Synergistic effect of cold atmospheric pressure plasma and free or liposomal doxorubicin on melanoma cells

Pefani-Antimisiari, Konstantina; Athanasopoulos, D.; Marazioti, Antonia; Sklias, Kyriakos; Rodi, Maria; Lastic, Anne-Lise de; Mouzaki, Αthanasia; Svarnas, P.; Antimisiaris, Sophia G.

doi:10.1038/s41598-021-94130-7

Cited by 34 publications

(33 citation statements)

References 71 publications

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“…This is well fitting with the G2/M cell cycle arrest results as it is well known that when excessive DNA damage occurs, cells undergo apoptosis [35]. Additionally, these findings of CAP induced G2/M cell cycle arrest and apoptosis are well supported by the literature [25,34].…”

Section: Cap Treatment Reduces the Viability And Proliferation Of The...supporting

confidence: 83%

“…Lines, Ma-Mel-19 and UKRV-Mel-15a, in a Dose-Dependent Manner CAP has been previously shown to have potent inhibitory effects on melanoma cells, including the suppression of cell proliferation and the induction of cell death [33,34]. This study expanded on these results by using the human melanoma cell lines, Ma-Mel-19 and UKRV-Mel-15a, and by evaluating their response to direct CAP treatment by the MiniJet-R, an argon and microwave-based plasma jet.…”

Section: Cap Treatment Reduces the Viability And Proliferation Of The...mentioning

confidence: 99%

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Oxidative Stress Differentially Influences the Survival and Metabolism of Cells in the Melanoma Microenvironment

Trzeciak

Zimmer

Gehringer

et al. 2022

Cells

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The cellular composition of the tumor microenvironment, including tumor, immune, stromal, and endothelial cells, significantly influences responses to cancer therapies. In this study, we analyzed the impact of oxidative stress, induced by cold atmospheric plasma (CAP), on tumor cells, T cells, and macrophages, which comprise part of the melanoma microenvironment. To accomplish this, cells were grown in different in vitro cell culture models and were treated with varying amounts of CAP. Subsequent alterations in viability, proliferation, and phenotype were analyzed via flow cytometry and metabolic alterations by Seahorse Cell Mito Stress Tests. It was found that cells generally exhibited reduced viability and proliferation, stemming from CAP induced G2/M cell cycle arrest and subsequent apoptosis, as well as increased mitochondrial stress following CAP treatment. Overall, sensitivity to CAP treatment was found to be cell type dependent with T cells being the most affected. Interestingly, CAP influenced the polarization of M0 macrophages to a “M0/M2-like” phenotype, and M1 macrophages were found to display a heightened sensitivity to CAP induced mitochondrial stress. CAP also inhibited the growth and killed melanoma cells in 2D and 3D in vitro cell culture models in a dose-dependent manner. Improving our understanding of oxidative stress, mechanisms to manipulate it, and its implications for the tumor microenvironment may help in the discovery of new therapeutic targets.

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Section: Cap Treatment Reduces the Viability And Proliferation Of The...supporting

confidence: 83%

Section: Cap Treatment Reduces the Viability And Proliferation Of The...mentioning

confidence: 99%

Oxidative Stress Differentially Influences the Survival and Metabolism of Cells in the Melanoma Microenvironment

Trzeciak

Zimmer

Gehringer

et al. 2022

Cells

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“…Dispersions having a PDI of less than 0.200 or 0.250 are generally considered to have narrow size distribution. Zeta potential was measured in the same dispersions, at 25 • C, utilizing the Doppler electrophoresis technique, as recently reported [28].…”

Section: Vesicle Physicochemical Propertiesmentioning

confidence: 90%

“…The particle size distribution (mean hydrodynamic diameter and polydispersity index) of MOX loaded liposomes dispersed at 0.4 mg/mL lipid, in phosphate-buffered saline (10 mM) with pH 7.40, was measured by dynamic light scattering (DLS) (Malvern Nano-Zs, Malvern Instruments, Malvern, Worcestershire, UK) at 25 • C and a 173 • angle [28]. Each sample was measured 11 times in three independent measurements.…”

Section: Vesicle Physicochemical Propertiesmentioning

confidence: 99%

Moxifloxacin Liposomes: Effect of Liposome Preparation Method on Physicochemical Properties and Antimicrobial Activity against Staphylococcus epidermidis

et al. 2022

Self Cite

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The aim of this study was the development of optimal sustained-release moxifloxacin (MOX)-loaded liposomes as intraocular therapeutics of endophthalmitis. Two methods were compared for the preparation of MOX liposomes; the dehydration–rehydration (DRV) method and the active loading method (AL). Numerous lipid-membrane compositions were studied to determine the potential effect on MOX loading and retention in liposomes. MOX and phospholipid contents were measured by HPLC and a colorimetric assay for phospholipids, respectively. Vesicle size distribution and surface charge were measured by DLS, and morphology was evaluated by cryo-TEM. The AL method conferred liposomes with higher MOX encapsulation compared to the DRV method for all the lipid compositions used. Cryo-TEM showed that both liposome types had round vesicular structure and size around 100−150 nm, while a granular texture was evident in the entrapped aqueous compartments of most AL liposomes, but substantially less in DRV liposomes; X-ray diffraction analysis demonstrated slight crystallinity in AL liposomes, especially the ones with highest MOX encapsulation. AL liposomes retained MOX for significantly longer time periods compared to DRVs. Lipid composition did not affect MOX release from DRV liposomes but significantly altered drug loading/release in AL liposomes. Interestingly, AL liposomes demonstrated substantially higher antimicrobial potential towards S. epidermidis growth and biofilm susceptibility compared to corresponding DRV liposomes, indicating the importance of MOX retention in liposomes on their activity. In conclusion, the liposome preparation method/type determines the rate of MOX release from liposomes and modulates their antimicrobial potential, a finding that deserves further in vitro and in vivo exploitation.

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“…Regarding the in-silico initial conditions, N0=700 cells are considered to match the experimentallymeasured density of ~2510 3 cells per well (considering an average 25±5 μm cell diameter), 10 while cDOX As so, dPlasma=15 s cannot lead to significant modification of the medium's chemistry, and it is not suitable for enhanced B16F10 cell apoptosis and viability decrease. The PC-RPMI impact starts to become noticeable after dPlasma=30 s. Indeed, the corresponding RA-M is 0.93±0.03 and it goes up to 1.26±0.03 at dPlasma=120 s, which is approximately 27 and 73% larger respectively, as compared to the control threshold.…”

mentioning

confidence: 99%

Interrogating an in silico model to determine helium plasma jet and chemotherapy efficacy against B16F10 melanoma cells

Hadjicharalambous

Ioannou

Gazeli

et al. 2022

Applied Physics Letters

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We developed an in-silico approach to model B16F10 melanoma cell response to helium atmospheric pressure plasma jet (APPJ) or/and doxorubicin drug (DOX). The in-silico model is informed by relevant data from previously-published in-vitro experiments (cancer cell viability) providing detailed information on (i) cell population number (Ncell) development during incubation, and (ii) probability values for apoptosis (%PApoptosis) and mitosis (%PMitosis) following cell subjection to plasma-conditioned RPMI-1640 medium (PC-RPMI), DOX, and DOX combined with APPJ. When treating cancer cells with PC-RPMI and DOX separately, at the smallest plasma duration (dPlasma=15 s) and DOX concentration (cDOX=0.05 μM), only a small decline in Nc, increase in %PApoptosis or/and decrease in %PMitosis are measured with respect to the control conditions (non-treated cancer cells). However, cell cytotoxicity is increasingly enhanced with increasing dPlasma and cDOX up to 120 s and 0.5 μM, respectively. At those highest values studied in in-silico, simulated %PApoptosis are significantly larger than %PMitosis resulting in a severe decrease in Ncell compared to control, in agreement with the corresponding in-vitro experiments. Furthermore, cell treatments combining the smallest two cDOX (0.05 and 0.1 μM) with dPlasma=15 s, result in smaller Ncell, larger %PApoptosis and lower %PMitosis compared to PC-RPMI and DOX effects alone. The present in-silico model is particularly useful in plasma (cancer) medicine field since it can effectively simulate and quantify responses of various cancers to APPJ or/and cancer drugs being strongly complementary to in-vitro experiments.

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Synergistic effect of cold atmospheric pressure plasma and free or liposomal doxorubicin on melanoma cells

Cited by 34 publications

References 71 publications

Oxidative Stress Differentially Influences the Survival and Metabolism of Cells in the Melanoma Microenvironment

Oxidative Stress Differentially Influences the Survival and Metabolism of Cells in the Melanoma Microenvironment

Moxifloxacin Liposomes: Effect of Liposome Preparation Method on Physicochemical Properties and Antimicrobial Activity against Staphylococcus epidermidis

Interrogating an in silico model to determine helium plasma jet and chemotherapy efficacy against B16F10 melanoma cells

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