Chitosan/PLA-loaded Magnesium oxide nanocomposite to attenuate oxidative stress, neuroinflammation and neurotoxicity in rat models of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by amyloid-beta (Aß) aggregation, neuroinflammation, oxidative stress, and dysfunction in the mitochondria and cholinergic system. In this study, the synthesis of chitosan-polylactic acid-loaded magnesium oxide nanocomposite (CH/PLA/MgONCs) was examined using the green precipitation method. The synthesized CH/PLA/MgONCs were confirmed by using the UV-Vis spectrum, FT-IR, SEM-EDAX, and physical properties. The experiments were carried out using male Wistar rats by injecting streptozotocin (STZ) bilaterally into the brain's ventricles through the intracerebroventricular (ICV) route at a dose of 3 mg/kg. We also evaluated the effects of CH/PLA/MgONCs at doses of 10 mg/kg. To assess the cognitive dysfunction induced by ICV-STZ, we performed behavioral, biochemical, and histopathological analyses. In our study results, UV-Vis spectrum analysis of CH/PLA/MgONCs showed 285 nm, FT-IR analyses confirmed that the various functional groups were present, and SEM-EDAX analysis confirmed that a cauliflower-like spherical shape, Mg and O were present. Treatment with CH/PLA/MgONCs (10 mg/kg) showed a significant improvement in spatial and non-spatial memory functions. This was further supported by biochemical analysis showing improved antioxidant enzyme (GSH, SOD, CAT, and GPx activity) activities that significantly attenuated cholinergic activity and oxidative stress. In the CH/PLA/MgONCs-treated group, significant improvement was observed in the mitochondrial complex activity. ICV-STZ-induced neuroinflammation, as indicated by increased levels of TNF-α, IL-6, and CRP, was significantly reduced by CH/PLA/MgONCs treatment. Additionally, CH/PLA/MgONCs treated histological results showed improved healthy neuronal cells in the brain. Furthermore, in silico studies confirm that these molecules have good binding affinity and inhibit Aß aggregation. In conclusion, CH/PLA/MgONCs treatment reversed AD pathology by improving memory and reducing oxidative stress, neuroinflammation, and mitochondrial dysfunction. These findings recommend that CH/PLA/MgONCs are possible therapeutic agents to treat AD.

Gelatin/polyethylene glycol-loaded magnesium hydroxide nanocomposite to attenuate acetylcholinesterase, neurotoxicity, and activation of GPR55 protein in rat models of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative disease marked by mitochondrial dysfunction, amyloid-ß (Aß) aggregation, and neuronal cell loss. G-protein-coupled receptor 55 (GPR55) has been used as a promising target for insulin receptors in diabetes therapy, but GPR55's role in AD is still unidentified. Gelatin (GE) and polyethylene glycol (PEG) polymeric hydrogels are commonly used in the drug delivery system. Therefore, the aim of the present study was the preparation of magnesium hydroxide nanocomposite using Clitoria ternatea (CT) flower extract, GE, and PEG (GE/PEG/Mg(OH)2NCs) by the green precipitation method. The synthesized GE/PEG/Mg(OH)2NCs were used to determine the effect of GPR55 activation of intracerebroventricular administration on streptozotocin (ICV-STC)-induced cholinergic dysfunction, oxidative stress, neuroinflammation, and cognitive deficits. The GE/PEG/Mg(OH)2NCs were administered following bilateral ICV-STC administration (3 mg/kg) in experimental rats. Neurobehavioral assessments were performed using a Morris water maze (MWM) and a passive avoidance test (PA). Cholinergic and antioxidant activity, oxidative stress, and mitochondrial complex activity were estimated in the cortex and hippocampus through biochemical analysis. Inflammatory markers (TNF-α, IL-6, and IL-1ß) were determined using the ELISA method. Our study results demonstrated that the GE/PEG/Mg(OH)2NCs treatment significantly improved spatial and non-spatial memory functions in behavioral studies. Moreover, the treatment with GE/PEG/Mg(OH)2NCs group significantly attenuated cholinergic dysfunction, oxidative stress, and inflammatory markers, and also highly improved anti-oxidant activity (GSH, SOD, CAT, and GPx) in the cortex and hippocampus regions. The western blot results suggest the activation of the GPR55 protein expression through GE/PEG/Mg(OH)2NCs. The histopathological studies showed clear cytoplasm and healthy neurons, effectively promoting neuronal activity. Furthermore, the molecular docking results demonstrated the binding affinity and potential interactions of the compounds with the AChE enzyme. In conclusion, the GE/PEG/Mg(OH)2NCs treated groups showed reduced neurotoxicity and have the potential as a therapeutic agent to effectively target AD.

Gelatin/polyvinyl alcohol loaded magnesium hydroxide nanocomposite attenuates neurotoxicity and oxidative stress in Alzheimer's disease induced rats.

Amyloid-ß (Aß) plaque formation, neuronal cell death, mitochondrial and cholinergic dysfunction are key indicators of Alzheimer's disease (AD). In this study, gelatin and polyvinyl alcohol (PVA) were tethered with magnesium hydroxide (Mg(OH)2) to synthesize nanocomposite (Ge/PVA/Mg(OH)2) through alkali co-precipitation. The characterization studies using FT-IR, XRD, DLS, and SEM-EDX confirmed the successful formation of Ge/PVA/Mg(OH)2 nanocomposite. Further, in vitro study it clearly demonstrated the impact of Ge/PVA/Mg(OH)2 nanocomposite on biocompatibility, cellular uptake, reduced Aß protein expression and protection of neuronal cell death. The confocal study further confirmed the down-regulation of Aß expression. The subsequent in vivo analysis witnessed the protective effect of Ge/PVA/Mg(OH)2 nanocomposites on the cognitive and synaptic impairments of AD in intraceribroventricular streptozotocin (ICV-STZ) treated rats. Oxidative stress, antioxidant enzymes, cholinergic and mitochondrial complex activity were conducted and revealed that the Acetylcholineesterase (AChE) and Malondialdehyde (MDA) activities were significantly decreased by contrast the antioxidant enzyme activities were found to be increased in the cortex and hippocampus regions of the brain. Thus, the present investigation recommends Ge/PVA/Mg(OH)2 nanocomposite to target AD and clinical translation.

Phyto-drug conjugated nanomaterials enhance apoptotic activity in cancer.

Cancer continues to be one of the leading causes of death worldwide and is a major obstacle to increased life expectancy. However, survival has not improved significantly with average cancer standard treatment strategies over the past few decades; survival rates have remained low, with tumor metastasis, adverse drug reactions, and drug resistance. Therefore, substitute therapies are essential to treat this dreadful disease. Recently, research has shown that natural compounds in plants, such as phytochemicals, are extensively exploited for their anticarcinogenic potential. Phytochemicals may show their anticancer activity different cancer cell markers may alter molecular pathways, which promote in cellular events such as cell cycle arrest and apoptosis, regulate antioxidant status, cell proliferation, migration, invasion and toxicity. Although their outstanding anticancer activity, however, their pharmacological budding is hindered by their low aqueous solubility, poor bioavailability, and poor penetration into cells, hepatic disposition, narrow therapeutic index, and rapid uptake by normal tissues. In this situation, nanotechnology has developed novel inventions to increase the potential use of phytochemicals in anticancer therapy. Nanoparticles can improve the solubility and stability of phytochemicals, specific tumor cell/tissue targeting, enhanced cellular uptake, reduction of phytochemicals. Therapeutic doses of phytochemicals for a long time. Additional benefits include better blood stability, multifunctional design of nanocarriers and improvement in countermeasures. This review summarizes the advances in the use of nanoparticles for the treatment of cancer, as well as various nano-drug deliveries of phytochemicals against cancer. In particular, we are introducing several applications of nanoparticles in combination with phyto-drug for the treatment of cancer.

Mitochondrial dysfunction-induced apoptosis in breast carcinoma cells through a pH-dependent intracellular quercetin NDDS of PVPylated-TiO2NPs.

In this article, we report the validation of cancer nanotherapy for the treatment of cancers using quercetin (Qtn). Much attention has been paid to the use of nanoparticles (NPs) to deliver drugs of interest in vitro/in vivo. Highly developed NPs-based nano drug delivery systems (NDDS) are an attractive approach to target cancer cell apoptosis, which is related to the onset and progression of cancer. Conventional chemotherapy has some notable drawbacks, such as lack of specificity, requirement of high drug doses, adverse effects, and gradual development of multidrug resistance (MDR), that decrease the efficacy of cancer therapy. To overcome these challenges of chemotherapy, the achievement of high drug loading in combination with low leakage at physiological pH, minimal toxicity toward healthy cells, and tunable controlled release at the site of action is an ongoing challenge. To assist drug delivery, we have prepared PVPylated-TiO2NPs containing Qtn with high loading efficiency (26.6% w/w) as a NDDS. The Qtn-PVPylated-TiO2NPs are uptaken via endocytosis by cancer cells and can generate intracellular reactive oxygen species (ROS) in order to increase mitochondrial membrane potential loss (Δψm) and enable release of cytochrome-c, followed by dysregulation of Bcl-2 into the cytosol and activation of caspase-3 to induce cancer cell apoptosis. These novel nanocombinations can be utilized to improve cancer nanotherapy by induction of apoptosis in vitro. Analysis at the molecular level revealed that the Qtn-PVPylated-TiO2NPs nanocombinations induced Δψm-mediated apoptotic signaling pathways. Overall, this study demonstrated that careful design of non-toxic nanocarriers for cancer nanotherapy can yield affordable NDDS.

Correction: Mitochondrial dysfunction-induced apoptosis in breast carcinoma cells through a pH-dependent intracellular quercetin NDDS of PVPylated-TiO2NPs.

Correction for 'Mitochondrial dysfunction-induced apoptosis in breast carcinoma cells through a pH-dependent intracellular quercetin NDDS of PVPylated-TiO2NPs' by Thondhi Ponraj et al., J. Mater. Chem. B, 2018, 6, 3555-3570.

Synergistic effect of chemo-photothermal for breast cancer therapy using folic acid (FA) modified zinc oxide nanosheet.

Modern therapies for malignant breast cancer in clinics are not efficacious and often result in deprived patient compliance owing to squat therapeutic effectiveness and strong systemic side effects. In order to overcome this, we combined chemo-photothermal targeted therapy of breast cancer within one novel multifunctional drug delivery system. Folic Acid-functionalized polyethylene glycol coated Zinc Oxide nanosheet (FA-PEG-ZnO NS), was successfully synthesized, characterized and introduced to the drug delivery field for the first time. A doxorubicin (DOX)-loaded FA-PEG-ZnO NS based system (DOX-FA-PEG-ZnO NS) showed stimulative effect of heat, pH responsive and sustained drug release properties. Cytotoxicity experiments confirmed that combined therapy mediated the maximum rate of death in breast cancer cells compared to that of single chemotherapy or photothermal therapy. In vivo toxicity evaluation showed that the DOX-FA-PEG-ZnO NS contains minimum systemic toxicity in the mice model system. The findings of the present study provided an ideal drug delivery system for breast cancer therapy due to the advanced chemo-photothermal synergistic targeted therapy and good drug release properties of DOX-FA-PEG-ZnO NS, which could effectively avoid frequent and invasive dosing and improve patient compliance. Thus, functionalized-ZnO NS could be used as a novel nanomaterial for selective chemo-photothermal therapy.

Protein regulation and Apoptotic induction in human breast carcinoma cells (MCF-7) through lectin from G. beauts.

Lectins are proteins that show a variety of biological activities. Nevertheless, information on lectin from Gluttonous beauts and their anticancer activities are very limited. In this study, we purified a lectin from hemolymph of G. beauts and identified its molecular weight to be 66kDa. The effect of lectin at different concentrations (µg/mL) on the cell growth and apoptosis were evaluated against MCF-7 and MCF-10A cells, whereas cytotoxicity to the MCF-7 cells mediated by lectin was observed and the mechanism of action of the lectin in including apoptosis in cancer cells via the intrinsic pathway was also proposed. The MCF-7 cells were employed for in vitro studies on cytotoxicity, induction of apoptosis and apoptotic DNA fragmentation. In MCF-10A cells lectin did not show any adverse effect even at higher concentration. Cell cycle analysis also showed a significant cell cycle arrest on selected cells after lectin treatment. Western blotting suggested that lectin up regulates the apoptotic protein expression in MCF-7 cells while it down regulates the level of Bcl-2 expression.

Dietary supplementation of green synthesized manganese-oxide nanoparticles and its effect on growth performance, muscle composition and digestive enzyme activities of the giant freshwater prawn Macrobrachium rosenbergii.

The green synthesized Mn3O4 nanoparticles (manganese-oxide nanoparticles) using Ananas comosus (L.) peel extract was characterized by various techniques. HR-SEM photograph showed that manganese-oxide nanoparticles (Mn-oxide NPs) were spherical in shape, with an average size of 40-50 nm. The Zeta potential revealed the surface charge of Mn-oxide NPs to be negative. Further, the Mn-oxide NPs were dietary supplemented for freshwater prawn Macrobrachium rosenbergii. The experimental basal diets were supplemented with Mn-oxide NPs at the rates of 0 (control), 3.0, 6.0, 9.0, 12, 15 and 18 mg/kg dry feed weight. The as-supplemented Mn-oxide NPs were fed in M. rosenbergii for a period of 90 days. The experimental study demonstrated that prawns fed with diet supplemented with 3-18 mg Mn-oxide NPs/kg shows enhanced (P<0.05) growth performance, including final weight and weight gain (WG). Significant differences (P<0.05) in feed conversion ratio (FCR) were observed in prawn fed with different diets. Additionally, prawns fed with 3.0-18 mg/kg Mn-oxide NPs supplemented diets achieved significant (P<0.05) improvement in growth performance, digestive enzyme activities and muscle biochemical compositions, while, the prawns fed with 16 mg/kg of Mn-oxide NPs showed enhanced performance. Prawns fed on diet supplemented with 16 mg/kg Mn-oxide NPs showed significantly (P<0.05) higher total protein level. The antioxidants enzymatic activity (SOD and CAT) metabolic enzymes status in muscle and hepatopancreas showed no significant (P>0.05) alterations in prawns fed with 3.0-18 mg/kg of Mn-oxide NPs supplemented diets. Consequently, the present work proposed that 16 mg/kg of Mn-oxide NPs could be supplemented for flexible enhanced survival, growth and production of M. rosenbergii. Therefore, the data of the present study recommend the addition of 16 mg/kg of Mn-oxide NPs diet to developed prawn growth and antioxidant defense system.

Ligand-conjugated mesoporous silica nanorattles based on enzyme targeted prodrug delivery system for effective lung cancer therapy.

Epidermal growth factor receptor antibody (EGFRAb) conjugated silica nanorattles (SNs) were synthesized and used to develop receptor mediated endocytosis for targeted drug delivery strategies for cancer therapy. The present study determined that the rate of internalization of silica nanorattles was found to be high in lung cancer cells when compared with the normal lung cells. EGFRAb can specifically bind to EGFR, a receptor that is highly expressed in lung cancer cells, but is expressed at low levels in other normal cells. Furthermore, in vitro studies clearly substantiated that the cPLA2α activity, arachidonic acid release and cell proliferation were considerably reduced by pyrrolidine-2 loaded EGFRAb-SN in H460 cells. The cytotoxicity, cell cycle arrest and apoptosis were significantly induced by the treatment of pyrrolidine-2 loaded EGFRAb-SN when compared with free pyrrolidine-2 and pyrrolidine-2 loaded SNs in human non-small cell lung cancer cells. An in vivo toxicity assessment showed that silica nanorattles and EGFRAb-SN-pyrrolidine-2 exhibited low systemic toxicity in healthy Balb/c mice. The EGFRAb-SN-pyrrolidine-2 showed a much better antitumor activity (38%) with enhanced tumor inhibition rate than the pyrrolidine-2 on the non-small cell lung carcinoma subcutaneous model. Thus, the present findings validated the low toxicity and high therapeutic potentials of EGFRAb-SN-pyrrolidine-2, which may provide a convincing evidence of the silica nanorattles as new potential carriers for targeted drug delivery systems.

Curtailing overexpression of E2F3 in breast cancer using siRNA (E2F3)-based gene silencing.

BACKGROUND AND AIMS: The E2F3 transcription factor claims its role in controlling cell cycle progression. As reported earlier, nuclear E2F3 overexpression leads to development of bladder and prostate cancer in humans. Accordingly, the present investigation has been designed to assess to what extent E2F3 would be overexpressed in breast cancer. The aim of this study was to emphasize that the levels of E2F3 are increased in breast cancer and highlights the efficacy of siRNA targeted to E2F3. METHODS: To investigate the expression level of E2F3 and the progression of breast tumors, quantitative real-time PCR analysis was carried out. Western blotting analysis was performed to measure its counterparts, namely, E2F3a and E2F3b. RESULTS: In the novel axis of E2F3, a large set of 11 breast cancer cell lines were identified to have the property of overexpression. Furthermore, the small interfering RNA (siRNA) developed against E2F3 significantly blocked the expression of the E2F3 in the selected breast cancer cell lines. Thus, the present findings authenticate the efficiency of siRNA (E2F3) to fight against breast cancer; hence, the siRNA mediated E2F3 gene silencing knockdown the E2F3. CONCLUSIONS: This in vitro study demonstrates that E2F3 is a newly identified diagnostic and potential therapeutic target in breast cancer. Outcomes of this study affirm that siRNA for E2F3 facilitates the silencing of E2F3 overexpression and fights against breast cancer. Therefore, it plays a vital role as an alternative for diagnosis and clinical outcome for the treatment of breast cancer.