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.

Voglibose attenuates cognitive impairment, Aß aggregation, oxidative stress, and neuroinflammation in streptozotocin-induced Alzheimer's disease rat model.

Alzheimer's disease (AD) is an age-dependent neurodegenerative disease hallmarked by Amyloid-ß (Aß) aggregation, cognitive impairment, and neuronal and synaptic loss. In this study, AD was induced in male Wistar rats (n = 6) by the administration of intracerebroventricular-streptozotocin (ICV-STZ-3 mg/kg/day), and Voglibose (Vog) was administered at various doses (10, 25, and 50 mg/kg), while Galantamine (3 mg/kg) acted as a reference standard drug. Behavioral alterations in both spatial and non-spatial memory functions were evaluated in the experimental rats. At the end of the study, all experimental rats were sacrificed, and their brain parts, the cortex and hippocampus, were subjected to biochemical, western blot, and histopathological analysis. In our study results, the statistically significant dose-dependent results from the behavioral tests show the Voglibose-treated groups significantly improved (p < 0.0001) spatial and non-spatial memory functions when compared with ICV-STZ-treated group. Meanwhile, when compared with ICV-STZ-treated rats, treatment with Voglibose (10, 25, and 50 mg/kg) showed the activities of both acetylcholinesterase (AChE) and malondialdehyde (MDA) were significantly attenuated (p < 0.0001), while the operation of antioxidant enzymes was considerably enhanced (p < 0.0001). The molecular estimation showed that it significantly attenuates (p < 0.0001) the TNF-α, IL-1ß, and CRP activity, and the western blot results demonstrate the significantly attenuated Aß aggregation. The histopathological results showed that the Voglibose treatment had an effective improvement in clear cytoplasm and healthy neuronal cells. In conclusion, our results suggest that Voglibose has potent neuroprotective effects against the ICV-STZ-induced AD model. Furthermore, these results support the possibility of Voglibose as a therapeutic approach to improving cognitive function, suggesting that controlling Aß aggregation might be a novel target for the development of 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.

Galantamine tethered hydrogel as a novel therapeutic target for streptozotocin-induced Alzheimer's disease in Wistar rats.

Amyloid-ß (Aß) plaque formation, neuronal cell death, and cognitive impairment are the unique symptoms of Alzheimer's disease (AD). No single step remedy is available to treat AD, so the present study aimed to improve the drugability and minimize the abnormal behavioral and biochemical activities in streptozotocin (STZ) induced AD experimental Wistar rats. In particular, we explored the utilization of methacrylated gelatin (GelMA), which is a biopolymeric hydrogel that mimics the natural tissue environment. The synthesized biopolymeric gel contained the drug galantamine (Gal). Investigations were conducted to evaluate the behavioral activities of STZ-induced AD experimental rats under STZ â€‹+ â€‹GelMA â€‹+ â€‹Gal treatment. The experimental groups comprised the control and STZ, STZ â€‹+ â€‹GelMA, STZ â€‹+ â€‹Gal, and STZ â€‹+ â€‹GelMA â€‹+ â€‹Gal (10 â€‹mg/kg) treated rats. Intracerebroventricular STZ ensures cognitive decline in terms of an increase in the escape latency period, with a decrease in the spontaneous alteration of behavioral activities. Our results indicated decrease Aß aggregation in the hydrogel-based drug treatment group and significant decreases in the levels of acetylcholinesterase and lipid peroxidation (p â€‹< â€‹0.001). In addition, the glutathione and superoxide dismutase activities appeared to be improved in the STZ â€‹+ â€‹GelMA â€‹+ â€‹Gal group compared with the other treatment groups. Furthermore, histopathological and immunohistochemical experiments showed that the GelMA â€‹+ â€‹Gal treated AD rats exhibited significantly improved behavioral and biochemical activities compared with the STZ treated AD rats. Therefore, STZ â€‹+ â€‹GelMA â€‹+ â€‹Gal administration from the pre-plaque stage may have a potential clinical application in the prevention of AD. Thus, we conclude that hydrogel-based Gal drugs are efficient at decreasing Aß aggregation and improving the neuroinflammatory process, antioxidant activity, and neuronal growth.

Vermiremediation of engine oil contaminated soil employing indigenous earthworms, Drawida modesta and Lampito mauritii.

Engine oil consists of hazardous substances that adversely affect the environment and soil quality. Bioremediation (employing organisms) is an appropriate technique to mitigate engine oil pollution. In the present study, the earthworm species, Drawida modesta (epigeic) and Lampito mauritii (anecic) were used to restore the soil polluted with polycyclic aromatic hydrocarbons (PAHs) and total petroleum hydrocarbons (TPHs) from used engine oil. Four treatments were set up in addition to positive and negative controls. A maximum of 68.6% PAHs and 34.3% TPHs removal in the treatment with soil (1 kg), cow dung (50 g), used engine oil (7.5 mL) and earthworms was recorded after 60 days. Undoubtedly, earthworms effectively removed PAHs and TPHs from the oil-contaminated soil. PAHs were more strongly accumulated in D. modesta (16.25 mg kg-1) than in L. mauritii (13.25 mg kg-1). Further, histological analysis revealed the epidermal surface irregularity, cellular disintegration, and cellular debris in earthworms. The pH (6.3%), electrical conductivity (12.7%), and total organic carbon (35.4%) were significantly (at P < 0.05) decreased after 60 days; while, total nitrogen (62%), total potassium (76.2%), and total phosphorus (19.2%) were substantially increased at the end of the experiment. The seed germination assay with fenugreek indicates that germination percentage (95%), and germination index (179), were dramatically increased in earthworm inoculated treatments when compared to the negative control (without earthworms). The results reveal that there is a great scope for utilizing the earthworms, D. modesta and L. mauritii for the bioremediation of soils contaminated with PAHs and TPHs.

Label-Free Electrochemical Detection of the Cancer Biomarker Platelet-Derived Growth Factor Receptor in Human Serum and Cancer Cells.

Overexpression of the platelet-derived growth factor receptor (PDGFR) was already associated with the loss of p53 function as cancer progresses in lung, breast, and cervical cancers. Cancer biomarker detection has faced challenges and barriers due to various limitations, including a high limit of detection, low sensitivity, time-consuming techniques, and expensive equipment. Hence, the present investigation is designed to develop a cost-effective novel biosensor based on a charge-based affinity bait molecule to detect the PDGFR, thus overcoming the limitations and challenges with an immune technique based on antigen-antibody interactions. We employed EDC-NHS coupling between poly (diallyl dimethylammonium chloride) and poly(acrylic acid) to attach the multiwall carbon nanotube surface. As a result, we performed electrochemical PDGFR conversion sensing with a dynamic range of 1-10,000 ng/mL and a detection limit of 1.5 pg/mL, which is comparable to the best current results. The biosensor also displayed good selectivity, 2.51% repeatability (RSD, n = 5), and 30 days of stability. Our study provides a pathway for the design of diagnostic interfaces in biosystems, as well as the emergence of new sensor types based on ligand-receptor interactions.

Activation of biochar through exoenzymes prompted by earthworms for vermibiochar production: A viable resource recovery option for heavy metal contaminated soils and water.

The industrial revolution and indiscriminate usage of a wide spectrum of agrochemicals account for the dumping of heavy metals in the environment. In-situ/ex-situ physical, chemical, and bioremediation strategies with pros and cons have been adopted for recovering metal contaminated soils and water. Therefore, there is an urgent requirement for a cost-effective and environment-friendly technique to combat metal pollution. Biochar combined with earthworms and vermifiltration is a suitable emerging technique for the remediation of metal-polluted soils and water. The chemical substances (e.g., sodium hydroxide, zinc chloride, potassium hydroxide, and phosphoric acid) have been used to activate biochar, which also faces several shortcomings. Studies reveal that extracellular enzymes have been used to activate biochar which is produced by earthworms and microbes that can alter the surface of the biochar. The present review focuses on the global scenario of metal pollution and its remediation through biochar activation using earthworms. The earthworms and biochar can produce "vermibiochar" which is capable of reducing the metal ions from contaminated water and soils. The vermifiltration can be a suitable technology for metal removal from wastewater/effluent. Thus, the biochar has a trick of producing entirely new options at a time when vermifiltration and other technologies are least expected. Further attention to the biochar-assisted vermifiltration of different sources of wastewater is required to be explored for the large-scale utilization of the process.

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.

Metallothionein dependent-detoxification of heavy metals in the agricultural field soil of industrial area: Earthworm as field experimental model system.

Earthworms are known to reclaim soil contamination and maintain soil health. In the present study, the concentration of DTPA extractable heavy metals, Cd, Cu, Cr, Pb, and Zn in vermicasts and tissues of the earthworms (anecic: Lampito mauritii; epigeic: Drawida sulcata) collected from the soils of four different industrial sites, Site-I (Sago industry), Site-II (Chemplast industry), Site-III (Dairy industry) and Site-IV (Dye industry) have been studied. The heavy metals in industrial soils recorded were 0.01-326.42 mg kg-1 with higher Cu, Cr, and Zn contents while the vermicasts showed lower heavy metal loads with improved physicochemical properties and elevated humic substances. The higher humic substances dramatically decreased the heavy metals in the soil. The bioaccumulation factors of heavy metals (mg kg-1) are in the order: Zn (54.50) > Cu (17.43) > Cr (4.54) > Pb (2.24) > Cd (2.12). The greatest amount of metallothionein protein (nmol g-1) was recorded in earthworms from Site-IV (386.76) followed by Site-III (322.14), Site-II (245.82), and Site-I (232.21). Drawida sulcata can produce a considerable amount of metallothionein protein than Lampito mauritii as the metallothionein production is dependent upon the presence of pollutants. The molecular docking analysis indicates a binding score of 980 for Cd, Cr and Cu, and 372 for Zn. Pb may bind with a non-metallothionein protein of earthworms and bio-accumulated in the internal chloragogenous tissues. Metallothionein neutralizes the metal toxicity and controls the ingestion of essential elements.

Environment-friendly management of textile mill wastewater sludge using epigeic earthworms: Bioaccumulation of heavy metals and metallothionein production.

In the present study, Eudrilus eugeniae and Perionyx excavatus were used for vermistabilization of textile mill sludge in different combinations with cowdung for 60 days. A higher percentage of metal removal was observed in earthworm treated mixtures for cadmium (54.5%) followed by copper (36.0%), chromium (37.0%) and zinc (35.9%). Vermistabilized textile mill sludge + cowdung (1:1) showed a maximum percentage increase in total NPK, a significant (P < 0.05) increase in bacteria, fungi, and actinomycetes with a better earthworm survival rate. A higher amount of metallothionein protein was produced by E. eugeniae than P. excavatus. Further, 100% textile mill sludge showed a number of histological abnormalities like degeneration of cells, cellular debris, and uneven cellular compartmentation while textile mill sludge with cowdung showed normal earthworm histology. Results suggest that textile mill sludge + cowdung (1:1) combination is suitable for vermistabilization of textile mill sludge.

Induction of intrinsic apoptotic signaling pathway in A549 lung cancer cells using silver nanoparticles from Gossypium hirsutum and evaluation of in vivo toxicity.

In the past decade, the research communities raised wide concerns on using medicinal plants for synthesis of nanomaterials due to its effective biological activity, lower side effects and also eco-friendly manner. Our previous report concentrated on the biomedical efficacy of fine characterized silver nanoparticles (AgNPs) from Gossypium hirsutum (cotton) leaf extract. Further, the current examination is planned to reveal the molecular mechanisms involving for activation of mitochondria-mediated signaling pathway by AgNPs in human lung cancer cells (A549) using various biological endpoints such as apoptotic induction by HOECHST 33342, AO/EtBr and Rhodamine 123 staining, cell cycle analysis using flow cytometry, gene and protein expressions by RT-PCR and immunoblotting respectively. This study was further extended to identify the toxicity of AgNPs using an animal model. Interestingly, we observed that A549 cells treated with AgNPs resulted in G2/M arrest and ultimately leads to induction of apoptosis cell death. Moreover, gene analysis demonstrated that diminished expression of anti-apoptotic (Bcl-2) and enhanced expression of pro-apoptotic (Bax) mitochondrial genes. The alterations in the gene pattern may interrupt of mitochondrial membrane potential which facilitates the releasing of cytochrome c (cyt c) into cytosol. The cyt c act as a key molecule for activation of caspases (9 and 3) to initiate intrinsic apoptotic signaling cell death process. The histological analysis proven the application of AgNPs in nanomedicine is quietly harmless and would not cause any discernible stress like swelling and inflammation to the organs of mice. Taken together, this investigation may provide solid evidence for cotton crop mediated AgNPs induced apoptosis cell death pathway and offer a novel approach for cancer therapy.

Gelatin-polysaccharide composite scaffolds for 3D cell culture and tissue engineering: Towards natural therapeutics.

Gelatin is a promising material as scaffold with therapeutic and regenerative characteristics due to its chemical similarities to the extracellular matrix (ECM) in the native tissues, biocompatibility, biodegradability, low antigenicity, cost-effectiveness, abundance, and accessible functional groups that allow facile chemical modifications with other biomaterials or biomolecules. Despite the advantages of gelatin, poor mechanical properties, sensitivity to enzymatic degradation, high viscosity, and reduced solubility in concentrated aqueous media have limited its applications and encouraged the development of gelatin-based composite hydrogels. The drawbacks of gelatin may be surmounted by synergistically combining it with a wide range of polysaccharides. The addition of polysaccharides to gelatin is advantageous in mimicking the ECM, which largely contains proteoglycans or glycoproteins. Moreover, gelatin-polysaccharide biomaterials benefit from mechanical resilience, high stability, low thermal expansion, improved hydrophilicity, biocompatibility, antimicrobial and anti-inflammatory properties, and wound healing potential. Here, we discuss how combining gelatin and polysaccharides provides a promising approach for developing superior therapeutic biomaterials. We review gelatin-polysaccharides scaffolds and their applications in cell culture and tissue engineering, providing an outlook for the future of this family of biomaterials as advanced natural therapeutics.

Drug-Carrying Capacity and Anticancer Effect of the Folic Acid- and Berberine-Loaded Silver Nanomaterial To Regulate the AKT-ERK Pathway in Breast Cancer.

Currently, in clinics, breast cancer is treated with free chemotherapeutic drugs, as a result there is not much therapeutic effect in treated models, leading to substantial systemic toxicity. To overcome these critical problems for the primary outcome, we developed the formulated nanomaterial (FA-PEG@BBR-AgNPs) aimed to specifically target cancer cells via nanoscopic-based drug delivery for getting better therapeutic effectiveness. In the present study, an isoquinoline alkaloid, berberine (BBR), was chosen as a cancer therapeutic agent, encapsulated on citrate-capped silver nanoparticles (AgNPs) through electrostatic interactions (BBR-AgNPs). Then, BBR-AgNPs were conjugated with polyethylene glycol-functionalized folic acid (FA-PEG) via hydrogen bonding interactions (FA-PEG@BBR-AgNPs). The transmission electron microscopy study shows the cellular invasion of the formulated FA-PEG@BBR-AgNPs, indicating the accretion of the nanomaterial at the tumor-specific site. Hence, FA conjugated with the nanomaterial suggests an efficient release of BBR molecules into the specific cancer site. Consequently, the results showed an increase in apoptotic induction via reactive oxygen species and condensed nuclei in cancer cells. Moreover, the western blotting analysis shows reduced/increased expression of PI3K, AKT, Ras, Raf, ERK, VEGF, HIF1α, Bcl-2, Bax, cytochrome c, caspase-9, and caspase-3, thereby enhancing apoptosis. Likewise, the in vivo antitumor efficiency of FA-PEG@BBR-AgNPs showed a significant restraint of tumor progression, and histopathological observations of lung, liver, kidney, heart, and brain tissues proved lesser toxicity of FA-PEG@BBR-AgNPs. Thus, the successfully formulated nanomaterial can serve as a potential drug-discharging vehicle to combat cancer cells by a molecular-based targeting approach.

Multifunctional nanoparticles for trimodal photodynamic therapy-mediated photothermal and chemotherapeutic effects.

Herein, we posit a biocompatible and pH-switchable integrated nano-delivery of CBP/ICG to the in vitro and in vivo experiments demonstrate that nanoparticles (NPs) have insignificant toxicity and good biocompatibility, and possess excellent tumor targeting efficiency as evidenced by highly efficient tumor ablation under near -infrared (NIR) illumination. In addition, we have conjugated folic acid as a targeting ligand for folate receptor-targeted delivery. Particularly, targeted delivery of dual CBP/ICG loaded NPs provide targeted detection and transporting potential to specific receptor-expressing tumors, and then CBP interfering with DNA damage and ICG generates singlet oxygen as well as photothermal heat when irradiated with NIR for simultaneous trimodal PDT/PTT/Chemotherapy. Using an animal model, a dramatic reduction in tumor growth without any evidence of significant long-term toxicity to organs after administration of NPs for trimodal therapy subjecting to NIR illumination. Thus, the in vivo satisfactory antitumor trimodal combined efficacy concurrent with complete tumor eradication and promising potential for advanced clinical phototherapy.

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.