scholarly journals Synthesis of Polystyrene-Based Cationic Nanomaterials with Pro-Oxidant Cytotoxic Activity on Etoposide-Resistant Neuroblastoma Cells

Nanomaterials ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 977
Author(s):  
Silvana Alfei ◽  
Barbara Marengo ◽  
Giulia Elda Valenti ◽  
Cinzia Domenicotti

Drug resistance is a multifactorial phenomenon that limits the action of antibiotics and chemotherapeutics. Therefore, it is essential to develop new therapeutic strategies capable of inducing cytotoxic effects circumventing chemoresistance. In this regard, the employment of natural and synthetic cationic peptides and polymers has given satisfactory results both in microbiology, as antibacterial agents, but also in the oncological field, resulting in effective treatment against several tumors, including neuroblastoma (NB). To this end, two polystyrene-based copolymers (P5, P7), containing primary ammonium groups, were herein synthetized and tested on etoposide-sensitive (HTLA-230) and etoposide-resistant (HTLA-ER) NB cells. Both copolymers were water-soluble and showed a positive surface charge due to nitrogen atoms, which resulted in protonation in the whole physiological pH range. Furthermore, P5 and P7 exhibited stability in solution, excellent buffer capacity, and nanosized particles, and they were able to reduce NB cell viability in a concentration-dependent way. Interestingly, a significant increase in reactive oxygen species (ROS) production was observed in both NB cell populations treated with P5 or P7, establishing for both copolymers an unequivocal correlation between cytotoxicity and ROS generation. Therefore, P5 and P7 could be promising template macromolecules for the development of new chemotherapeutic agents able to fight NB chemoresistance.

2014 ◽  
Vol 14 (23) ◽  
pp. 12915-12930 ◽  
Author(s):  
V. Verma ◽  
T. Fang ◽  
H. Guo ◽  
L. King ◽  
J. T. Bates ◽  
...  

Abstract. We assess the potential of the water-soluble fraction of atmospheric fine aerosols in the southeastern United States to generate reactive oxygen species (ROS) and identify major ROS-associated emission sources. ROS-generation potential of particles was quantified by the dithiothreitol (DTT) assay and involved analysis of fine particulate matter (PM) extracted from high-volume quartz filters (23 h integrated samples) collected at various sites in different environmental settings in the southeast, including three urban-Atlanta sites, in addition to a rural site. Paired sampling was conducted with one fixed site in Atlanta (Jefferson Street), representative of the urban environment, with the others rotating among different sites, for ~250 days between June 2012 and September 2013 (N=483). A simple linear regression between the DTT activity and aerosol chemical components revealed strong associations between PM ROS-generation potential and secondary organic aerosol (WSOC – water-soluble organic carbon) in summer, and biomass burning markers in winter. Redox-active metals were also somewhat correlated with the DTT activity, but mostly at urban and roadside sites. Positive matrix factorization (PMF) was applied to apportion the relative contribution of various sources to the ROS-generation potential of water-soluble PM2.5 in urban Atlanta. PMF showed that vehicular emissions contribute uniformly throughout the year (12–25%), while secondary oxidation processes dominated the DTT activity in summer (46%) and biomass burning in winter (47%). Road dust was significant only during drier periods (~12% in summer and fall). Source apportionment by chemical mass balance (CMB) was reasonably consistent with PMF, but with higher contribution from vehicular emissions (32%). Given the spatially large data set of PM sampled over an extended period, the study reconciles the results from previous work that showed only region- or season-specific aerosol components or sources contributing to PM ROS activity, possibly due to smaller sample sizes. The ubiquitous nature of the major sources of PM-associated ROS suggests widespread population exposures to aerosol components that have the ability to catalyze the production of oxidants in vivo.


Drug Research ◽  
2020 ◽  
Vol 70 (06) ◽  
pp. 265-272
Author(s):  
Amir Kiani ◽  
Shadi Heydari Nik ◽  
Adineh Khodadoost ◽  
Ahmad Salimi ◽  
Jalal Pourahmad

AbstractThe link between Ca2+ dysregulation, mitochondria damages, oxidative stress and cellular derangement is particularly evident in neurotoxicity induced by chemotherapeutic agents. In the current study, we investigated effects of trifluoperazine (TFP) as an inhibitor of calmodulin against the cytotoxicity induced by cytarabine (Ara-C) and Ifosfamide (IFOS) on isolated rat neurons and also the mechanisms involved in this toxicity. Isolated rat neurons were pretreated with TFP (100 µM) for 5 min at 37°C, then Ara-C (226 µM) and IFOS (290 µM) were added in separate experiments. After 3 h, the cytotoxicity, reactive oxygen species (ROS), lysosomal membrane destabilization, mitochondrial membrane potential (MMP), lipid peroxidation (LP), glutathione (GSH) and glutathione disulfide (GSSG) levels were measured. Ara-C and IFOS treatments caused a significant decrease in cellular viability, which was accompanied by ROS generation, GSSG/GSH ratio, lipid peroxidation and lysosomal and mitochondrial damages. On the other hand, TFP (100 µM) pre-treatment attenuated Ara-C and IFOS -induced decrease in cell viability. In addition, TFP (100 µM) pre-treatment significantly protected against Ara-C and IFOS -induced increase in ROS generation, lysosomal and mitochondrial damages, lipid peroxidation levels and decrease in GSH/GSSG ratio. Our data provided insights into the mechanism of protection by TFP against Ara-C and IFOS neurotoxicity, which is related, to neuronal ROS formation and mitochondrial damages.


2013 ◽  
Vol 33 (1) ◽  
pp. 41-53 ◽  
Author(s):  
J J van Tonder ◽  
M Gulumian ◽  
A D Cromarty ◽  
V Steenkamp

The organochlorine pesticide, dichlorodiphenyltrichloroethane (DDT), is still used to combat the spread of malaria in several developing countries despite its accumulation and known hepatotoxic effects that have been demonstrated both in vitro and in vivo. N-Acetylcysteine (NAC) is a recognized hepatoprotective agent that has been reported to reduce hepatotoxicity initiated by many different compounds. The aim of this study was to determine whether NAC could counter in vitro hepatocyte injury induced by DDT or its two major metabolites, dichlorodiphenyldichloroethylene and dichlorodiphenyldichloroethane. HepG2 cell cultures were used to assess the following parameters of toxicity: cellular viability, intracellular levels of reactive oxygen species (ROS), mitochondrial membrane potential and initiation of apoptosis. None of the three test compounds induced ROS generation, yet exposure to any of the three compounds produced mitochondrial hyperpolarization, which was countered by NAC pretreatment. All three test compounds also induced apoptotic cell death, which was inhibited by NAC. Despite NAC counteracting some adverse intracellular changes due to organochlorine exposure, it appeared to aggravate the cytotoxic effects of the organochlorine compounds at low test concentrations. As the same outcome may also occur in vivo, results from the present study raise concern about the use of NAC as treatment for DDT-induced hepatotoxicity.


2014 ◽  
Vol 14 (13) ◽  
pp. 19625-19672 ◽  
Author(s):  
V. Verma ◽  
T. Fang ◽  
H. Guo ◽  
L. King ◽  
J. T. Bates ◽  
...  

Abstract. We assess the potential of the water-soluble fraction of atmospheric fine aerosols in the southeastern US to generate reactive oxygen species (ROS) and identify major ROS-associated emission sources. ROS-generation potential of particles was quantified by the dithiothreitol (DTT) assay and involved analysis of fine particulate matter (PM) extracted from high-volume quartz filters (23 h integrated samples) collected at various sites in different environmental settings in the southeast, including three urban Atlanta sites, in addition to a rural site. Paired sampling was conducted with one fixed site in Atlanta (Jefferson Street), representative of the urban environment, with the others rotating among different sites, for ~250 days between June 2012 and September 2013 (N = 483). A simple linear regression between the DTT activity and aerosol chemical components revealed strong associations between PM ROS generation potential and secondary organic aerosol (WSOC) in summer, and biomass burning markers in winter. Redox-active metals were also correlated with the DTT activity, but mostly at urban and roadside sites. Positive matrix factorization (PMF) was applied to apportion the relative contribution of various sources to the ROS generation potential of water-soluble PM2.5 in urban Atlanta. PMF showed that vehicular emissions contribute uniformly throughout the year (12 to 25%), while secondary oxidation processes dominated the DTT activity in summer (46%) and biomass burning in winter (47%). Mineral dust was significant only during drier periods (~12% in summer and fall). Source apportionment by chemical mass balance (CMB) was reasonably consistent with PMF, but with higher contribution from vehicular emissions (32%). Given the spatially large data set of PM sampled over an extended period, the study reconciles the results from previous work that showed only region- or season-specific aerosol components or sources contributing to PM ROS activity, possibly due to smaller sample sizes. Our results indicate that the ability to generate ROS is a generic property of fine PM to which almost all major emission sources contribute to variable extents. The ubiquitous nature of the ROS generation property of ambient particulate matter suggests widespread population exposures to aerosol components that have the ability to catalyze the production of oxidants in vivo.


2020 ◽  
Vol 56 (53) ◽  
pp. 7325-7328 ◽  
Author(s):  
Jingxin Mo ◽  
Meiying Li ◽  
Xianjue Chen ◽  
Qinghua Li

Water-soluble hybrid of C60 on ultrathin graphite enables efficient activation of reactive oxygen species for enhanced phototoxicity to neuroblastoma cells.


2014 ◽  
Vol 173 ◽  
pp. 287-296 ◽  
Author(s):  
Yoko Yamakoshi ◽  
Safwan Aroua ◽  
Thach-Mien Duong Nguyen ◽  
Yuko Iwamoto ◽  
Tsuyoshi Ohnishi

The photoinduced reactive oxygen species (ROS) generation from several water-soluble fullerenes was examined. Macromolecular or small molecular water-soluble fullerene complexes/derivatives were prepared and their 1O2 and O2˙− generation abilities were evaluated by ESR spin-trapping methods. As a result, efficient 1O2 generation was detected from photoexcited C60, not only in organic solvents, but also in aqueous media and especially from small molecule C60–carboxylic acid derivatives. Whereas efficient O2˙− generation was observed in the aqueous solution of the C60/γ-CD complex under photoirradiation.


2019 ◽  
Vol 35 (7) ◽  
pp. 861-876 ◽  
Author(s):  
Proma Bhattacharya ◽  
Sudarsan Neogi

Abstract Nanoparticles have high potential as antibacterial agents, owing to their ability to produce reactive oxygen species (ROS). Recent studies have indicated that this ROS generation is highly affected by the modification of band structure by the introduction of various dopant materials into them. Thus, doped nanoparticles have been extensively studied in the recent literature. The types of dopants, synthesis techniques, and experimental parameters have been found to affect the overall electronic structure of the material, leading to varied antibacterial efficiency. This review summarizes some of the prominent dopant nanomaterials, various methods of synthesizing doped nanoparticles used against bacterial cells, and the main factors involved in it. Despite the extensive research on the mechanism of the antibacterial action, it is still poorly understood mainly due to the inherent complexities and dynamics in cell membranes. Some of the major proposed mechanisms of action of each kind of dopant nanomaterial have also been reported in this work, focusing on the bacterial cell structure.


2018 ◽  
Vol 15 (2) ◽  
pp. 179-207
Author(s):  
Ashaparna Mondal ◽  
Priyankar Paira

Background: Currently ruthenium complexes are immerging as effective anticancer agents due to their less toxicity, better antiproliferative and antimetastatic activity, better stability in cellular environment and most importantly variable oxidation and co-ordination states of ruthenium allows binding this molecule with a variety of ligands. So in past few years researchers have shifted their interest towards organoruthenium complexes having good fluorescent profile that may be applicable for cancer theranostics. Nowadays, photodynamic therapy has become more acceptable because of its easy and effective approach towards killing cancer cells. Objective: Objective of this review article is to shed light on synthesis, characterization, stability and fluorescence studies of various ruthenium [Ru(II) and Ru(III)] complexes and different bioactivity studies conducted with the synthesized compounds to test their candidacy as potent chemotherapeutic agents. Methods: Various heterocyclic ligands containing N,O and S as heteroatom mainly were prepared and subjected to complexation with ruthenium-p-cymene moiety. In most cases [Ru(η6-p-cymene)(µ-Cl)Cl]2 was used as ruthenium precursor and the reactions were conducted in various alcohol medium such as methanol, ethanol or propanol. The synthesized complexes were characterized by 1H NMR and 13C NMR spectroscopy, GC-MS, ESI-MS, elemental analysis and single crystal X-ray crystallography methods. Fluorescence study and stability study were conducted accordingly using water, PBS buffer or DMSO. Stable compounds were considered for cell viability studies. To study the efficacy of the compounds in ROS generation as photosensitizers, in few cases, singlet oxygen quantum yields in presence of light were calculated. Suitable compounds were selected for in vitro & in vivo antiproliferative, anti-invasive activity studies. Result: Many newly synthesized compounds were found to have less IC50 compared to a standard drug cysplatin. Those compounds were also stable preferably in physiological conditions. Good fluorescence profile and ROS generation ability were observed for few compounds. Conclusion: Numerous ruthenium complexes were developed which can be used as cancer theranostic agents. Few molecules were synthesized as photosensitizers which were supposed to generate reactive singlet oxygen species in targeted cellular environment in presence of a particular type of light and thereby ceasing cancer cell growth.


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