strategy includes a combination of both chemotherapy and surgeries. Although, the use of single drug-based chemotherapy treatment remains unsatisfactory. Therefore, combinatorial therapy has emerged as a potential strategy for treatment with limited side- effects. Here, we evaluated the combinatorial anticancerous effect of cisplatin (CIS) and doxorubicin (DOX) bioconjugated bromelain encapsulated gold nanoparticles (B-AuNPs conjugated CIS and DOX) in the treatment of osteosarcoma. The synthesized B-AuNPs conjugated CIS and DOX were characterized by various characterization techniques like UV-vis spectroscopy, TEM, DLS and zeta potential to ensure the synthesis, size, shape, size distribution and stability. Drug loading efficiency bioconjugation of CIS and DOX was ensured by UV-vis spectroscopy. Bioconjugation of CIS and DOX was further confirmed using UV-vis spectroscopy, TEM, DLS, Zeta potential and FT-IR analysis. The combinatorial effect of CIS and DOX in B-AuNPs conjugated CIS and DOX showed highly improved potency against MG-63 and Saos-2 cells at a very low concentration where primary osteoblasts didn't show any cytotoxic effect. The apoptotic effect of B-AuNPs conjugated CIS and DOX on osteosarcoma and primary osteoblasts cells were analyzed by increased permeability of the cell membrane, condensed chromatin and deep blue fluorescent condensed nucleus. The results clearly showed that B-AuNPs conjugated CIS and DOX significantly improved the potency of both the chemotherapeutic drugs by delivering them specifically into the nucleus of cancer cells through caveolae-dependent endocytosis. Thus, the greater inhibitory effect of combinatorial drugs (B-AuNPs conjugated CIS and DOX) over single drug based chemotherapy would be of great advantage during osteosarcoma treatment.

Biogenic terbium oxide nanoparticles as the vanguard against osteosarcoma.

The synthesis of inner transition metal nanoparticles via an ecofriendly route is quite difficult. This study, for the first time, reports synthesis of terbium oxide nanoparticles using fungus, Fusarium oxysporum. The biocompatible terbium oxide nanoparticles (Tb2O3 NPs) were synthesized by incubating Tb4O7 with the biomass of fungus F. oxysporum. Multiple physical characterization techniques, such as UV-visible and photoluminescence spectroscopy, TEM, SAED, and zeta-potential were used to confirm the synthesis, purity, optical and surface characteristics, crystallinity, size, shape, distribution, and stability of the nanoemulsion of Tb2O3 NPs. The Tb2O3 NPs were found to inhibit the propagation of MG-63 and Saos-2 cell-lines (IC50 value of 0.102µg/mL) and remained non-toxic up to a concentration of 0.373µg/mL toward primary osteoblasts. Cell viability decreased in a concentration-dependent manner upon exposure to 10nm Tb2O3 NPs in the concentration range 0.023-0.373µg/mL. Cell toxicity was evaluated by observing changes in cell morphology, cell viability, oxidative stress parameters, and FACS analysis. Morphological examinations of cells revealed cell shrinkage, nuclear condensation, and formation of apoptotic bodies. The level of ROS within the cells-an indicator of oxidative stress was significantly increased. The induction of apoptosis at concentrations ≤IC50 was corroborated by 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) staining (DNA damage and nuclear fragmentation). Flow-cytometric studies indicated that the response was dose dependent with a threshold effect.