Synthesis and evaluation of modified lens using plasma treatment containing timolol-maleate loaded lauric acid-decorated chitosan-alginate nanoparticles for glaucoma.

Reducing intraocular pressure (IOP) with eye drops is one of the most common ways to control glaucoma. Low bioavailability and high frequency of administration in eye drops are major challenges in ocular pharmacotherapy. Contact lenses have attracted the attention of scientists in recent decades as an alternative method. In this study, with the aim of long-term drug delivery and better patient compatibility, contact lenses with surface modification and nanoparticles were used. In this study, timolol-maleate was loaded into polymeric nanoparticles made of chitosan conjugate with lauric acid and sodium alginate. Then silicon matrix was mixed with a curing agent (10:1), and the suspension of nanoparticles was added to the precursor and cured. Finally, for surface modification, the lenses were irradiated with oxygen plasma at different exposure times (30, 60, and 150 s) and soaked in different BSA concentrations (1, 3, and 5% w/v). The results showed nanoparticles with a size of 50 nm and a spherical shape were synthesized. The best surface modification of the lenses was for 5 (% w/v) albumin concentration and 150 s exposure time, which had the highest increase in hydrophilicity. Drug release from nanoparticles continued for 3 days and this amount increased to 6 days after dispersion in the modified lens matrix. The drug model and kinetic study show the Higuchi model completely supported the release profile. This study represents the novel drug delivery system to control intra-ocular pressure as a candidate platform for glaucoma treatment. Improved compatibility and drug release from the designed contact lenses would prepare new insight into the mentioned disease treatment.

Anti-Leishmanial Effects of a Novel Biocompatible Non-Invasive Nanofibers Containing Royal Jelly and Propolis against Iranian Strain of Leishmania major (MRHO/IR/75/ER): an In-Vitro Study.

Background: Current medications especially the pentavalent antimonial compounds have been used as the first line treatment of cutaneous leishmaniasis (CL), but they have limitations due to serious side effects such as drug resistance, cardio and nephrotoxicity, and high costs. Hence, the demand to find more usable drugs is evident. Synthesis and development of natural, effective, biocompatible, and harmless compounds against Leishmania major is the principal priority of this study. Methods: By electrospinning method, a new type of nanofiber were synthesized from royal jelly and propolis with different ratios. Nanofibers were characterized by Scanning Electron Microscope (SEM), Transmission Electron Microscopy (TEM), Thermogravimetric Analysis (TGA), Contact angle, and Fourier-transform infrared spectroscopy (FTIR). The Half-maximal inhibitory concentration (IC50), Half-maximal effective concentration (EC50) and the 50% cytotoxic concentration (CC50) for different concentrations of nanofibers were determined using quantitative calorimetric methods. Inductively coupled plasma-optical emission spectrometry (ICP-OES) and flow cytometry were performed as complementary tests. Results: The results showed that the proposed formulas provide a new achievement that, despite the significant killing activity on L. major, has negligible cytotoxicity on the host cells. Royal jelly nanofibers have significantly shown the best 72 hours results (IC50= 35 µg/ml and EC50=16.4 µg/ml) and the least cytotoxicity. Conclusion: This study presents a great challenge to introduce a new low-cost treatment method for CL, accelerate wound healing, and reduce scarring with minimal side effects and biocompatible materials. Royal jelly and propolis nanofibers significantly inhibit the growth of L. major in-vitro.

The effect of nanoparticles on pulmonary fibrosis: a systematic review and Meta-analysis of preclinical studies.

Air pollution is a big ecumenical problem associated with public health around the world. The rapid development of nanotechnology worldwide resulted in a significant increase in human exposure with unknown particles, and ultimately leading to an increase in acute and chronic diseases. The effect of nanoparticles on pulmonary fibrosis has been reported in vivo and in vitro studies; however, the results are inconsistent. The present systematic review and meta-analysis of animal preclinical studies was conducted to assess the effect of nanoparticles on pulmonary fibrosis. A systematic search of online databases and gray literature as well as reference lists of retrieved studies was performed up to February 2019 to identify preclinical animal studies. Studies were assessed for methodological quality using the SYstematic Review Center for Laboratory animal Experimentation bias risk tool (SYRCLE's ROB tool). Pooled standardized mean difference (SMD) estimate with corresponding 95% CI was calculated using inverse-variance weights method while random effects meta-analysis was used, taking into account conceptual heterogeneity. To assess the robustness of pooled estimates as well as heterogeneity across studies, sensitivity analysis and Cochran Q statistic (with I2 statistic) was carried out using Stata 11.0. Of 6494 retrieved studies, 85 were reviewed in depth for eligibility. 16 studies met the criteria for inclusion in this systematic review. The meta-analysis was conducted on 10 studies which had reported the mean of TGF-ß in 7 days after exposure by nanoparticles jointly (exposure compared to no exposure). Findings showed that exposure to nanoparticles significantly induced pulmonary fibrosis (SMD: 4.12, 95% CI: 2.57-5.67). A statistical heterogeneity was found [P < 0.001 (Q statistics), I2 = 83.0%] across studies. Nanoparticles were the most influencing in inducing pulmonary fibrosis in animal models. Sensitivity analysis demonstrated consistency of the results, indicating that the meta-analysis model was robust. Publication bias (using visual inspection and statistical tests) was unlikely in the association between nanoparticles and pulmonary fibrosis. We found that the nanoparticles significantly induce pulmonary fibrosis through increasing proinflammatory cytokine TGF-ß and histopathological changes.

Destruction mechanisms of ozone over SARS-CoV-2.

In this pandemic SARS-CoV-2 crisis, any attempt to contain and eliminate the virus will also stop its spread and consequently decrease the risk of severe illness and death. While ozone treatment has been suggested as an effective disinfection process, no precise mechanism of action has been previously reported. This study aimed to further investigate the effect of ozone treatment on SARS-CoV-2. Therefore, virus collected from nasopharyngeal and oropharyngeal swab and sputum samples from symptomatic patients was exposed to ozone for different exposure times. The virus morphology and structure were monitored and analyzed through Atomic Force Microscopy (AFM), Transmission Electron Microscopy (TEM), Atomic Absorption Spectroscopy (AAS), and ATR-FTIR. The obtained results showed that ozone treatment not only unsettles the virus morphology but also alters the virus proteins' structure and conformation through amino acid disturbance and Zn ion release from the virus non-structural proteins. These results could provide a clearer pathway for virus elimination and therapeutics preparation.

Natural polymeric nanoparticles as a non-invasive probe for mesenchymal stem cell labelling.

Non-invasive tracking of stem cells after transplant is necessary for cell therapy and tissue engineering field. Herein, we introduce natural and biodegradable nanoparticle to develop a highly efficient nanoprobe with the ability to penetrate the stem cell for tracking. Based on the use of (Gd3+) to label stem cells for magnetic resonance imaging (MRI) we synthesized nanoparticle-containing Gd3+. Gd3+ could be used as t1-weighted MRI contrast agents. In this study, chitosan-alginate nanoparticles were synthesized as a clinical Dotarem® carrier for decreased t1-weighted. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR) were utilized for nanoprobe characterization and ICP analysis was performed for Gd3+ concentration measurement. The results illustrate that nanoprobes with spherical shape and with a size of 80 nm without any aggregation were obtained. Relaxivity results suggest that r1 in the phantom was 12.8 mM-1s-1 per Gd3+ ion, which is 3.5 times larger than that for Dotarem® (r1 ∼3.6 mM-1s-1 per Gd3+ ion) and this result for synthesized nanoprobe in stem cells 3.56 mM-1s-1 per Gd3+ ion with 2.16 times larger than that for Dotarem® was reported and also enhanced signal in in-vivo imaging was observed. Chitosan-alginate nanoparticles as a novel biocompatible probe for stem cell tracking can be utilized in tissue engineering approach.

New nanoprobe for breast cancer cell imaging based on low-density lipoprotein.

Many malignant cancers have an increased demand for lipoprotein due to the requirement for lipids for the rapid proliferation of the tumours and which is met by the increased availability of LDL through upregulation of LDL transporters. This unique phenomenon is the basis for the use of LDL based nanoparticles for cell imaging. In this study, a novel MR-active LDL nanoparticle was synthesised as the MRI probes. This MR-active LDL was characterised by using different techniques including scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier-transform infra-red spectroscopy (FTIR) and magnetic resonance imaging (MRI). The intracellular uptake of Gd3+ and cytotoxicity was measured by ICP-AES and MTT assay respectively. Results suggest that this nanoprobe with spherical shape and size of 55 nm has reduced relaxation time compared to commercial contrast agent and is introduced as an appropriate imaging probe. The amount of reabsorption of nanoprobe increased up to 6 h and given that the connection of the chelator does not have an effect on reabsorption proves that entry through transporter of APO section has done. This study lays the basis for exploring a personalised medicine strategy by directing a patient's own LDL to cancer cell imaging in the early stages.

Investigating the effect of near infrared photo thermal therapy folic acid conjugated gold nano shell on melanoma cancer cell line A375.

Nowadays, there is growing interest regarding the use of metal Nanoshells as targeted agents of Nano-photo thermal cancer therapy. This study was aimed at synthesis the folic acid (FA)-conjugated with silica @gold core-shell nanoparticles (FA-SiO2@AuNPs) for improving the treatment of melanoma cancer cells. The characterization data showed that the FA-SiO2@AuNPs is spherical in shape and its size is ∼73.7 nm. The intracellular uptake of FA-SiO2@AuNPs into melanoma cells (A375) was measured through the inductively coupled plasma, (∼47.7%). The cytotoxicity of nanoparticles was investigated on A375 and HDF (Human dermal fibroblast) cell lines. Cytotoxicity results indicated that there is no significant cytotoxicity in HDF cell lines treated with nanoparticles. MTT and flow cytometry results showed that the viability of A375 cells treated by SiO2@Au and FA-SiO2@AuNPs was decreased significantly to about 31% and 16% respectively. The higher toxicity of cancer cells was obtained for the cells exposed to 808 nm near-infrared (NIR) laser after incubation with FA-SiO2@AuNPs rather than the non-targeted SiO2@AuNPs. Furthermore, about 64% more cell death was observed for A-375 cells using both photothermal therapy and treatment with FA-SiO2@AuNPs compared to photothermal therapy. Additionally, the majority of the cell deaths were related to the apoptosis process, not necrosis. It can be concluded that FA-SiO2@AuNPs was an effective targeting agent for photothermal therapy in the treatment of melanoma.

NIR triggered glycosylated gold nanoshell as a photothermal agent on melanoma cancer cells.

Nowadays, gold nanoshells are used in targeted nano photothermal cancer therapy. This study surveyed the application of gold nanoshell (GNs) to thermal ablative therapy for melanoma cancer cells and it takes advantage of the near infrared absorption of gold nanoshells. The synthesis and characterization of glycosylated gold nanoshells (GGNs) were done. The cytotoxicity and photothermal effects of GNs on melanoma cells were evaluated using MTT assay and flow cytometry. The characterization data showed that GGNs are spherical, with a hydrodynamic size of 46.7 nm. Results suggest that the cellular uptake of GGNs was about 78%. Viability assays showed no significant toxicity at low concentrations of GNs. The higher heating rate and toxicity of cancer cells were obtained for the cells exposed to 808 nm NIR laser after incubation with GGNs rather than the GNs. The viability of these cells has dramatically decreased by 29%. Furthermore, 61% more cell lethality was achieved for A375 cells using combined photothermal therapy and treatment with GGNs in comparison to NIR radiation alone. In conclusion, our findings suggest that the synthesized gold/silica core-shell nanoparticles conjugated with glucosamine have high potentials to be considered as an efficient metal-nanoshell in the process of targeted cancer photothermal therapy.

Electrically conductive nanomaterials for cardiac tissue engineering.

Patient deaths resulting from cardiovascular diseases are increasing across the globe, posing the greatest risk to patients in developed countries. Myocardial infarction, as a result of inadequate blood flow to the myocardium, results in irreversible loss of cardiomyocytes which can lead to heart failure. A sequela of myocardial infarction is scar formation that can alter the normal myocardial architecture and result in arrhythmias. Over the past decade, a myriad of tissue engineering approaches has been developed to fabricate engineered scaffolds for repairing cardiac tissue. This paper highlights the recent application of electrically conductive nanomaterials (carbon and gold-based nanomaterials, and electroactive polymers) to the development of scaffolds for cardiac tissue engineering. Moreover, this work summarizes the effects of these nanomaterials on cardiac cell behavior such as proliferation and migration, as well as cardiomyogenic differentiation in stem cells.

Gold nanorods reinforced silk fibroin nanocomposite for peripheral nerve tissue engineering applications.

Nowadays, regenerating peripheral nerves injuries (PNIs) remain a major clinical challenge, which has gained a great attention between scientists. Here, we represent a nanocomposite based on silk fibroin reinforced gold nanorods (SF/GNRs) to evaluate the proliferation and attachment of PC12 cells. The morphological characterization of nanocomposites with transmission electron microscopy (TEM) and Scanning electron microscopy (SEM) showed that the fabricated scaffolds have porous structure with interconnected pores that is suitable for cell adhesion and growth. GNRs significantly improved the poor electrical conductivity of bulk silk fibroin scaffold. Evaluating the morphology of PC12 cells on the scaffold also confirmed the normal morphology of cells with good rate of adhesion. SF/GNRs nanocomposites showed better cellular attachment, growth and proliferation without any toxicity compared with bulk SF scaffold. Moreover, immunostaining studies represented the overexpression of neural specific proteins like nestin and neuron specific enolase (NSE) in the cells cultured on SF/GNRs nanocomposites in comparison to neat SF scaffolds.

Bioactive Salen-type Schiff Base Transition Metal Complexes as Possible Anticancer Agents.

Although metal-based anticancer drugs have been recognized as the most effective agents over the organic compounds, non-selectivity and high toxic effects have limited their applications in a way that only three Pt-analogues have progressed into clinical use. These problems have spurred chemists to develop different strategies based on alternative targets. This work focuses on predicting potency and mode of interactions of a series of salen type Schiff base transition metal complexes derived from meso-1,2-diphenyl-1,2-ethylenediamine, over some proteins (HDAC7, HDAC2, CatB, B-RAF kinase, TopII, RNR, TS, and rHA) using computational docking method, to be later considered as possible anticancer agents. The obtained results showed that all complexes exhibited higher affinity for HDAC7 than the other targets. Moreover, the bromo-derivatives of the copper compounds were more active on HDAC7 than the other derivatives. Such bromo compounds showed considerable interactions with Kinase, RNR, TS, and CatB. Contrary to Histone deacetylase (HAD)C7; HDAC2 was predicted to be relatively poor target. As expected, formation of the hydrophobic interactions between the metal complexes and the protein targets were essential for activity of the metal compounds. This study provides some more information for further optimizations and development of new metallodrugs as enzyme inhibitors for potential therapeutic agents.

Comparison of the effects of MnO2-NPs and MnO2-MPs on mitochondrial complexes in different organs.

Today, nanoparticles (NPs) have been widely used in various fields. Manganese oxide nanoparticles have attracted a lot of attention due to many applications. One of the major concerns regarding the widespread use of various NPs is the exposure and accumulation in human organs and finally toxicity. The generation of reactive oxygen species (ROS) by mitochondria is one of the most important mechanisms of toxicity suggested by published studies induced by other NPs. However, limited studies have been conducted on the mechanism of toxicity of MnO2-NPs and MnO2-microparticles (MnO2-MPs). In this study, we compared the accumulation of MnO2-NPs and MnO2-MPs in different tissues and evaluated their effects on mitochondrial complexes in isolated mitochondria. Our results showed that intravascular (iv) administration of the MnO2-NPs in the same dose compared to the MnO2-MPs resulted in more accumulation in the C57 mouse female tissues. The effect of MnO2-NPs and MnO2-MPs in mitochondria showed that complexes I and III play an important role in increasing ROS generation and this effect is related to type of tissue. Also, our results showed that exposure to MnO2-NPs and MnO2-MPs reduced the activity of mitochondrial complexes II and IV. Our results suggest that the toxicity of the MnO2-NPs is higher than that of the MnO2-MPs and can lead to the depletion of antioxidant status, likely induction of apoptosis, cancer, and neurodegenerative disease. Abbreviations: NPs: nanoparticles; ROS: reactive oxygen species; SDH: succinate dehydrogenase; DCFH-DA: dichloro-dihydro-fluorescein diacetate; ELISA: enzyme-linked immunosorbent assay; MnO2-NPs: manganese oxide nanoparticles.

Chitosan-alginate nano-carrier for transdermal delivery of pirfenidone in idiopathic pulmonary fibrosis.

Pirfenidone (PFD) is one of the pyridine family components with anti-inflammatory, antifibrotic effects and US FDA approved for the treatment of idiopathic pulmonary fibrosis (IPF). Presently, PFD is administered orally and this has setbacks. Hence, it is important to eliminate the pharmacotherapeutic limitations of PFD. This research was carried out to study the possibility of transdermal delivery of PFD using chitosan-sodium alginate nanogel carriers. In order to synthesize chitosan-sodium alginate nanoparticles loaded with PFD, the pre-gelation method was used. Scanning electron microscopy (SEM), transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier-transform infrared spectroscopy (FTIR) analyses were used for the characterization. Drug encapsulation and release manner were studied using UV spectroscopy. Ex vivo permeation examinations were performed using Franz diffusion cell and fluorescence microscopy. The results showed that nanoparticles having spherical morphology and size in the range of 80 nm were obtained. In vitro drug release profile represents sustained release during 24 h, while 50% and 94% are the loading capacity and efficiency, respectively. Also, the skin penetration of PFD loaded in nanoparticles was significantly increased as compared to PFD solution. The obtained results showed that synthesized nanoparticles can be considered as promising carriers for PFD delivery.

Structure-based pharmacophore design and virtual screening for novel potential inhibitors of epidermal growth factor receptor as an approach to breast cancer chemotherapy.

Cancer cells are described with features of uncontrolled growth, invasion and metastasis. The epidermal growth factor receptor subfamily of tyrosine kinases (EGFR-TK) plays a crucial regulatory role in the control of cellular proliferation and progression of various cancers. Therefore, its inhibition might lead to the discovery of a new generation of anticancer drugs. In the present study, structure-based pharmacophore modeling, molecular docking and molecular dynamics simulations were applied to identify potential hits, which exhibited good inhibition on the proliferation of MCF-7 breast cancer cell line and favorable binding interactions on EGFR-TK. Selected compounds were examined for their anticancer activity against the Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line which overexpresses EGFR using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay. Compounds 1 and 2, with an isoindoline-1-one core, induced significant inhibition of breast cancer cells proliferation with IC[Formula: see text] values 327 and 370 nM, respectively.

Nanogel-based natural polymers as smart carriers for the controlled delivery of Timolol Maleate through the cornea for glaucoma.

Despite frequent scientific efforts, efficient ocular drug delivery is a major challenge for pharmaceutical scientists. Poor bioavailability of ophthalmic solutions can be overcome by using smart ophthalmic drug-delivery systems. In this research, loading and delivery of Timolol Maleate (TM) through the cornea by synthesized nanoparticles based on biopolymers (chitosan-alginate) were studied. The physico-chemical properties of these nanoparticles were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and dynamic light scattering (DLS). Loading and release were evaluated by a UV-vis spectrometer and the ex vivo permeation study was carried out using the Franz Diffusion Cell and fluorescent microscopy studies. The results indicated that morphology and size of nanoparticles were spherical and in the range of 80-100nm. The loading capacity and encapsulation efficiency were about 42% and 94% respectively. They illustrated a burst release in the first hour followed by a slower and more sustained drug release during the next 24h. Also, the results indicated that the cornea penetration of TM loaded in nanoparticles was twice than that of TM. Hence, this nanocarrier can be considered as a suitable candidate for controlled TM delivery and release through the cornea.

Acute Toxicity Evaluation of Glycosylated Gd3+-Based Silica Nanoprobe.

PURPOSE: Early stage diseases diagnosed using magnetic resonance imaging (MRI) techniques is of high global interest as a potent noninvasive modality. MRI contrast agents are improved through modifications in structural and physicochemical properties of the applied nanoprobes. But, the potential toxic effects of nanoprobes upon exposure to biological systems are still a major concern. PROCEDURE: In this study, the acute toxicity of glycosylated Gd3+-based silica mesoporous nanospheres (GSNs) as a MRI contrast agent was evaluated in Balb/c mice. In order to evaluate in vivo toxicity of GSN, preclinical studies, daily weight monitoring, hematological/blood chemistry tests, and histological assessment were conducted. Magnetic resonance relaxivities of GSN was determined using a MRI scanner. RESULTS: The obtained results suggest that in vivo toxicity of GSN was mostly influenced by nanoparticle surface area, functionality, and nanoparticle zeta potential. The maximum tolerated dose (MTD) increased in the following order: mesoporous silica nanospheres (MSNs) at 1 mg/mice < GSN (aspect ratio 1, 2, 8) at 40 mg/mice. The results also indicate GSN, one of the best cell imaging contrast agent, which does not show any significant toxicity on multiple vital organs following injection of 20 mg/mice, while a significant T1-weighted enhancement was observed in whole body of a Balb/c mice 15 min postinjection of (5 µmol/kg) of body weight of GSN. CONCLUSIONS: These results shed light on the functionality of MSNs to minimize in vivo toxicity. Also, glyconanoprobe can be beneficially used for nanomedicine and cellular imaging applications without any significant toxicity.

In Vitro Evaluation of Gd(3+)-Anionic Linear Globular Dendrimer-Monoclonal Antibody: Potential Magnetic Resonance Imaging Contrast Agents for Prostate Cancer Cell Imaging.

PURPOSE: Early stage prostate cancer diagnosis is of high global interest. Magnetic resonance imaging (MRI) is a non-invasive modality for early cancer diagnosis, in particular for prostate cancer detection. The research aim is to synthesize a nanodendrimer and its conjugate with C595 monoclonal antibody (mAb C595), against prostate cancer, followed by its chelating with Gd(3+). PROCEDURES: Anti-MUC-1 mAb C595 was conjugated to an anionic linear globular dendrimer (ALGDG2). The polyethylene glycol core and citric acid shell were synthesized followed by loading with Gd(3+) to make novel contrast agents for functional MRI. The in vitro behavior and MRI parameters of the nanoconjugate were investigated performing several studies such as cell toxicity and TNF-alpha evaluations. The investigation of magnetic resonance imaging parameters indicated how well nanoconjugate performs in (1)H-NMR and (17)O-NMR in vitro. RESULTS: Results showed a potential specific MRI activity by improving the swelling responses cell binding. The MTT (2-(4,5-dimethyl-2-thiazolyl)-3,5-diphenyl-2H-tetrazolium bromide) assay demonstrated that this contrast agent had significant cytotoxicity on prostate cancer cells. CONCLUSIONS: These results showed that Gd(3+)-ALGDG2-C595 is a potential prostate molecular imaging agent and could be considered as an ideal functional nanoprobe. Additionally, further investigations by clinical trials are in the pipeline.

Piperazine and its carboxylic acid derivatives-functionalized mesoporous silica as nanocarriers for gemcitabine: adsorption and release study.

Piperazine-functionalized SBA-15 nanorods were synthesized by post grafting method with methyldimethoxysilylpropylpiperazine (MDSP). The carboxylic acid derivatives of piperazine-functionalized SBA-15 nanorods were obtained using two different kinds of precursors (bromoacetic acid and succinic anhydride). The prepared materials were used as nanocarriers for the anticancer drug (gemcitabine). The obtained samples were characterized by SAXS, N2 adsorption-desorption, SEM, TEM, DLS, thermogravimetric analysis, FTIR, Raman and UV spectroscopies. The adsorption and release properties of all samples were investigated. In vitro study included cell toxicity. It was found that the surface functionalization increases the interaction between the carrier and gemcitabine and results in the loading enhancement of the drug. In addition, the adsorption of gemcitabine on the modified mesoporous matrix depends on the type of the introduced functional groups. The carboxylic acid-modified samples have higher loading content, due to the strong interaction with gemcitabine. The maximum content of deposited drug in the modified SBA-15 nanorods is close to 36wt.% that it is related to PC2-SBA-15 sample which obtained using succinic anhydride. The obtained results reveal that the surface functionalization leads toward a significant decrease of the drug release rate without any appreciable cytotoxicity. No significant differences are observed among the drug release rate from the modified samples.

Breast cancer cells imaging by targeting methionine transporters with gadolinium-based nanoprobe.

PURPOSE: Early cancer diagnosis using MRI imaging is of high global interest as a non-invasive and powerful modality. In this study, methionine was conjugated on gadolinium-based mesoporous silica nanospheres to evaluate intra-cellular uptake and its accumulation in human breast cancer cells. PROCEDURES: The contrast agent was synthesized and characterized using different techniques including N2 physisorption, thermal gravimetric analysis, dynamic light scattering, and inductively coupled plasma atomic emission spectroscopy (ICP-AES). The intra-cellular uptake of Gd(3+) was measured by ICP-AES, fluorescent microscopy, and flow cytometry. Finally, cellular and tumor MR imaging were performed to determine in vitro and in vivo relaxometry. RESULTS: According to the results, the contrast agents accumulated in tumor cells both in vitro and in vivo. There was no significant cellular toxicity on either normal or cancer cells along with strong intense signal on T 1 compared to the unlabeled cells. CONCLUSIONS: The results showed that the novel contrast agent could become a useful tool in early detection of cancer.

Conjugation of glucosamine with Gd3+-based nanoporous silica using a heterobifunctional ANB-NOS crosslinker for imaging of cancer cells.

BACKGROUND: The aim of this study was to synthesize Gd(3+)-based silica nanoparticles that conjugate easily with glucosamine and to investigate their use as a nanoprobe for detection of human fibrosarcoma cells. METHODS: Based on the structure of the 2-fluoro-2-deoxy-D-glucose molecule ((18)FDG), a new compound consisting of D-glucose (1.1 nm) was conjugated with a Gd(3+)-based mesoporous silica nanoparticle using an N-5-azido-2-nitrobenzoyloxy succinimide (ANB-NOS) crosslinker The contrast agent obtained was characterized using a variety of methods, including Fourier transform infrared spectroscopy, nitrogen physisorption, thermogravimetric analysis, scanning and transmission electron microscopy, and inductively coupled plasma atomic emission spectrometry (ICP-AES). In vitro studies included cell toxicity, apoptosis, tumor necrosis factor-alpha, and hexokinase assays, and in vivo tests consisted of evaluation of blood glucose levels using the contrast compound and tumor imaging. The cellular uptake study was validated using ICP-AES. Magnetic resonance relaxivity of the contrast agent was determined using a 1.5 Tesla scanner. RESULTS: ANB-NOS was found to be the preferred linker for attaching glucosamine onto the surface of the mesoporous silica nanospheres. The r1 relaxivity for the nanoparticles was 17.70 mM(-1)s(-1) per Gd(3+) ion, which is 4.4 times larger than that for Magnevist® (r1 approximately 4 mM(-1)s(-1) per Gd(3+) ion). The compound showed suitable cellular uptake (75.6% ± 2.01%) without any appreciable cytotoxicity. CONCLUSION: Our results suggest that covalently attaching glucosamine molecules to mesoporous silica nanoparticles enables effective targeted delivery of a contrast agent.