Nanoparticle-mediated immunogenic cell death for cancer immunotherapy.

The field of cancer therapy is witnessing the emergence of immunotherapy, an innovative approach that activates the body own immune system to combat cancer. Immunogenic cell death (ICD) has emerged as a prominent research focus in the field of cancer immunotherapy, attracting significant attention in recent years. The activation of ICD can induce the release of damage-associated molecular patterns (DAMPs), such as calreticulin (CRT), adenosine triphosphate (ATP), high mobility group box protein 1 (HMGB1), and heat shock proteins (HSP). Subsequently, this process promotes the maturation of innate immune cells, including dendritic cells (DCs), thereby triggering a T cell-mediated anti-tumor immune response. The activation of the ICD ultimately leads to the development of long-lasting immune responses against tumors. Studies have demonstrated that partial therapeutic approaches, such as chemotherapy with doxorubicin, specific forms of radiotherapy, and phototherapy, can induce the generation of ICD. The main focus of this article is to discuss and review the therapeutic methods triggered by nanoparticles for ICD, while briefly outlining their anti-tumor mechanism. The objective is to provide a comprehensive reference for the widespread application of ICD.

Dietary nano-Selenium supplementation improves growth performance, nutrient digestibility and hematology in Cirrhinus mrigala fingerlings.

The following investigation was carried out to determine the effects of Selenium nanoparticles (Se NPs) on the growth rates, nutrient digestibility, and hematology of Cirrhinus mrigala fingerlings fed sunflower meal as basal diet. The experiment included seven test diets with varying Se levels (0, 0.5, 1, 1.5, 2, 2.5, and 3 mg/kg) based on Se NPs supplementation. Chromic oxide, an inert maker, was also added. Fingerlings were fed at a rate of 5% of their body weight. The test meal of 1 mg/kg Se NPs resulted in the highest weight gain (12.31 g) and the lowest feed conversion ratio (1.58). Best hematological indices (RBCs 2.84 106 mm-3, WBCs 7.79 103 mm-3, PLT 66, Hb 8.5 g/100 ml, PCV 25% and MCV 190 fl) and maximum nutrient absorption (crude protein 72%, ether extract 73% and gross energy 67%) were also observed in the case of 1 mg/kg supplementation of Se NPs. Hematology studies indicated that when fish were fed 0.5 mg/kg Se NPs, their levels began to rise. Maximum results were achieved with feed containing 1 mg/kg of Se NPs, but when the concentration increased above 1 mg/kg, the values began to decline. Instead, nutrient digestibility began to increase when the concentration of Se NPs increased to 1 mg/kg and abruptly started to decline with a further increase in Se NPs. The results demonstrated that a sunflower meal-based diet supplemented with Se NPs (1 mg/kg) increased the growth performance, nutritional digestibility, and hematology of C. mrigala fingerlings.

Hybrid adipocyte-derived exosome nano platform for potent chemo-phototherapy in targeted hepatocellular carcinoma.

The high prevalence and severity of hepatocellular carcinoma (HCC) present a significant menace to human health. Despite the significant advancements in nanotechnology-driven antineoplastic agents, there remains a conspicuous gap in the development of targeted chemotherapeutic agents specifically designed for HCC. Consequently, there is an urgent need to explore potent drug delivery systems for effective HCC treatment. Here we have exploited the interplay between HCC and adipocyte to engineer a hybrid adipocyte-derived exosome platform, serving as a versatile vehicle to specifically target HCC and exsert potent antitumor effect. A lipid-like prodrug of docetaxel (DSTG) with a reactive oxygen species (ROS)-cleavable linker, and a lipid-conjugated photosensitizer (PPLA), spontaneously co-assemble into nanoparticles, functioning as the lipid cores of the hybrid exosomes (HEMPs and NEMPs). These nanoparticles are further encapsuled within adipocyte-derived exosome membranes, enhancing their affinity towards HCC cancer cells. As such, cancer cell uptakes of hybrid exosomes are increased up to 5.73-fold compared to lipid core nanoparticles. Our in vitro and in vivo experiments have demonstrated that HEMPs not only enhance the bioactivity of the prodrug and extend its circulation in the bloodstream but also effectively inhibit tumor growth by selectively targeting hepatocellular carcinoma tumor cells. Self-facilitated synergistic drug release subsequently promoting antitumor efficacy, inducing significant inhibition of tumor growth with minimal side effects. Our findings herald a promising direction for the development of targeted HCC therapeutics.

Surface programmed bacteria as photo-controlled NO generator for tumor immunological and gas therapy.

The use of bacteria as living vehicles has attracted increasing attentions in tumor therapy field. The combination of functional materials with bacteria dramatically facilitates the antitumor effect. Here, we presented a rationally designed living system formed by programmed Escherichia Coli MG1655 cells (Ec) and black phosphorus (BP) nanoparticles (NPs). The bacteria were genetically engineered to express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), via an outer membrane YiaT protein (Ec-T). The Ec-T cells were associated with BP NPs on their surface to acquire BP@Ec-T. The designed living system could transfer the photoelectrons produced by BP NPs after laser irradiation and triggered the reductive metabolism of nitrate to nitric oxide for the in situ release at tumor sites, facilitating the therapeutic efficacy and the polarization of tumor associated macrophages to M1 phenotype. Meanwhile, the generation of reactive oxygen species induced the immunogenic cell death to further improve the antitumor efficacy. Additionally, the living system enhanced the immunological effect by promoting the apoptosis of tumor cells, activating the effect of T lymphocytes and releasing the pro-inflammatory cytokines. The integration of BP NPs, MG1655 cells and TRAIL led to an effective tumor therapy. Our work established an approach for the multifunctional antitumor living therapy.

Selenium nanoparticles stimulate osteoblast differentiation via BMP-2/MAPKs/ß-catenin pathway in diabetic osteoporosis.

Aim: To evaluate whether selenium nanoparticles (SeNPs) can stimulate bone formation and inhibit the bone loss involved in hyperglycemia-induced osteoporosis. Methods: Rat osteoblastic UMR-106 cells were used for in vitro studies and female Sprague-Dawley rats were used for type 2 diabetes-associated osteoporosis in vivo study. Results:In vitro studies show that SeNPs promote osteoblast differentiation via modulating alkaline phosphatase (ALP) activity, and promoting calcium nodule formation and collagen content. The authors also provide evidence regarding the involvement of the BMP-2/MAPKs/ß-catenin pathway in preventing diabetic osteoporosis. Further, in vivo and ex vivo studies suggested that SeNPs can preserve mechanical and microstructural properties of bone. Conclusion: To the best of our knowledge, this study provides the first evidence regarding the therapeutic benefits of SeNPs in preventing diabetes-associated bone fragility.

Osteoporosis is a common complication for people with diabetes. High glucose causes oxidative stress, and the antioxidant and anti-inflammatory properties of selenium nanoparticles (SeNPs) make them useful in the treatment of metabolic disorders associated with high glucose levels. The results of this paper report the protective effects of SeNPs in diabetic osteoporosis using rat osteoblastic UMR-106 cells and female Sprague­Dawley rats with type-2 diabetes-induced osteoporosis. SeNPs promote osteoblast differentiation and mineralization in osteoblasts, preserve bone microstructure and improve biomechanical stability, which suggests that SeNPs could be used therapeutically in the maintenance of diabetic osteoporosis.

In vitro evidence of oncofetal antigen and TLR-9 agonist co-delivery by alginate nanovaccines for liver cancer immunotherapy.

Liver cancer is the most common malignant tumor and liver cancer immunotherapy has been one of the research hotspots. To induce antigen-specific antitumor immune responses against liver cancer, we developed antigen and adjuvant co-delivery nanovaccines (APPCs). Polyanionic alginate (ALG) and polycationic polyethyleneimine (PEI) were utilized to co-deliver a glypican-3 peptide antigen and an unmethylated cytosine-phosphate-guanine (CpG) adjuvant by electrostatic interactions. A cellular uptake study confirmed that APPC could promote antigen and adjuvant uptake by dendritic cells (DCs). Importantly, APPC facilitated the endosomal escape of the peptide for antigen delivery into the cytoplasm. In addition, APPC showed significant stimulation of DC maturation in vitro. APPC could also efficiently prime DCs and induce cytotoxic T lymphocyte responses in vivo. The in vitro cell viability assay and the in vivo histocompatibility showed that APPC was non-toxic within the tested concentration. This study demonstrates that the peptide antigen and the CpG adjuvant co-delivery nanovaccine have potential applications in liver cancer immunotherapy.

Carbonic anhydrase IX-targeted H-APBC nanosystem combined with phototherapy facilitates the efficacy of PI3K/mTOR inhibitor and resists HIF-1α-dependent tumor hypoxia adaptation.

BACKGROUND: Non-redundant properties such as hypoxia and acidosis promote tumor metabolic adaptation and limit anti-cancer therapies. The key to the adaptation of tumor cells to hypoxia is the transcriptional and stable expression of hypoxia-inducible factor-1 alpha (HIF-1α). The phosphorylation-activated tumorigenic signal PI3K/AKT/mTOR advances the production of downstream HIF-1α to adapt to tumor hypoxia. Studies have elucidated that acid favors inhibition of mTOR signal. Nonetheless, carbonic anhydrase IX (CAIX), overexpressed on membranes of hypoxia tumor cells with pH-regulatory effects, attenuates intracellular acidity, which is unfavorable for mTOR inhibition. Herein, a drug delivery nanoplatform equipped with dual PI3K/mTOR inhibitor Dactolisib (NVP-BEZ235, BEZ235) and CAIX inhibitor 4-(2-aminoethyl) benzene sulfonamide (ABS) was designed to mitigate hypoxic adaptation and improve breast cancer treatment. RESULTS: ABS and PEG-NH2 were successfully modified on the surface of hollow polydopamine (HPDA), while BEZ235 and Chlorin e6 (Ce6) were effectively loaded with the interior of HPDA to form HPDA-ABS/PEG-BEZ235/Ce6 (H-APBC) nanoparticles. The release of BEZ235 from H-APBC in acid microenvironment could mitigate PI3K/mTOR signal and resist HIF-1α-dependent tumor hypoxia adaptation. More importantly, ABS modified on the surface of H-APBC could augment intracellular acids and enhances the mTOR inhibition. The nanoplatform combined with phototherapy inhibited orthotopic breast cancer growth while reducing spontaneous lung metastasis, angiogenesis, based on altering the microenvironment adapted to hypoxia and extracellular acidosis. CONCLUSION: Taken together, compared with free BEZ235 and ABS, the nanoplatform exhibited remarkable anti-tumor efficiency, reduced hypoxia adaptation, mitigated off-tumor toxicity of BEZ235 and solved the limited bioavailability of BEZ235 caused by weak solubility.

Design of Turmeric Rhizome Extract Nano-Formula for Delivery to Cancer Cells.

Novel turmeric rhizome extract nanoparticles (TE-NPs) were developed from fractions of dried turmeric (Curcuma longa Linn.) rhizome. Phytochemical studies, by using HPLC and TLC, of the fractions obtained from ethanol extraction and solvent-solvent extraction showed that turmeric rhizome ethanol extract (EV) and chloroform fraction (CF) were composed mainly of three curcuminoids and turmeric oil. Hexane fraction (HE) was composed mainly of turmeric oil while ethyl acetate fraction (EA) was composed mainly of three curcuminoids. The optimal TE-NPs formulation with particle size of 159.6 ± 1.7 nm and curcumin content of 357.48 ± 8.39 µM was successfully developed from 47-run D-optimal mixture-process variables experimental design. Three regression models of z-average, d50, and d90 could be developed with a reasonable accuracy of prediction (predicted r2 values were in the range of 0.9120-0.9992). An in vitro cytotoxicity study using MTT assay demonstrated that the optimal TE-NPs remarkably exhibited the higher cytotoxic effect on human hepatoma cells, HepG2, when compared with free curcumin. This study is the first to report nanoparticles prepared from turmeric rhizome extract and their cytotoxic activity to hepatic cancer cells compared with pure curcumin. These nanoparticles might serve as a potential delivery system for cancer therapy.

Solid Lipid Nanoparticles Administering Antioxidant Grape Seed-Derived Polyphenol Compounds: A Potential Application in Aquaculture.

The supply of nutrients, such as antioxidant agents, to fish cells still represents a challenge in aquaculture. In this context, we investigated solid lipid nanoparticles (SLN) composed of a combination of Gelucire® 50/13 and Precirol® ATO5 to administer a grape seed extract (GSE) mixture containing several antioxidant compounds. The combination of the two lipids for the SLN formation resulted in colloids exhibiting mean particle sizes in the range 139-283 nm and zeta potential values in the range +25.6-43.4 mV. Raman spectra and X-ray diffraction evidenced structural differences between the free GSE and GSE-loaded SLN, leading to the conclusion that GSE alters the structure of the lipid nanocarriers. From a biological viewpoint, cell lines from gilthead seabream and European sea bass were exposed to different concentrations of GSE-SLN for 24 h. In general, at appropriate concentrations, GSE-SLN increased the viability of the fish cells. Furthermore, regarding the gene expression in those cells, the expression of antioxidant genes was upregulated, whereas the expression of hsp70 and other genes related to the cytoskeleton was downregulated. Hence, an SLN formulation containing Gelucire® 50/13/Precirol® ATO5 and GSE may represent a compelling platform for improving the viability and antioxidant properties of fish cells.

The Evaluation of Meloxicam Nanocrystals by Oral Administration with Different Particle Sizes.

Meloxicam (MLX) is a non-steroidal anti-inflammatory drug used to treat rheumatoid arthritis and osteoarthritis. However, its poor water solubility limits the dissolution process and influences absorption. In order to solve this problem and improve its bioavailability, we prepared it in nanocrystals with three different particle sizes to improve solubility and compare the differences between various particle sizes. The nanocrystal particle sizes were studied through dynamic light scattering (DLS) and laser scattering (LS). Transmission electron microscopy (TEM) was used to characterize the morphology of nanocrystals. The sizes of meloxicam-nanocrystals-A (MLX-NCs-A), meloxicam-nanocrystals-B (MLX-NCs-B), and meloxicam-nanocrystals-C (MLX-NCs-C) were 3.262 ± 0.016 µm, 460.2 ± 9.5 nm, and 204.9 ± 2.8 nm, respectively. Molecular simulation was used to explore the distribution and interaction energy of MLX molecules and stabilizer molecules in water. The results of differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) proved that the crystalline state did not change in the preparation process. Transport studies of the Caco-2 cell model indicated that the cumulative degree of transport would increase as the particle size decreased. Additionally, plasma concentration-time curves showed that the AUC0-∞ of MLX-NCs-C were 3.58- and 2.92-fold greater than those of MLX-NCs-A and MLX-NCs-B, respectively. These results indicate that preparing MLX in nanocrystals can effectively improve the bioavailability, and the particle size of nanocrystals is an important factor in transmission and absorption.

Anti-oxidant, anti-apoptotic, and mitochondrial regulatory effects of selenium nanoparticles against vancomycin induced nephrotoxicity in experimental rats.

AIM: Nephrotoxicity is the major limiting factor for the clinical use of vancomycin (VCM) for treatment against multi-resistant Gram-positive bacteria. The present research aimed to investigate the ability of selenium nanoparticles (SeNPs) to protect against VCM-induced nephrotoxicity in rats. MAIN METHODS: Experimental rats were divided into five groups; the first was the normal control, the second was treated with VCM (200 mg/kg twice/day, i.p.) for 7 days. The third, fourth, and fifth groups were treated orally with SeNPs (0.5, 1, and 2 mg/kg/day); respectively. SeNPs were administered for 12 days before VCM, 1 week simultaneously with VCM, and for another 1 week after its administration. KEY FINDINGS: Levels of malondialdehyde (MDA), inducible nitric oxide synthase (iNOS), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), and kidney injury molecule-1 (KIM-1) were significantly increased in kidney tissue after VCM administration. Expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), Bcl-2 associated X protein (Bax), caspase 3 and caspase 9 in kidney tissue was significantly increased, while the antioxidant enzymes, mitochondrial complexes, the ATP levels and B-cell lymphoma protein 2 (Bcl-2) were decreased in kidney in the VCM-treated rats compared to the normal control group. Treatment with SeNPs significantly decreased levels of MDA, iNOS, NO, TNF-α, and KIM-1 in the kidney tissue. Administration of SeNPs also downregulated the expression of the proapoptotic agents and enhanced the activities of the antioxidant enzymes and the mitochondrial enzyme complexes in the kidney. SIGNIFICANCE: SeNPs alleviated VCM-induced nephrotoxicity through their anti-oxidant, anti-inflammatory, anti-apoptotic and mitochondrial protective effects.

Lycopene nanoparticles promotes osteoblastogenesis and inhibits adipogenesis of rat bone marrow mesenchymal stem cells.

OBJECTIVE: Lycopene is a carotenoid and antioxidant with potent singlet oxygen quenching ability that reduces oxidative stress and promotes bone health. However, the cellular mechanisms by which lycopene influences bone metabolism are not known. MATERIALS AND METHODS: The present study investigated the effects of lycopene nanoparticles on the differentiation of rat bone marrow-derived mesenchymal stem cells into osteoblasts or adipocytes. RESULTS: In osteogenic medium, lycopene supplementation dose-dependently enhanced osteoblast differentiation, as evidenced by the transcription of Alpl, Runx2, Col1a1, Sp7, and Bglap, higher alkaline phosphatase activity, osteocalcin secretion and extracellular matrix mineralisation seen with Alizarin red S staining, and increased haem oxygenase levels. By contrast, lycopene in adipogenic medium inhibited adipocyte differentiation evidenced by decreases in the transcription of Tnfsf11, Tnfrsf11b, Pparg, Lpl, and Fabp4 and reduced fat accumulation observed by Oil Red O staining. CONCLUSIONS: Lycopene nanoparticles may promote bone health and are considered as a potential candidate for the prevention and/or treatment of bone loss conditions.

Plasmon-Triggered Upconversion Emissions and Hot Carrier Injection for Combinatorial Photothermal and Photodynamic Cancer Therapy.

Despite the unique ability of lanthanide-doped upconversion nanoparticles (UCNPs) to convert near-infrared (NIR) light to high-energy UV-vis radiation, low quantum efficiency has rendered their application unpractical in biomedical fields. Here, we report anatase titania-coated plasmonic gold nanorods decorated with UCNPs (Au NR@aTiO2@UCNPs) for combinational photothermal and photodynamic therapy to treat cancer. Our novel architecture employs the incorporation of an anatase titanium dioxide (aTiO2) photosensitizer as a spacer and exploits the localized surface plasmon resonance (LSPR) properties of the Au core. The LSPR-derived near-field enhancement induces a threefold boost of upconversion emissions, which are re-absorbed by neighboring aTiO2 and Au nanocomponents. Photocatalytic experiments strongly infer that LSPR-induced hot electrons are injected into the conduction band of aTiO2, generating reactive oxygen species. As phototherapeutic agents, our hybrid nanostructures show remarkable in vitro anticancer effect under NIR light [28.0% cancer cell viability against Au NR@aTiO2 (77.3%) and UCNP@aTiO2 (98.8%)] ascribed to the efficient radical formation and LSPR-induced heat generation, with cancer cell death primarily following an apoptotic pathway. In vivo animal studies further confirm the tumor suppression ability of Au NR@aTiO2@UCNPs through combinatorial photothermal and photodynamic effect. Our hybrid nanomaterials emerge as excellent multifunctional phototherapy agents, providing a valuable addition to light-triggered cancer treatments in deep tissue.

The Mechanisms Underlying the Protective Action of Selenium Nanoparticles against Ischemia/Reoxygenation Are Mediated by the Activation of the Ca2+ Signaling System of Astrocytes and Reactive Astrogliosis.

In recent years, much attention has been paid to the study of the therapeutic effect of the microelement selenium, its compounds, especially selenium nanoparticles, with a large number of works devoted to their anticancer effects. Studies proving the neuroprotective properties of selenium nanoparticles in various neurodegenerative diseases began to appear only in the last 5 years. Nevertheless, the mechanisms of the neuroprotective action of selenium nanoparticles under conditions of ischemia and reoxygenation remain unexplored, especially for intracellular Ca2+ signaling and neuroglial interactions. This work is devoted to the study of the cytoprotective mechanisms of selenium nanoparticles in the neuroglial networks of the cerebral cortex under conditions of ischemia/reoxygenation. It was shown for the first time that selenium nanoparticles dose-dependently induce the generation of Ca2+ signals selectively in astrocytes obtained from different parts of the brain. The generation of these Ca2+ signals by astrocytes occurs through the release of Ca2+ ions from the endoplasmic reticulum through the IP3 receptor upon activation of the phosphoinositide signaling pathway. An increase in the concentration of cytosolic Ca2+ in astrocytes leads to the opening of connexin Cx43 hemichannels and the release of ATP and lactate into the extracellular medium, which trigger paracrine activation of the astrocytic network through purinergic receptors. Incubation of cerebral cortex cells with selenium nanoparticles suppresses ischemia-induced increase in cytosolic Ca2+ and necrotic cell death. Activation of A2 reactive astrocytes exclusively after ischemia/reoxygenation, a decrease in the expression level of a number of proapoptotic and proinflammatory genes, an increase in lactate release by astrocytes, and suppression of the hyperexcitation of neuronal networks formed the basis of the cytoprotective effect of selenium nanoparticles in our studies.

Impact of Phytomediated Zinc Oxide Nanoparticles on Growth and Oxidative Stress Response of In Vitro Raised Shoots of Ochradenus arabicus.

Biogenic nanoparticles have potential roles in the growth and development of plants and animals as they are ecofriendly and free of chemical contaminants. In this study, we assessed the effects of phytomediated zinc oxide nanoparticles (ZnONPs) on shoot growth, biochemical markers, and antioxidant system response in Ochradenus arabicus, which is a medicinal plant. The shoot length and fresh and dry weights were found to be higher in groups with 5 and 10 mg/L ZnONPs than in the control. At high concentrations of ZnONPs (50, 100, and 300 mg/L), biomass was decreased in a concentration-dependent manner. The shoot number was observed to be highest at 50 mg/L among all applied concentrations of ZnONPs. The levels of the stress markers proline and TBARS were found to be higher in shoots treated with 100 and 300 mg/L ZnONPs than in the control as well as NP-treated shoots. The levels of antioxidant enzymes were significantly increased at high concentrations of nanoparticles compared with the control. Thus, synthesized phytomediated ZnONPs from shoots of O. arabicus and their application to the same organ of O. arabicus in vitro were found to be effective as a low concentration of nanoparticles promoted shoot growth, resulting in high biomass accumulation. Thus, using green nanotechnology, such endemic plants could be conserved in vitro and multiple shoots could be produced by reducing the phytohormone concentration for multiple uses, such as the production of potential secondary metabolites.

Acidic microenvironment responsive polymeric MOF-based nanoparticles induce immunogenic cell death for combined cancer therapy.

BACKGROUND: The complex tumor microenvironment and non-targeting drugs limit the efficacy of clinical tumor therapy. For ensuring the accurate delivery and maximal effects of anticancer drugs, it is important to develop innovative drug delivery system based on nano-strategies. RESULT: In this study, an intracellular acidity-responsive polymeric metal organic framework nanoparticle (denoted as DIMP) has been constructed, which can co-deliver the chemotherapy agent of doxorubicin (DOX) and phototherapy agent of indocyanine green (ICG) for breast carcinoma theranostics. Specifically, DIMP possesses a suitable and stable nanometer size and can respond to the acidic microenvironment in cells, thus precisely delivering drugs into target tumor sites and igniting the biological reactions towards cell apoptosis. Following in vivo and in vitro results showed that DIMP could be effectively accumulated in tumor sites and induced powerful immunogenic cell death (ICD) effect. CONCLUSION: The designed DIMP displayed its effectiveness in combined photo-chemotherapy with auxiliary of ICD effect under a multimodal imaging monitor. Thus, the present MOF-based strategy may offer a potential paradigm for designing drug-delivery system for image-guided synergistic tumor therapy.

Curcumin for parkinson´s disease: potential therapeutic effects, molecular mechanisms, and nanoformulations to enhance its efficacy.

Parkinson's disease (PD) is one of the most prevalent neurodegenerative disorders worldwide. It is caused by the degeneration of dopaminergic neurons from the substantia nigra pars compacta. This neuronal loss causes the dopamine deficiency that leads to a series of functional changes within the basal ganglia, producing motor control abnormalities. L-DOPA is considered the gold standard for PD treatment, and it may alleviate its clinical manifestations for some time. However, its prolonged administration produces tolerance and several severe side effects, including dyskinesias and gastrointestinal disorders. Thus, there is an urgent need to find effective medications, and current trends have proposed some natural products as emerging options for this purpose. Concerning this, curcumin represents a promising bioactive compound with high therapeutic potential. Diverse studies in cellular and animal models have suggested that curcumin could be employed for the treatment of PD. Therefore, the objective of this narrative mini-review is to present an overview of the possible therapeutic effects of curcumin and the subjacent molecular mechanisms. Moreover, we describe several possible nanocarrier-based approaches to improve the bioavailability of curcumin and enhance its biological activity.

Comparison of Selenium Nanoparticles and Sodium Selenite on the Alleviation of Early Atherosclerosis by Inhibiting Endothelial Dysfunction and Inflammation in Apolipoprotein E-Deficient Mice.

Atherosclerosis and related cardiovascular diseases represent the greatest threats to human health, worldwide. Previous animal studies showed that selenium nanoparticles (SeNPs) and Na2SeO3 might have anti-atherosclerotic activity, but the underlying mechanisms are poorly elucidated. This study compared the anti-atherosclerotic activity of SeNPs stabilized with chitosan (CS-SeNPs) and Na2SeO3 and the related mechanism in a high-fat-diet-fed apolipoprotein E-deficient mouse model of atherosclerosis. The results showed that oral administration of both CS-SeNPs and Na2SeO3 (40 µg Se/kg/day) for 10 weeks significantly reduced atherosclerotic lesions in mouse aortae. Mechanistically, CS-SeNPs and Na2SeO3 not only alleviated vascular endothelial dysfunction, as evidenced by the increase of serum nitric oxide level and the decrease of aortic adhesion molecule expression, but also vascular inflammation, as evidenced by the decrease of macrophage recruitment as well as the expression of proinflammatory molecules. Importantly, these results were replicated within in-vivo experiments on the cultured human endothelial cell line EA.hy926. Overall, CS-SeNPs had a comparable effect with Na2SeO3 but might have more potential in atherosclerosis prevention due to its lower toxicity. Together, these results provide more insights into the mechanisms of selenium against atherosclerosis and further highlight the potential of selenium supplementation as a therapeutic strategy for atherosclerosis.

Ameliorative effect of curcumin and zinc oxide nanoparticles on multiple mechanisms in obese rats with induced type 2 diabetes.

The present study was carried out to investigate the therapeutic effect of synthesized naturally compounds, curcumin nanoparticles (CurNPs) and metal oxide, zinc oxide nanoparticles (ZnONPs) on a high-fat diet (HFD)/streptozotocin (STZ)-induced hepatic and pancreatic pathophysiology in type 2 diabetes mellitus (T2DM) via measuring AKT pathway and MAPK pathway. T2DM rats were intraperitoneally injected with a low dose of 35 mg/kg STZ after being fed by HFD for 8 weeks. Then the rats have orally received treatments for 6 weeks. HFD/STZ-induced hepatic inflammation, reflected by increased phosphorylation of p38-MAPK pathway's molecules, was significantly decreased after nanoparticle supplementation. In addition, both nanoparticles significantly alleviated the decreased phosphorylation of AKT pathway. Further, administration of ZnONPs, CurNPs, conventional curcumin, and ZnSO4 (zinc sulfate), as well as metformin, effectively counteracted diabetes-induced oxidative stress and inflammation in the internal hepatic and pancreatic tissues. Based on the results of the current study, ZnONPs and CurNPs could be explored as a therapeutic adjuvant against complications associated with T2DM. Both nanoparticles could effectively delay the progression of several complications by activating AKT pathway and down-regulating MAPK pathway. Our findings may provide an experimental basis for the application of nanoparticles in the treatment of T2DM with low toxicity.

Antibacterial Activity of Biosynthesized Selenium Nanoparticles Using Extracts of Calendula officinalis against Potentially Clinical Bacterial Strains.

The use of selenium nanoparticles (SeNPs) in the biomedical area has been increasing as an alternative to the growing bacterial resistance to antibiotics. In this research, SeNPs were synthesized by green synthesis using ascorbic acid (AsAc) as a reducing agent and methanolic extract of Calendula officinalis L. flowers as a stabilizer. Characterization of SeNPs was performed by UV-vis spectrophotometry, infrared spectrophotometry (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM) techniques. SeNPs of 40-60 nm and spherical morphologies were obtained. The antibacterial activity of marigold extracts and fractions was evaluated by disk diffusion methodology. The evaluation of SeNPs at different incubation times was performed through the colony-forming unit (CFU) count, in both cases against Serratia marcescens, Enterobacter cloacae, and Alcaligenes faecalis bacteria. Partial antibacterial activity was observed with methanolic extracts of marigold leaves and flowers and total inhibition with SeNPs from 2 h for S. marcescens, 1 h for E. cloacae, and 30 min for A. faecalis. In addition, SeNPs were found to exhibit antioxidant activity. The results indicate that SeNPs present a potentiated effect of both antimicrobial and antioxidant activity compared to the individual use of marigold extracts or sodium selenite (Na2SeO3). Their application emerges as an alternative for the control of clinical pathogens.