Silver nanoparticles induced synaptic degeneration via Ca2+/CaMKII signal and Drp1-dependent mitochondrial disorder in HT22 cells.

Silver nanoparticles (AgNPs) have been widely used in biomedicine and cosmetics, increasing their potential risks in neurotoxicity. But the involved molecular mechanism remains unclear. This study aims to explore molecular events related to AgNPs-induced neuronal damage by RNA-seq, and elucidate the role of Ca2+/CaMKII signal and Drp1-dependent mitochondrial disorder in HT22 cells synaptic degeneration induced by AgNPs. This study found that cell viabilities were decreased by AgNPs in a dose/time-dependent manner. AgNPs also increased protein expression of PINK1, Parkin, synaptophysin, and inhibited PGC-1α, MAP2 and APP protein expression, indicating AgNPs-induced synaptic degeneration involved in disturbance of mitophagy and mitochondrial biogenesis in HT22 cells. Moreover, inhibition of AgNPs-induced Ca2+/CaMKII activation and Drp1/ROS rescued mitophagy disturbance and synaptic degeneration in HT22 cells by reserving aforementioned protein express changes except for PGC-1α and APP protein. Thus, AgNPs-induced synaptic degeneration was mediated by Ca2+/CaMKII signal and Drp1-dependent mitochondrial disorder in HT22 cells, and mitophagy is the sensitive to the mechanism. Our study will provide in-depth molecular mechanism data for neurotoxic evaluation and biomedical application of AgNPs.

Sustained release of Zn from zinc sulfide nanoparticles (ZnS NPs) amplified the bioaccessibility of Zn in soil: Adsorption dynamics and dissolution kinetics.

Controlled-release micronutrient supplementation to provide better bioavailable zinc (Zn) under alkaline soil conditions is a concept of commercial pertinence for sustainable agriculture. High pH stable nano-scaled ZnS is the material under study in the present investigation where the adsorption dynamics and dissolution kinetics of sono-chemically synthesized zinc sulfide nanoparticles (ZnS NPs) were evaluated in comparison to ZnSO4 in Lufa 2.2 soil for supplementation of Zn. The mechanism of adsorption of ZnS NPs and ZnSO4 onto Lufa 2.2 soil was well explained by fitting into the Freundlich adsorption model and pseudo-second order equation. ZnS NPs reflected the stronger ability to get adsorbed on the Lufa 2.2 soil as compared to metal ions, due to higher surface reactivity of NPs and higher Kf value (0.557) than ZnSO4 (0.463). Time relevant enhancement in extractability of Zn from ZnS NPs amended soil and diminution in extractability of Zn from ZnSO4 spiked soil was observed in bioavailability studies. The increased labile pool of Zn from ZnS NPs amended soil over time was due to their slow dissolution in soil and could be adjusted to consider as "sustained released ZnS NPs". Dissolution of ZnS nanoparticles (NPs) in Lufa 2.2 soil adhered to the first-order extraction model, exhibiting extended half-lives of 27.72 days (low dose) and 28.87 days (high dose). This supported prolonged stability, increased reactivity, and reduced ecological risk compared to conventional Zn salt fertilizers, promoting enhanced crop productivity.

The role of DRP1 mediated mitophagy in HT22 cells apoptosis induced by silica nanoparticles.

Silica nanoparticles (SiNPs) are widely used in the biomedical field and can enter the central nervous system through the blood-brain barrier, causing damage to hippocampal neurons. However, the specific mechanism remains unclear. In this experiment, HT22 cells were selected as the experimental model in vitro, and the survival rate of cells under the action of SiNPs was detected by MTT method, reactive oxygen species (ROS), lactate dehydrogenase (LDH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and adenosine triphosphate (ATP) were tested by the kit, the ultrastructure of the cells was observed by transmission electron microscope, membrane potential (MMP), calcium ion (Ca2+) and apoptosis rate were measured by flow cytometry, and the expressions of mitochondrial functional protein, mitochondrial dynein, mitochondrial autophagy protein as well as apoptosis related protein were detected by Western blot. The results showed that cell survival rate, SOD, CAT, GSH-Px, ATP and MMP gradually decreased with the increase of SiNPs concentration, while intracellular ROS, Ca2+, LDH and apoptosis rate increased with the increase of SiNPs concentration. In total cellular proteins,the expressions of mitochondrial functional proteins VDAC and UCP2 gradually increased, the expression of mitochondrial dynamic related protein DRP1 increased while the expressions of OPA1 and Mfn2 decreased. The expressions of mitophagy related proteins PINK1, Parkin and LC3Ⅱ/LC3Ⅰ increased and P62 gradually decreased, as well as the expressions of apoptosis related proteins Apaf-1, Cleaved-Caspase-3, Caspase-3, Caspase-9, Bax and Cyt-C. In mitochondrial proteins, the expressions of mitochondrial dynamic related proteins DRP1 and p-DRP1 were increased, while the expressions of OPA1 and Mfn2 were decreased. Expressions of mitochondrial autophagy associated proteins PINK1, Parkin, LC3II/LC3I increased, P62 decreased gradually, as well as the expressions of apoptosis related proteins Cleaved-Caspase-3, Caspase-3, and Caspase-9 increased, and Cyt-C expressions decreased. To further demonstrate the role of ROS and DRP1 in HT22 cell apoptosis induced by SiNPs, we selected the ROS inhibitor N-Acetylcysteine (NAC) and Dynamin-related protein 1 (DRP1) inhibitor Mdivi-1. The experimental results indicated that the above effects were remarkably improved after the use of inhibitors, further confirming that SiNPs induce the production of ROS in cells, activate DRP1, cause excessive mitochondrial division, induce mitophagy, destroy mitochondrial function and eventually lead to apoptosis.

Antibacterial, antioxidant, and anticancer potential of green fabricated silver nanoparticles made from Viburnum grandiflorum leaf extract.

BACKGROUND: Recently, researchers are focusing on creating new tools to combat the antibiotic resistant bacteria and malignancy issues, which pose significant threats to humanity. Biosynthesized silver nanoparticles (AgNPs) are thought to be a potential solution to these issues. The biosynthesis method, known for its environmentally friendly and cost-effective characteristics, can produce small-sized AgNPs with antimicrobial and anticancer properties. In this study, AgNPs were bio-fabricated from the distilled water and methanolic extracts of Viburnum grandiflorum leaves. Physio-chemical characterization of the bio-fabricated AgNPs was conducted using UV-visible spectroscopy, scanning electron microscopy, energy dispersive X-ray, and X-ray diffraction analysis. RESULTS: AgNPs produced from the methanol extract were smaller in size (12.28 nm) compared to those from the aqueous extract (17.77 nm). The bioengineered AgNPs exhibited a circular shape with a crystalline nature. These biosynthesized AgNPs demonstrated excellent bactericidal activity against both gram-negative (Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. Highest antibacterial activity was observed with the methanol extract against P. aeruginosa (14.66 ± 0.74 mm). AgNPs from the methanol extract also displayed the highest antioxidant activity, with an IC50 value of 188.00 ± 2.67 µg/mL against 2,2-diphenyl-1-picrylhydrazyl (DPPH). Furthermore, AgNPs exhibited notable cytotoxic activity against Rhabdomyosarcoma cell line (RD cell) of human muscle cancer cell. The IC50 values calculated from the MTT assay were 26.28 ± 1.58 and 21.49 ± 1.44 µg/mL for AgNPs synthesized from aqueous and methanol extracts, respectively. CONCLUSION: The methanol extract of V. grandiflorum leaves demonstrates significant potential for synthesizing AgNPs with effective antibacterial, antioxidant, and anticancer actions, making them applicable in various biomedical applications.

Albumin nanoparticles and their folate modified counterparts for delivery of a lupine derivative to hepatocellular carcinoma.

In this study, folate polyethylene glycol CTr albumin nanoparticles (FA-PEG-CTr-NPs) targeting hepatocellular carcinoma (HCC) were prepared. The nanoparticle preparation method was optimized using single-factor and response surface analysis. The prepared nanoparticles were characterized for their particle size, zeta potential, and morphology. The particle size and zeta potential were also determined. Additionally, drug loading, encapsulation efficiency, and in vitro drug release of the nanoparticles were determined. Using the Cell Counting Kit-8 method, their cytotoxicity and their cell-targeted uptake were determined using confocal microscopy and flow cytometry. Finally, the in vivo antitumor impact and tumor-targeting ability of the nanoparticles were evaluated by determining tumor volume inhibition and drug biodistribution and performing hematoxylin-eosin (H&E) staining. It was found that CTr could be effectively encapsulated into albumin nanoparticles and functionalized. The drug loading of the two nanoparticles was 67.12 ± 2.4% and 69.33 ± 2.8%, respectively. Regarding drug release, FA-PEG-CTr-NPs (89.0%) exhibited a superior release rate to CTr-NPs (70.5%) in an acidic environment. The in vitro experiments confirmed that FA-PEG-CTr-NPs yielded better cytotoxicity and faster drug uptake results than CTr and CTr-NPs. In vivo experiments confirmed that FA-PEG-CTr-NPs exhibited markedly better tumor inhibitory activity (inhibition rate was 80.21%), drug safety, and targeting than CTr and CTr-NPs. In conclusion, functionalized nanoparticles (FA-PEG-CTr-NPs) can specifically inhibit the malignant proliferation of HCC cells and are thus a promising nanoagent for the treatment of HCC.

Preparation and Characterization of IL-22 mRNA-loaded Lipid Nanoparticles.

Interleukin-22 (IL-22) has been demonstrated as a critical regulator of epithelial homeostasis and repair; it showed an anti-inflammatory effect against ulcerative colitis. Local microinjection of IL-22 cDNA vector has been shown to be effective in treating ulcerative colitis in mouse models. However, microinjection comes with multiple technical challenges for routine colon-targeted drug delivery. In contrast, oral administration can get around these challenges and provide comparable efficacy. We showed in previous studies that oral administration of new lipid nanoparticles (nLNP)-encapsulated IL-22 mRNA targets the colon region and efficiently ameliorates colitis. This protocol describes the details of preparing and characterizing the nLNP-encapsulated IL-22 mRNA using three major lipids that mimic the natural ginger-derived nanoparticles. It provides an nLNP platform that can be used to orally deliver other types of nucleic acids to the colon.

Bioconjugation studies of an EGF-R targeting ligand on dendronized iron oxide nanoparticles to target head and neck cancer cells.

A major challenge in nanomedicine is designing nanoplatforms (NPFs) to selectively target abnormal cells to ensure early diagnosis and targeted therapy. Among developed NPFs, iron oxide nanoparticles (IONPs) are good MRI contrast agents and can be used for therapy by hyperthermia and as radio-sensitizing agents. Active targeting is a promising method for selective IONPs accumulation in cancer tissues and is generally performed by using targeting ligands (TL). Here, a TL specific for the epidermal growth factor receptor (EGFR) is bound to the surface of dendronized IONPs to produce nanostructures able to specifically recognize EGFR-positive FaDu and 93-Vu head and neck cancer cell lines. Several parameters were optimized to ensure a high coupling yield and to adequately quantify the amount of TL per nanoparticle. Nanostructures with variable amounts of TL on the surface were produced and evaluated for their potential to specifically target and be thereafter internalized by cells. Compared to the bare NPs, the presence of the TL at the surface was shown to be effective to enhance their internalization and to play a role in the total amount of iron present per cell.

Suppression of Autoimmune Rheumatoid Arthritis with Hybrid Nanoparticles That Induce B and T Cell Tolerance to Self-Antigen.

Autoimmune diseases affect over 4% of the world's population. Treatments are generally palliative or use broad spectrum immunosuppressants to reduce symptoms and disease progression. In some diseases, antibodies generated to a single autoantigen are the major cause of pathogenic inflammation, suggesting that treatments to induce tolerance to the autoantigen could be therapeutic. Here we report the development of hybrid nanoparticles (NPs) that induce tolerance in both T cells and B cells. The NPs comprise a lipid monolayer encapsulating a PLGA core loaded with rapamycin that promotes development of regulatory T cells (Tregs). The lipid monolayer displays the protein antigen and a ligand of the B cell inhibitory co-receptor CD22 (CD22L) that act together to suppress activation of B cells recognizing the antigen. We demonstrate that the hybrid NPs decorated with ovalbumin (OVA) elicit tolerance to OVA in naïve mice, as judged by low OVA-specific antibody titers after the challenge. In the K/BxN mouse model of rheumatoid arthritis caused by B and T cell-dependent responses to the self-antigen glucose-6-phosphate-isomerase (GPI), we show that GPI hybrid NPs delay development of disease, with some treated mice remaining arthritis-free for 300 days. We provide evidence that the mechanism of rheumatoid arthritis suppression involves induction of B cell tolerance, as measured by low anti-GPI antibodies and decreased plasma cell populations, and T cell tolerance, as measured by increased Tregs. The results show the potential of this versatile NP platform for inducing immune tolerance to a self-antigen and suppressing autoimmune disease.

Advanced application of stimuli-responsive drug delivery system for inflammatory arthritis treatment.

Inflammatory arthritis is a major cause of disability in the elderly. This condition causes joint pain, loss of function, and deterioration of quality of life, mainly due to osteoarthritis (OA) and rheumatoid arthritis (RA). Currently, available treatment options for inflammatory arthritis include anti-inflammatory medications administered via oral, topical, or intra-articular routes, surgery, and physical rehabilitation. Novel alternative approaches to managing inflammatory arthritis, so far, remain the grand challenge owing to catastrophic financial burden and insignificant therapeutic benefit. In the view of non-targeted systemic cytotoxicity and limited bioavailability of drug therapies, a major concern is to establish stimuli-responsive drug delivery systems using nanomaterials with on-off switching potential for biomedical applications. This review summarizes the advanced applications of triggerable nanomaterials dependent on various internal stimuli (including reduction-oxidation (redox), pH, and enzymes) and external stimuli (including temperature, ultrasound (US), magnetic, photo, voltage, and mechanical friction). The review also explores the progress and challenges with the use of stimuli-responsive nanomaterials to manage inflammatory arthritis based on pathological changes, including cartilage degeneration, synovitis, and subchondral bone destruction. Exposure to appropriate stimuli induced by such histopathological alterations can trigger the release of therapeutic medications, imperative in the joint-targeted treatment of inflammatory arthritis.

Dual-signal amplification electrochemical sensing for the sensitive detection of uranyl ion based on gold nanoparticles and hybridization chain reaction-assisted synthesis of silver nanoclusters.

Herein, a dual-signal amplification electrochemical sensing has been proposed for the ultrasensitive detection of uranyl ions (UO22+) by integration of gold nanoparticles (AuNPs) and hybridization chain reaction (HCR)-assisted synthesis of silver nanoclusters (AgNCs). In this sensing platform, AuNPs are used as an ideal signal amplification carrier, aiming at increasing the loads of UO22+-specific DNAzyme on the gold electrode. In the presence of UO22+, UO22+-specific DNAzyme can be activated, leading to the cleavage of substrate strands (S-DNA). Then, HCR is triggered to produce long dsDNA through hybridization the probe with the ssDNA on the electrode surface. As a result, an amplified electrochemical response can be detected by inserting a large amount of AgNCs generated in situ using dsDNA as template. Featured with amplification efficiency, good specificity and high sensitivity, the strategy could quantitatively detect UO22+ down to 6.2 pM with a linear calibration range from 20 pM to 5000 pM. The proposed sensing platform has been also successfully demonstrated the practical application of detecting UO22+, indicating that the developed method has the potential applications and can open up a new avenue for highly sensitive detection of UO22+ in environmental monitoring.

Amelioration of diethylnitrosamine (DEN) induced renal oxidative stress and inflammation by Carissa carandas embedded silver nanoparticles in rodents.

INTRODUCTION: Inflammation and oxidative stress are the main factors ascribed with interruption in the process of renal tissue impairment. The toxicity of different types of nitrosamine is well recognized in animals and humans. Administration of the smallest quantities of diethylnitrosamine or dimethylnitrosamine either orally or parenterally results into renal damage. Therapeutic effects of phytofabricated silver nanoparticles of Carissa carandas aqueous extract has been scrutinised in current study for the assessment of renal cancer activity in animal model. METHODOLOGY: Phytofabricated silver nanoparticles were characterized by using different instrumentation. Nephroprotective activity of silver nanoparticles at different doses was evaluated against N-diethylnitrosamine (200 mg/kg b.w., intraperitoneal) in animal model. Serum and renal homogenate were taken to evaluate the renal toxicity markers, oxidative stress, and antioxidant parameter, proinflammatory cytokines and histopathological study. RESULT: Significant outcomes of silver nanoparticles in dose dependent manner down regulated the elevated serum marker, tumour marker enzymes and histopathology observation of repaired tissue assured the renal cancer activity in animals. In addition, profile of enzymatic and non-enzymatic antioxidant, proinflammatory cytokines and tumour promotion marker also favours the anticancer property of silver nanoparticles. CONCLUSION: The data of current study reveals silver nanoparticles ameliorates renal oxidative stress and carcinogenesis which was induced by N-diethylnitrosamine and accredited to antioxidant and anticancer activities of phytofabricated nanoparticles by biological approach.

ncRNA therapy with miRNA-22-3p suppresses the growth of triple-negative breast cancer.

Deregulation of noncoding RNAs, including microRNAs (miRs), is implicated in the pathogenesis of many human cancers, including breast cancer. Through extensive analysis of The Cancer Genome Atlas, we found that expression of miR-22-3p is markedly lower in triple-negative breast cancer (TNBC) than in normal breast tissue. The restoration of miR-22-3p expression led to significant inhibition of TNBC cell proliferation, colony formation, migration, and invasion. We demonstrated that miR-22-3p reduces eukaryotic elongation factor 2 kinase (eEF2K) expression by directly binding to the 3' untranslated region of eEF2K mRNA. Inhibition of EF2K expression recapitulated the effects of miR-22-3p on TNBC cell proliferation, motility, invasion, and suppression of phosphatidylinositol 3-kinase/Akt and Src signaling. Systemic administration of miR-22-3p in single-lipid nanoparticles significantly suppressed tumor growth in orthotopic MDA-MB-231 and MDA-MB-436 TNBC models. Evaluation of the tumor response, following miR-22-3p therapy in these models using a novel mathematical model factoring in various in vivo parameters, demonstrated that the therapy is highly effective against TNBC. These findings suggest that miR-22-3p functions as a tumor suppressor by targeting clinically significant oncogenic pathways and that miR-22-3p loss contributes to TNBC growth and progression. The restoration of miR-22-3p expression is a potential novel noncoding RNA-based therapy for TNBC.

Elaboration and characterization of curcumin-loaded soy soluble polysaccharide (SSPS)-based nanocarriers mediated by antimicrobial peptide nisin.

Curcumin was recently attracted great interest owing to its multiple bioactivities; however, the use of curcumin was hindered by its poor solubility and stability. In this study, curcumin-nisin-soy soluble polysaccharide nanoparticles (Cur-Nisin-SSPS-NPs, size = 118.76 nm) have been successfully elaborated to improve the application of curcumin. The formation of Cur-Nisin-SSPS-NPs was mediated by amphiphilic and positively charged nisin: SSPS encapsulated nisin, which was mainly driven by electrostatic attraction. And nisin-SSPS complex encapsulated curcumin mainly through hydrophobic interactions between nisin and curcumin. The encapsulation efficiency of curcumin (91.66%) in this novel nanocarriers was significantly higher than that in nanoparticles prepared by a single SSPS (31.82%) or nisin (41.69%), most likely because more hydrophobic regions of nisin were exposed after interacting with SSPS through electrostatic interaction. Consequently, this facile and green nanocarriers improved the solubility/dispersibility and stability of curcumin and nisin, as well as endowed SSPS-based nanoparticles with antioxidant and antimicrobial activities.

Formulation and Characterization of Solid Lipid Nanoparticles Loading RF22-c, a Potent and Selective 5-LO Inhibitor, in a Monocrotaline-Induced Model of Pulmonary Hypertension.

Pulmonary arterial hypertension (PAH) is a rare but fatal disease characterized by persistent elevated blood pressure in the pulmonary circulation, due to increased resistance to blood flow, through the lungs. Advances in the understanding of the pathobiology of PAH clarify the role of leukotrienes (LTs) that appear to be an exciting new target for disease intervention. Over the years, our group has long investigated this field, detecting the 1,2-benzoquinone RF-22c as the most powerful and selective competitive inhibitor of the enzyme 5-lipoxygenase (5-LO). With the aim to improve the bioavailability of RF-22c and to confirm the role of 5-LO as therapeutic strategy for PAH treatment, we developed a solid lipid nanoparticle (SLN) loaded with drug. Therefore, in monocrotaline (MCT) rat model of PAH, the role of 5-LO has been investigated through the formulation of RF-22c-SLN. The rats were randomly grouped into control group, MCT group, and MCT + RF22-c group. After 21 days, all the animals were sacrificed to perform functional and histological evaluations. RF22-c-SLN treatment was able to significantly reduce the mean pulmonary arterial pressure (mPAP) and precapillary resistance (R-pre) compared to the MCT group. The MCT induced rise in medial wall thickness of pulmonary arterioles, and the cardiomyocytes width were significantly attenuated by RF22-c-SLN formulation upon treatment. The results showed that the selective inhibition of 5-LO improved hemodynamic parameters as well as vascular and cardiac remodeling by preventing induced pulmonary hypertension. The improved sustained release properties and targeting abilities achieved with the innovative nanotechnological approach may be therapeutically beneficial for PAH patients as a consequence of the increase of pharmacological effects and of the possible reduction and/or optimization of the drug frequency of administration.

One-Step Synthesis of Diamine-Functionalized Graphene Quantum Dots from Graphene Oxide and Their Chelating and Antioxidant Activities.

2,2'-(Ethylenedioxy)bis(ethylamine)-functionalized graphene quantum dots (GQDs) were prepared under mild conditions from graphene oxide (GO) via oxidative fragmentation. The as-prepared GQDs have an average diameter of ca. 4 nm, possess good colloidal stability, and emit strong green-yellow light with a photoluminescence (PL) quantum yield of 22% upon excitation at 375 nm. We also demonstrated that the GQDs exhibit high photostability and the PL intensity is poorly affected while tuning the pH from 1 to 8. Finally, GQDs can be used to chelate Fe(II) and Cu(II) cations, scavenge radicals, and reduce Fe(III) into Fe(II). These chelating and reducing properties that associate to the low cytotoxicity of GQDs show that these nanoparticles are of high interest as antioxidants for health applications.

Au@SiO2@RuDS nanocomposite based plasmon-enhanced electrochemiluminescence sensor for the highly sensitive detection of glutathione.

A novel plasmon enhanced electrochemiluminescence (ECL) sensor was fabricated for the highly sensitive detection of glutathione (GSH). First, Au nanoparticles (AuNPs) were coated with silica dioxide to prevent the direct contact of AuNPs and luminophore Ru(bpy)32+; then Ru(bpy)32+-containing silica layer (RuDS) was allowed to grow onto the obtained Au@SiO2. Owing to the high luminescence efficiency of RuDS and the surface plasmon resonance of AuNPs, the nanocomposite Au@SiO2@RuDS exhibited large ECL signal. As free radical scavenger, GSH could react with tri-n-propylamine radical (i.e. TPA+•) and effectively suppress the excitation of Ru(bpy)32+, thus made the ECL signal significantly decrease. By using Nafion as immobilization reagent, the resulting Au@SiO2@RuDS/GCE sensor showed wide linear response ranges (1.0 fM-1.0 nM and 1.0 nM-1.0 µM) and low detection limit (0.5 fM, S/N=3) for GSH. In addition, it had excellent stability, repeatability and reproducibility. The sensor was applied to the detection of GSH in human serum samples and satisfactory results were achieved.

The adjuvant effect of C60(OH)22 nanoparticles promoting both humoral and cellular immune responses to HCV recombinant proteins.

Hepatitis c virus (HCV) infection is one of major causes for chronic liver diseases worldwide and could lead to death. Development of effective HCV vaccines is a powerful auxiliary method of existing treatments. Adjuvants are necessary for modern vaccines to promote immune responses. Among the various nanomaterials that have been developed, multihydroxylated fullerene (C60(OH)22) has been proved as an efficient adjuvant for human immunodeficiency virus DNA vaccine. Here, we utilized three types of HCV recombinant proteins as antigens to investigate the activity of C60(OH)22 as a protein vaccine adjuvant. The proteins were carried by C60(OH)22 in a way of surface adsorption and self-assemble encapsulation. C60(OH)22 at a relatively low dose was sufficient to promote both humoral and cellular immune responses to HCV protein antigens and reduce the usage of antigen. These results demonstrated the positive adjuvant properties of C60(OH)22 when applied to protein vaccines.

Synthesis of Cross-Linked 2-Aminoethyl Methacrylate in P22 Viral Capsid via Atom-Transfer Radical Polymerization.

Virus-like particles (VLPs) resemble viruses, but are devoid their genetic material, rendering them as noninfectious, hollow protein shells. VLPs are ideal templates to synthesize nanoparticles because they have homogeneous size and their empty cavity can provide a confined environment for selectively directed synthesis. Atom-transfer radical polymerization (ATRP) is well suited for directed synthesis of polymers inside VLPs. In addition to being rapid, monomer-promiscuous, and resulting in products with relatively low polydispersity, the simplicity of the ATRP initiator allows it to be readily modified for amending to biomolecules. This chapter describes the polymerization of 2-aminoethyl methacrylate (AEMA) via ATRP in a viral capsid derived from the bacteriophage P22.

Prolonged Effects of Silver Nanoparticles on p53/p21 Pathway-Mediated Proliferation, DNA Damage Response, and Methylation Parameters in HT22 Hippocampal Neuronal Cells.

It is widely accepted that silver nanoparticles (AgNPs) are toxic to biological systems. However, little is known about their actions at molecular level and the cytophysiological effects after AgNP removal. As nanoparticles are suggested a promising tool to transport drugs to the brain for use in neurological conditions, we used HT22 mouse hippocampal neuronal cells as a model to study AgNP-mediated effects after their removal from the cell culture medium. We selected a relatively low concentration of AgNPs, 5 µg/ml, treated the cells for 48 h, and evaluated AgNP-induced cytophysiological effects after 96 h of AgNP removal. AgNP removal did not result in cytotoxicity. In contrast, AgNPs modulated HT22 cell cycle and proliferation and induced oxidative stress and 53BP1 recruitment, which were accompanied by elevated levels of p53 and p21. AgNP-associated diminution in lamin B1 pools did not significantly affect the structure of the nucleus. No disruption in F-actin dynamics was observed upon AgNP treatment. Moreover, we showed for the first time that AgNPs stimulated changes in DNA methylation: the augmentation in 5-methylcytosine (5-mC) and DNMT1, DNMT2, DNMT3a, and DNMT3b levels were observed. The upregulation of DNMT2 may be a part of cellular stress response to AgNP treatment. Taken together, AgNP removal resulted in p53/p21-mediated inhibition of cell proliferation, oxidant-based DNA damage response, and changes in DNA methylation patterns, which suggests that more attention should be paid to the possible outcomes in individuals exposed to nano-sized biomaterials.

A novel [Mn2(µ-(C6H5)2CHCOO)2(bipy)4](bipy)(ClO4)2 complex loaded solid lipid nanoparticles: synthesis, characterization and in vitro cytotoxicity on MCF-7 breast cancer cells.

Manganese (Mn)-based complexes have been drawing attention due to the fact that they are more effective than other metal complexes. However, the use of Mn(II)-based complexes in medicine remains limited because of certain side effects. The aim of this study was to investigate the cytotoxic and apoptotic effects of a novel Mn(II) complex [Mn2(µ-(C6H5)2CHCOO)2(bipy)4](bipy)(ClO4)2 and Mn(II) complex loaded solid lipid nanoparticles (SLNs) on MCF-7 and HUVEC control cells. The average diameter of Mn(II) complex was about 1120 ± 2.43 nm, while the average particle size of Mn(II) complex-SLNs was ∼340 ± 2.27 nm. The cytotoxic effects of Mn(II) complex and Mn(II)-SLNs were 86.8 and 66.4%, respectively (p < .05). Additionally, both Mn(II) complex (39.25%) and Mn(II)-SLNs (38.05%) induced apoptosis and increased the arrest of G0/G1 phase. However, Mn(II) complex exerted toxic effects on the HUVEC control cell (63.4%), whereas no toxic effects was observed when treated with Mn(II)-SLNs at 150 µM. As a consequence, SLNs might be potentially used for metal-based complexes in the treatment of cancer due to reducing size and toxic effects of metal-based complexes.