Thermosensitive hydrogels to deliver reactive species generated by cold atmospheric plasma: a case study with methylcellulose

Solé‐Martí, Xavi; Vilella, Tània; Labay, Cédric; Tampieri, Francesco; Ginebra, Maria‐Pau; Canal, Cristina

doi:10.1039/d2bm00308b

Cited by 14 publications

(24 citation statements)

References 50 publications

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“…However, in the majority of in vitro studies investigating CAP effects, carbohydrates are involved as the primary energy source of cell culture media (5–10 mM) or as gelling agents (% range). 6 , 26 The potential oxidation products may contribute to the observed effects and the subsequent conclusions.…”

Section: Introductionmentioning

confidence: 99%

“…Li et al reported that treating 20 mM of aqueous (D 2 O/PBS) sugar solutions ( d -ribose, d -glucose, and d -sucrose) with air dielectric-barrier discharge plasma (1 mm distance of contact surface) led to a full decomposition into low-molecular-weight organic acids, for example, oxalic, glycolic, tartaric, glyceric, and formic acid. However, in the majority of in vitro studies investigating CAP effects, carbohydrates are involved as the primary energy source of cell culture media (5–10 mM) or as gelling agents (% range). , The potential oxidation products may contribute to the observed effects and the subsequent conclusions.…”

Section: Introductionmentioning

confidence: 99%

“…However, in the majority of in vitro studies investigating CAP effects, carbohydrates are involved as the primary energy source of cell culture media (5−10 mM) or as gelling agents (% range). 6,26 The potential oxidation products may contribute to the observed effects and the subsequent conclusions. Besides fundamental considerations in CAP-related biomedical research, the oxidation of carbohydrates by CAP as a scalable and cost-efficient method may offer new opportunities in chemical processing.…”

Section: ■ Introductionmentioning

confidence: 99%

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d-Glucose Oxidation by Cold Atmospheric Plasma-Induced Reactive Species

et al. 2022

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The glucose oxidation cascade is fascinating; although oxidation products have high economic value, they can manipulate the biological activity through posttranslational modification such as glycosylation of proteins, lipids, and nucleic acids. The concept of this work is based on the ability of reactive species induced by cold atmospheric plasma (CAP) in aqueous liquids and the corresponding gas–liquid interface to oxidize biomolecules under ambient conditions. Here, we report the oxidation of glucose by an argon-based dielectric barrier discharge plasma jet (kINPen) with a special emphasis on examining the reaction pathway to pinpoint the most prominent reactive species engaged in the observed oxidative transformation. Employing d -glucose and d -glucose- 13 C 6 solutions and high-resolution mass spectrometry and ESI-tandem MS/MS spectrometry techniques, the occurrence of glucose oxidation products, for example, aldonic acids and aldaric acids, glucono- and glucaro-lactones, as well as less abundant sugar acids including ribonic acid, arabinuronic acid, oxoadipic acid, 3-deoxy-ribose, glutaconic acid, and glucic acid were surveyed. The findings provide deep insights into CAP chemistry, reflecting a switch of reactive species generation with the feed gas modulation (Ar or Ar/O 2 with N 2 curtain gas). Depending on the gas phase composition, a combination of oxygen-derived short-lived hydroxyl ( • OH)/atomic oxygen [O( 3 P)] radicals was found responsible for the glucose oxidation cascade. The results further illustrate that the presence of carbohydrates in cell culture media, gel formulations (agar), or other liquid targets (juices) modulate the availability of CAP-generated species in vitro . In addition, a glycocalyx is attached to many mammalian proteins, which is essential for the respective physiologic role. It might be questioned if its oxidation plays a role in CAP activity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: ■ Introductionmentioning

confidence: 99%

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d-Glucose Oxidation by Cold Atmospheric Plasma-Induced Reactive Species

et al. 2022

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“…For these reasons, interaction of each individual polymer with CAP should be carefully assessed. To this end, different polymers have been considered to date, including alginate, [ 35 ] gelatin [ 149 ] and their combination, methylcellulose, [ 150 ] polyethyleneoxyde‐based copolymers, [ 161 ] and polyethyleneglycol–polylactide copolymers. [ 162 ] In all cases, RONS were successfully generated within the polymer solutions in a CAP treatment time dependent manner, and the polymers maintained the ability to crosslink and form self‐standing hydrogels (through different crosslinking methods including ionic crosslinking, thermal gelling, or UV crosslinking).…”

Section: Cap Treatment Modalities In Clinicsmentioning

confidence: 99%

“…[ 149 ] In contrast, in CAP‐treated methylcellulose solutions, H 2 O 2 and NO 3 − showed a certain decrease while NO 2 − remained essentially unaltered. [ 150 ] Beside, the crosslinking process could also influence the concentration of RONS initially generated by the CAP treatment. It was reported that for methylcellulose PTH that was gelled thermally, NO 2 − and NO 3 − remained essentially unchanged, but the concentration of H 2 O 2 strongly decreased.…”

Section: Cap Treatment Modalities In Clinicsmentioning

confidence: 99%

Current State of Cold Atmospheric Plasma and Cancer‐Immunity Cycle: Therapeutic Relevance and Overcoming Clinical Limitations Using Hydrogels

et al. 2023

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Cold atmospheric plasma (CAP) is a partially ionized gas that gains attention as a well-tolerated cancer treatment that can enhance anti-tumor immune responses, which are important for durable therapeutic effects. This review offers a comprehensive and critical summary on the current understanding of mechanisms in which CAP can assist anti-tumor immunity: induction of immunogenic cell death, oxidative post-translational modifications of the tumor and its microenvironment, epigenetic regulation of aberrant gene expression, and enhancement of immune cell functions. This should provide a rationale for the effective and meaningful clinical implementation of CAP. As discussed here, despite its potential, CAP faces different clinical limitations associated with the current CAP treatment modalities: direct exposure of cancerous cells to plasma, and indirect treatment through injection of plasma-treated liquids in the tumor. To this end, a novel modality is proposed: plasma-treated hydrogels (PTHs) that can not only help overcome some of the clinical limitations but also offer a convenient platform for combining CAP with existing drugs to improve therapeutic responses and contribute to the clinical translation of CAP. Finally, by integrating expertise in biomaterials and plasma medicine, practical considerations and prospective for the development of PTHs are offered. BackgroundCold atmospheric plasma (CAP) is a partially ionized gas that represents a promising tool in biomedical research, with medically

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Injectable Plasma‐Treated Alginate Hydrogel for Oxidative Stress Delivery to Induce Immunogenic Cell Death in Osteosarcoma

Živanić,

Espona‐Noguera,

Verswyvel

et al. 2023

Adv Funct Materials

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Cold atmospheric plasma (CAP) is a source of cell‐damaging oxidant molecules that may be used as low‐cost cancer treatment with minimal side effects. Liquids treated with cold plasma and enriched with oxidants are a modality for non‐invasive treatment of internal tumors with cold plasma via injection. However, liquids are easily diluted with body fluids which impedes high and localized delivery of oxidants to the target. As an alternative, plasma‐treated hydrogels (PTH) emerge as vehicles for the precise delivery of oxidants. This study reports an optimal protocol for the preparation of injectable alginate PTH that ensures the preservation of plasma‐generated oxidants. The generation, storage, and release of oxidants from the PTH are assessed. The efficacy of the alginate PTH in cancer treatment is demonstrated in the context of cancer cell cytotoxicity and immunogenicity–release of danger signals and phagocytosis by immature dendritic cells, up to now unexplored for PTH. These are shown in osteosarcoma, a hard‐to‐treat cancer. The study aims to consolidate PTH as a novel cold plasma treatment modality for non‐invasive or postoperative tumor treatment. The results offer a rationale for further exploration of alginate‐based PTHs as a versatile platform in biomedical engineering.

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Thermosensitive hydrogels to deliver reactive species generated by cold atmospheric plasma: a case study with methylcellulose

Abstract: Hydrogels have been recently proposed as suitable materials to generate reactive oxygen and nitrogen species (RONS) upon gas-plasma treatment, and postulated as promising alternatives to conventional cancer therapies.

Cited by 14 publications

References 50 publications

d-Glucose Oxidation by Cold Atmospheric Plasma-Induced Reactive Species

d-Glucose Oxidation by Cold Atmospheric Plasma-Induced Reactive Species

Current State of Cold Atmospheric Plasma and Cancer‐Immunity Cycle: Therapeutic Relevance and Overcoming Clinical Limitations Using Hydrogels

Injectable Plasma‐Treated Alginate Hydrogel for Oxidative Stress Delivery to Induce Immunogenic Cell Death in Osteosarcoma

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