Comparison of neuroprotective effects of a topiramate-loaded biocomposite based on mesoporous silica nanoparticles with pure topiramate against methylphenidate-induced neurodegeneration.

BACKGROUND: Methylphenidate (MPH) abuse has been criticized for its role in neurodegeneration. Also, a high risk of seizure was reported in the first month of MPH treatment. Topiramate, a broad-spectrum Antiepileptic Drug (AED), has been used as a neuroprotective agent in both aforementioned complications. Nanotechnology is introduced to increase desirable neurological treatment with minimum side effects. We aimed to investigate the potential neuroprotective activity of topiramate loaded on nanoparticles. METHODS AND RESULTS: MTT assay was performed to evaluate the cellular cytotoxicity of Mesoporous Silica Nanoparticles (MSN). Male rats were randomly divided into eight groups. Rats received an intraperitoneal (i.p) MPH (10 mg/kg) injection and a daily oral dose of topiramate (TPM, 30 mg/kg), MSN with Zn core (10 and 30 mg/kg), and MSN with Cu core (10 and 30 mg/kg) for three weeks. On day 21, a seizure was induced by a single injection of pentylenetetrazole (PTZ) to evaluate the protective effects of TPM-loaded nanoparticles on seizure latency and duration following MPH-induced neurotoxicity. Moreover, the hippocampal content of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), malondialdehyde (MDA), and the anti-oxidant enzymes (SOD, GPx, and GR) activities were assessed. Also, BAX and Bcl-2 as two main apoptotic markers were evaluated. RESULTS: MPH neurotoxicity was observed as a raised duration and reduced latency in PTZ-induced seizure. However, TPM-loaded MSN with Zn species (NE) treatment reduced the duration and improved the latency time. Also, NE and, somewhat, TPM-loaded MSN with Cu species (NM) administration reduced inflammatory cytokines, MDA, and Bax levels and increased activities in the rat hippocampus. CONCLUSION: TPM-loaded nanoparticles could be used as neuroprotective agents against MPH-induced neurodegeneration by improving seizure parameters and reducing inflammatory, oxidant, and apoptotic factors.

Exploring mesoporous silica nanoparticles as oral insulin carriers: In-silico and in vivo evaluation.

The advancements in nanoscience have brought attention to the potential of utilizing nanoparticles as carriers for oral insulin administration. This study aims to investigate the effectiveness of synthesized polymeric mesoporous silica nanoparticles (MSN) as carriers for oral insulin and their interactions with insulin and IR through in-silico docking. Diabetic rats were treated with various MSN samples, including pure MSN, Amin-grafted MSN/PEG/Insulin (AMPI), Al-grafted MSN/PEG/Insulin (AlMPI), Zinc-grafted MSN/PEG/Insulin (ZNPI), and Co-grafted MSN/PEG/Insulin (CMPI). The nanocomposites were synthesized using a hybrid organic-inorganic method involving MSNs, graphene oxide, and insulin. Characterization of the nanocomposites was conducted using X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). In vivo tests included the examination of blood glucose levels and histopathological parameters of the liver and pancreas in type 1 diabetic rats. The MSN family demonstrated a significant reduction in blood glucose levels compared to the diabetic control group (p < 0.001). The synthesized nanocomposites exhibited safety, non-toxicity, fast operation, self-repairing pancreas, cost-effectiveness, and high efficiency in the oral insulin delivery system. In the in-silico study, Zn-grafted MSN, Co-grafted MSN, and Al-grafted MSN were selected. Docking results revealed strong interactions between MSN compounds and insulin and IR, characterized by the formation of hydrogen bonds and high binding energy. Notably, Co-grafted MSN showed the highest docking scores of -308.171 kcal/mol and -337.608 kcal/mol to insulin and IR, respectively. These findings demonstrate the potential of polymeric MSN as effective carriers for oral insulin, offering promising prospects for diabetes treatment.

The development of a novel copper-loaded mesoporous silica nanoparticle as a peroxidase mimetic for colorimetric biosensing and its application in H2O2 and GSH assay.

In recent years, the development of nanomaterials-based peroxidase mimics as enzyme sensors has been attracting considerable interest due to their outstanding features, including potent stability, and cost-effectiveness toward natural enzymes. In this work, mesoporous silica nanoparticles functionalized by copper (Cu-MSN) were prepared as a new artificial enzyme for the first time through the sol-gel procedure. A comprehensive investigation of the catalytic activity of Cu-MSN was done through the oxidation of chromogenic peroxidase substrates, 3,3',5,5'-tetramethylbenzidine (TMB), and (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), in the presence of H2O2. The results indicate that the peroxidase-like activity of the as-prepared sample is significantly higher than other nanoparticles. Additionally, for the study, a facile and rapid sensing method based on the enzyme-like activity of Cu-MSN to detect H2O2 and glutathione (GSH) was developed to examine the potency of the proposed biosensor. Preliminary analysis revealed that the limit of detection (LOD) of H2O2 and GSH is 0.2 and 0.0126 µM, in the range of 0.9-100 and 0.042-1 µM, respectively. These findings support the claims for the efficiency of the sensor in detection fields. Also, human serum was utilized as the real sample to obtain additional evidence.

Antibacterial composite: polymeric mesoporous silica nanoparticles and combination of imipenem/meropenem.

Using nanomaterials is a novel strategy to eliminate drug resistance against bacteria. Nanoparticles with metal sites show antimicrobial activities that counteract or obstruct antibiotic-resistant mechanisms expressed by the pathogens. Here, a nanocomposite based on mesoporous silica nanoparticles with active sites of silver, and a combination of imipenem and meropenem as antibiotic drugs, was synthesized and characterized using different physicochemical methods. The antibacterial assessments exhibited sensitivity by Staphylococcus aureus (S. aureus), Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) toward the synthesized composite, which showed a suitable safety profile in human cells. This composite has an excellent synergic mechanism based on reactive oxygen species (ROS) to kill bacteria due to penetrating the microbial membrane. In addition, this composite is resistant to hydrolysis by plasmids and chromosomally mediated ß-lactamases. This nanocomposite showed extraordinary antiseptic power against Gram-positive and Gram-negative microbes.

A novel colorimetric sensor for naked-eye detection of cysteine and Hg2+ based on "on-off" strategy using Co/Zn-grafted mesoporous silica nanoparticles.

In an attempt to explore the significance of inorganic mimetic enzymes as sensors, this study introduces a naked-eye analytical sensing platform for the detection of L-cysteine (cys), mercury ions (Hg2+) based on (turn off/turn-on) catalytic activity of zinc and cobalt grafted mesoporous silica nanoparticles (MSNs). To this end, Zn-MSN and Co/Zn-MSN catalysts were synthesized and characterized using XRD, FT-IR, FESEM, TEM, and nitrogen adsorption-desorption methods. Then, using the intrinsic peroxidase-like activity of as-synthesized samples, the oxidation reactions of the chromogenic substrate (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS)) was designed using H2O2, which produced green colored cation radical of ABTS. Considering the high peroxidase-like activity of Co/Zn-MSN in comparison to Zn-MSN, it was employed to detect cys and then Hg2+. The results indicated that the strong interaction between cys and Co/Zn-MSN was proved by a limit of detection (LOD) down to 0.24 nM and the linear relationship from 0.8-50 nM (turn off). Given the fact that Hg2+ has a high-affinity tendency to combine with cys, we were suggested a novel colorimetric path for sensing of Hg2+ in the presence of cys (turn on). Based on this method, LOD was found 0.17 nM with the linear range of 0.57-50 nM. Taken together, results showed that the as-prepared catalysts are superior to other nanoparticles as a sensor to measure the target molecules in biological monitoring and clinical diagnostics.

Tailoring cysteine detection in colorimetric techniques using Co/Fe-functionalized mesoporous silica nanoparticles.

Over the past decade, there has been a dramatic increase in the number of studies focused on sensors for cysteine (Cys) as a crucial factor in physiological function and disease diagnosis. Among those sensors, nanomaterial-based peroxidase mimetics have received particular attention from researchers. This study introduces a new series of mesoporous silica nanoparticles (MSNs) incorporated with iron and cobalt (Co/Fe-MSN) with a molar ratio of Si/Fe = 10 and cobalt species at 1, 3, and 5 wt% that have great potential in the sensing application. These nanomaterial characterization was investigated by FTIR spectroscopy, SEM, TEM, XRD, and nitrogen adsorption-desorption. The peroxidase activity of these nanomaterials was studied through kinetic analysis. The findings revealed that Co/Fe-MSN (1%) showed higher peroxidatic activity than the others towards the common chromogenic substrate 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) diammonium salt. Based on the enzymatic activity of Co/Fe-MSN (1%), a colorimetric sensing platform was designed to detect H2O2 and Cys. The limit of detection (LOD) for H2O2 and Cys was determined to be 1.1 µM and 0.89 nM, respectively. The results indicated that the proposed enzyme mimic exhibited excellent potential as a sensor in medical diagnostics and biological systems.

Investigation of the emission spectra and cytotoxicity of TiO2 and Ti-MSN/PpIX nanoparticles to induce photodynamic effects using X-ray.

BACKGROUND: Photodynamic therapy (PDT) has been recognized as an effective method for cancer treatment; however, it suffers from limited tissue penetration depth. X-rays are ideal excitation sources for activating self-lighting nanoparticles that can penetrate through deep tumor tissues and convert the X-rays to visible light. In this study, Ti-MSN/PpIX nanoparticles for X-ray induced photodynamic therapy was synthesized. Preparation, characterization, and emission spectrum of Ti-MSN/PpIX nanoparticles as well as PDT activity and toxicity of the nanoparticles on HT-29 cell line were investigated. METHODS: Firstly, mesoporous silica nanoparticles (MSN) were synthesized through sol-gel method. Then, TiO2 and PpIX were loaded in MSN. Next, the emission spectra of TiO2, Ti-MSN, and Ti-MSN/PpIX nanoparticles, while activated by X-ray (6 MVp), were recorded. In addition, viability of cells after treatment by Ti-MSN/PpIX nanoparticles and X-ray irradiation was studied. RESULTS: SEM, TEM and FESEM images of the spherical composite nanoparticles showed that their dimensions were changed by incorporating Ti and organic compound of PpIX. Two-dimensional hexagonal structure with d100-spacing was about 3.5 nm with particle sizes of 70-110 nm. The optical characteristics of TiO2 nanoparticles showed strong emission lines, which effectively overlapped with the absorption wavelengths of protoporphyrin IX (PpIX). Cellular experiments showed Ti-MSN/PpIX nanoparticles have proper biocompatibility, however, after X-ray irradiation, significant decrease of cell viability in the presence of the nanoparticles was observed. CONCLUSION: The presented X-PDT method could enhance RT efficacy and is enable that allows for reducing X-ray dose exposure to healthy tissues to overcome radio-resistant tumors.

Antibacterial Activity of a Novel Biocomposite Chitosan/Graphite Based on Zinc-Grafted Mesoporous Silica Nanoparticles.

INTRODUCTION: A novel biocomposite chitosan/graphite based on zinc-grafted mesoporous silica nanoparticles (CGZM-bio) was synthesized and the antibacterial activities of this compound along with that of Zn-MSN nanoparticles were investigated. METHODS: The CGZM-bio biocomposite was synthesized using sol-gel and post-synthesis method under UV radiation. The characterizations of the samples were carried out using FTIR, XRD, SEM, and nitrogen adsorption and desorption. The antibacterial activity was carried out against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) after 18 h at 310 K. RESULTS: The suspension samples of the Zn-MSN and CGZM-bio (2-100 µg.mL-1) presented antibacterial activities against S. aureus and E. coli. The minimum inhibitory concentration (MIC) values against E. coli for the Zn-MSN and CGZM-bio samples were 10 and 5 µg.mL-1, respectively, while the MIC against S. aureus for both nanomaterials was 10 µg.mL-1. DISCUSSION: The antibacterial activities of these materials are due to the generation of radical oxygen species such as •OH, H2O2, and O2 2- during the UV radiation via the generation of the electron-hole pairs which in turn damage the bacteria cells. These nanomaterials may be used in biomedical devices as antibacterial agents.