Our Publications Database

Article 58

Enhanced cytotoxicity of irinotecan adsorbed on mesostructured aluminosilicate matrices

Luminita Claudia Miclea, Silviu Nastase, Laura Bajenaru, Raul Augustin Mitran, Cristian Matei, Fawzia Sha’at, Eugen Radu, Mihaela G. Moisescu, Daniela Berger, Tudor Savopol 

Journal: FARMACIA

Year: 2024

DOI: 10.31925/farmacia.2024.5.17

 

3D spheroid culture; microwell array; immunohistochemistry; pathology; glioblastoma; breast adenocarcinoma

Mesostructured silica, such as MCM-41 and SBA-15 and aluminosilicates have demonstrated good biocompatibility and are used as nanosized drug delivery systems (DDSs). Doping with aluminium modulates their physico-chemical properties. This study aimed to assess the metabolic impact of the 24 h or 48 h incubation of NIH3T3 murine fibroblastic cells with three categories of aluminium-doped MCM-41 and SBA-15 used as DDSs for the cytotoxic irinotecan. After 24 h, unloaded Al-doped DDSs at 90 μg/mL presented no toxic effects. Irinotecan release from DDSs followed a Fickian diffusion with various release profiles. Higher Al content led to higher residual drug amounts, while larger pore sizes resulted in faster desorption of irinotecan. Irinotecan loaded onto Al-doped DDSs decreased cell viability compared to irinotecan in solution. The MCM-based carriers demonstrated greater effectiveness in delivering irinotecan than SBA-based DDSs. The 48 h discontinuous exposure to irinotecan-loaded DDSs exhibited similar cytotoxicity to continuous exposure, suggesting a saturation of DDSs cellular uptake. Confocal microscopy revealed that DDSs were embedded in the cell membranes, supporting the hypothesis of an endocytosis-driven uptake. Our results showed that mesoporous aluminosilicates can augment intracellular irinotecan delivery as a Trojan horse.

Article 50

Evaluation of intracellular distribution of folate functionalized silica nanoparticles using fluorescence and hyperspectral enhanced dark field microscopy

Miclea, Luminita Claudia; Mihailescu, Mona; Tarba, Nicolae; Brezoiu, Ana-Maria; Sandu, Ana Maria; Mitran, Raul-Augustin; Berger, Daniela; Matei, Cristian; Moisescu, Mihaela Georgeta; Savopol, Tudor

Journal: Nanoscale

Year: 2022

DOI: 10.1039/d2nr01821g  

 

Folic-Acid, Cell Turnover, Binding-Protein, Cancer, Delivery, Receptor, Expression, Cytotoxicity, Differentiation, Trafficking

Using nanoparticles as carriers for drug delivery systems has become a widely applied strategy in therapeutics and diagnostics. However, the pattern of their intracellular distribution is yet to be clarified. Here we present an in vitro study on the incorporation of mesoporous silica nanoparticles conjugated with folate and loaded with a cytotoxic drug, Irinotecan. The nanoparticles count and distribution within the cell frame were evaluated by means of enhanced dark field microscopy combined with hyperspectral imagery and 3D reconstructions from double-labeled fluorescent samples. An original post-processing procedure was developed to emphasize the nanoparticles’ localization in 3D reconstruction of cellular compartments. By these means, it has been shown that the conjugation of mesoporous silica nanoparticles with folate increases the efficiency of nanoparticles entering the cell and their preferential localization in the close vicinity of the nucleus. As revealed by metabolic viability assays, the nanoparticles functionalized with folate enhance the cytotoxic efficiency of Irinotecan.

Article 46

Influence of surfactant-tailored Mn-doped ZnO nanoparticles on ROS production and DNA damage induced in murine fibroblast cells

Journal: Nature Scientific Reports

Year: 2020

Cell biology, Chemistry, Materials science

     The present study concerns the in vitro oxidative stress responses of non-malignant murine cells exposed to surfactant-tailored ZnO nanoparticles (NPs) with distinct morphologies and different levels of manganese doping. Two series of Mn-doped ZnO NPs were obtained by coprecipitation synthesis method, in the presence of either polyvinylpyrrolidone (PVP) or sodium hexametaphosphate (SHMTP). The samples were investigated by powder X-ray Diffraction, Transmission Electron Microscopy, Fourier-Transform Infrared and Electron Paramagnetic Resonance spectroscopic methods, and N2 adsorption-desorption analysis. The observed surfactant-dependent effects concerned: i) particle size and morphology; ii) Mn-doping level; iii) specific surface area and porosity. The relationship between the surfactant dependent characteristics of the Mn-doped ZnO NPs and their in vitro toxicity was assessed by studying the cell viability, intracellular reactive oxygen species (ROS) generation, and DNA fragmentation in NIH3T3 fibroblast cells. The results indicated a positive correlation between the specific surface area and the magnitude of the induced toxicological effects and suggested that Mn-doping exerted a protective effect on cells by diminishing the pro-oxidative action associated with the increase in the specific BET area. The obtained results support the possibility to modulate the in vitro toxicity of ZnO nanomaterials by surfactant-controlled Mn-doping.

Article 35

Polygonum bistorta L. herba et flores. Polyphenols profile, antioxidant properties and cytotoxic effect on murine fibroblast cell line NIH3T3

Lucia Pîrvu, Fawzia Sha’at, Luminița Claudia Miclea, Tudor Savopol, Georgeta Neagu, Denisa Ioana Udeanu, Mihaela Georgeta Moisescu

Journal: Farmacia

Year: 2017

DOI: 10.1364/BOE.8.002222

Polygonum bistorta, Polyphenols, Antioxidant, Cytotoxicity, Fibroblast cells, NIH3T3

This work aimed to study the polyphenols content, the antioxidant activity and the potential cytotoxic effects on fibroblast
murine cells NIH3T3 of an ethanolic extract (70%, v/v) obtained from the aerial part (herba et flores) of Polygonum bistorta
L. (Polygonaceae family). The tested extract was assessed for its total phenols content: 1.15 mg gallic acid equivalents
(GAE) per 1 mL extract and showed numerous flavonoids compounds such as quercetin, kaempferol and luteolin derivates,
as well as caffeic and chlorogenic phenolic acids. The chemiluminescence (CL) tests indicated a high antioxidant capacity
(IC50 = 0.57 µg GAE/mL), superior to gallic acid (IC50 = 0.85 µg/mL) and rutin (IC50 = 2.54 µg/mL), used as reference
compounds. The cytotoxicity test demonstrated that, at concentrations over 25 µg GAE/mL extract, the ethanolic extracts
from the aerial part of Polygonum bistorta plant species have a significant toxicity on mouse embryonic fibroblast NIH3T3 cells.

Article 31

Correlation of the intracellular reactive oxygen species levels with textural properties of functionalized mesostructured silica

Laura Bajenaru, Daniela Berger, Luminita Miclea, Cristian Matei, Silviu Nastase, Cristian Andronescu, Mihaela G Moisescu, Tudor Savopol

 

Journal: Journal Of Biomedical Materials

Year: 2014

Fibroblasts; Functionalized MCM-41 silica; Intracellular reactive oxygen species; Melanocytes

Mesostructured silica is frequently used in biomedical applications, being considered nontoxic and biocompatible material, suitable for the development of drug delivery systems (DDS). Four functionalized MCM-41 silica materials with hydrophobic (methyl and vinyl) and hydrophilic (3-aminopropyl and 3-mercaptopropyl) groups were obtained by post-synthesis functionalization and characterized by small-angle X-ray diffraction, infrared spectroscopy, thermal analysis, and nitrogen adsorption-desorption isotherms. The main structural and textural parameters of the obtained silica were determined. The effect of the functionalized silica on fibroblast (NIH3T3) and melanocyte cells (B16F10) was studied with respect to the proliferation rate and the levels of reactive oxygen species (ROS). It was found that the textural properties of all samples influenced the levels of intracellular ROS and consequently, the proliferation rate. Both, healthy and malignant cells exhibited linear dependence of ROS levels with the specific surface area values, but with different response. The contribution of the methyl functionalized silica to the ROS level is apart to the general trend.

Article 30

The interaction of aminoglycosides with endothelial cells infected by Pseudomonas Aeruginosa

Savopol, Tudor ; Moraru, Roxana ; Dinn, A ; Kovacs, Eugenia ; Sajin, Gheorghe

Journal: Romanian Journal of Biophysics

Year: 2014

ISBN: 1220-515X

Aminoglycosides, Pseudomonas Aeruginosa, Endothelial Cells

The membrane organization of cultured human endothelial cells (EA.hy926) infected with Pseudomonas aeruginosa (PS) was studied in the temperature range 15–37 oC by using fluorescent depolarization and generalized polarization (GP) measurements on the cells suspensions labeled with TMA-DPH and laurdan, respectively. The opportunistic pathogen Pseudomonas aeruginosa was chosen since this pathogen is the etiologic agent of resistant and recurrent pulmonary infections in cystic fibrosis (CF) patients, who require sustained treatment with antibiotics. The effect of several aminoglycoside antibiotics – gentamicin, amikacin and kanamycin – on membrane organization of infected cultured cells was recorded. The measurements results showed that the presence of aminoglycosides cations induces a rigidity of the infected cell membrane, gentamicin being the most efficient in this respect. This effect is temperature sensitive, being much more pronounced at temperatures close to physiological range. The above information may be of use in determining the treatment regimen of a CF patient who has recurrent infections and requires antibiotics treatment for a longer time.

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