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Reactive Oxygen Species (ROS): Molecular Mechanisms and Therapeutic Strategy

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 7602

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Special Issue Editor

Dr. Young-Il Jeong

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Guest Editor

Biomedical R&D Center, Pusan National University Yangsan Hospital, 43241 Pusan, Republic of Korea
Interests: cancer; reactive oxygen species; nanomedicine; anticancer agents; drug-delivery system; ROS-sensitive nanomaterials; photodynamic therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Reactive oxygen species (ROS), which are in a chemically active state, are a byproduct of the metabolism of oxygen in cells. They play critical roles in molecular mechanisms in cellular signaling processes, proliferation/migration and homeostasis. Furthermore, the molecular mechanism of ROS is a double-edged sword. Appropriate levels of intracellular ROS contribute to the proliferation, migration and/or homeostasis of cells, while their over-production frequently induces cell cycle arrest, apoptosis, necrosis and/or alterations of genetic/cell structure.

These unique properties of ROS have been investigated as a therapeutic tool for various diseases. For example, novel chemotherapeutic agents, which produce ROS, can be used to induce oxidative stress intracellularly and then kill abnormal cells. Additionally, ROS-producing agents can be used as anticancer agents for cancer chemotherapy.

In this Special Issue, topics include, but are not limited to:

Molecular mechanisms of intracellular oxidative stress;
Intracellular ROS generation and its role in cells;
ROS-producing chemicals as therapeutic agents;
ROS-sensitive nanomaterials and drug-delivery systems;
ROS-mediated diagnosis of disease;
Photodynamic therapy.

Dr. Jeong Young-IL
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

reactive oxygen species (ROS)
oxidative stress
cell signaling
ROS-producing agent
ROS-sensitive materials
cancer chemotherapy
photodynamic therapy
cold atmospheric plasma

Published Papers (3 papers)

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Research

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14 pages, 5162 KiB

Open AccessArticle

Redox-Sensitive Delivery of Doxorubicin from Nanoparticles of Poly(ethylene glycol)-Chitosan Copolymer for Treatment of Drug-Resistant Oral Cancer Cells

by Kaengwon Yoon, Seunggon Jung, Jaeyoung Ryu, Hong-Ju Park, Hee-Kyun Oh and Min-Suk Kook

Int. J. Mol. Sci. 2023, 24(18), 13704; https://doi.org/10.3390/ijms241813704 - 5 Sep 2023

Cited by 1 | Viewed by 898

Abstract

Reactive oxygen species (ROS)-sensitive polymer nanoparticles were synthesized for tumor targeting of an anticancer drug, doxorubicin (DOX). For this purpose, chitosan-methoxy poly(ethylene glycol) (mPEG) (ChitoPEG)-graft copolymer was synthesized and then DOX was conjugated to the backbone of chitosan using a thioketal linker. Subsequently, the chemical structure of the DOX-conjugated ChitoPEG copolymer (ChitoPEGthDOX) was confirmed via ¹H nuclear magnetic resonance (NMR) spectra. Nanoparticles of the ChitoPEGthDOX conjugates have spherical shapes and a size of approximately 100 nm. Transmission electron microscopy (TEM) has shown that ChitoPEGthDOX nanoparticles disintegrate in the presence of hydrogen peroxide and the particle size distribution also changes from a monomodal/narrow distribution pattern to a multi-modal/wide distribution pattern. Furthermore, DOX is released faster in the presence of hydrogen peroxide. These results indicated that ChitoPEGthDOX nanoparticles have ROS sensitivity. The anticancer activity of the nanoparticles was evaluated using AT84 oral squamous carcinoma cells. Moreover, DOX-resistant AT84 cells were prepared in vitro. DOX and its nanoparticles showed dose-dependent cytotoxicity in both DOX-sensitive and DOX-resistant AT84 cells in vitro. However, DOX itself showed reduced cytotoxicity against DOX-resistant AT84 cells, while the nanoparticles showed almost similar cytotoxicity to DOX-sensitive and DOX-resistant AT84 cells. This result may be due to the inhibition of intracellular delivery of free DOX, while nanoparticles were efficiently internalized in DOX-resistant cells. The in vivo study of a DOX-resistant AT84 cell-bearing tumor xenograft model showed that nanoparticles have higher antitumor efficacy than those found in free DOX treatment. These results may be related to the efficient accumulation of nanoparticles in the tumor tissue, i.e., the fluorescence intensity in the tumor tissue was stronger than that of any other organs. Our findings suggest that ChitoPEGthDOX nanoparticles may be a promising candidate for ROS-sensitive anticancer delivery against DOX-resistant oral cancer cells. Full article

(This article belongs to the Special Issue Reactive Oxygen Species (ROS): Molecular Mechanisms and Therapeutic Strategy)

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22 pages, 31839 KiB

Open AccessArticle

A Photoactivated Ru (II) Polypyridine Complex Induced Oncotic Necrosis of A549 Cells by Activating Oxidative Phosphorylation and Inhibiting DNA Synthesis as Revealed by Quantitative Proteomics

by Li Zhu, Hui Liu, Yang Dou, Qun Luo, Liangzhen Gu, Xingkai Liu, Qianxiong Zhou, Juanjuan Han and Fuyi Wang

Int. J. Mol. Sci. 2023, 24(9), 7756; https://doi.org/10.3390/ijms24097756 - 24 Apr 2023

Cited by 2 | Viewed by 1859

Abstract

The ruthenium polypyridine complex [Ru(dppa)₂(pytp)] (PF₆)₂ (termed as ZQX-1), where dppa = 4,7-diphenyl-1,10-phenanthroline and pytp = 4′-pyrene-2,2′:6′,2′′-terpyridine, has been shown a high and selective cytotoxicity to hypoxic and cisplatin-resistant cancer cells either under irradiation with blue light or upon two-photon excitation. The IC₅₀ values of ZQX-1 towards A549 cancer cells and HEK293 health cells are 0.16 ± 0.09 µM and >100 µM under irradiation at 420 nm, respectively. However, the mechanism of action of ZQX-1 remains unclear. In this work, using the quantitative proteomics method we identified 84 differentially expressed proteins (DEPs) with |fold-change| ≥ 1.2 in A549 cancer cells exposed to ZQX-1 under irradiation at 420 nm. Bioinformatics analysis of the DEPs revealed that photoactivated ZQX-1 generated reactive oxygen species (ROS) to activate oxidative phosphorylation signaling to overproduce ATP; it also released ROS and pyrene derivative to damage DNA and arrest A549 cells at S-phase, which synergistically led to oncotic necrosis and apoptosis of A549 cells to deplete excess ATP, evidenced by the elevated level of PRAP1 and cleaved capase-3. Moreover, the DNA damage inhibited the expression of DNA repair-related proteins, such as RBX1 and GPS1, enhancing photocytotoxicity of ZQX-1, which was reflected in the inhibition of integrin signaling and disruption of ribosome assembly. Importantly, the photoactivated ZQX-1 was shown to activate hypoxia-inducible factor 1A (HIF1A) survival signaling, implying that combining use of ZQX-1 with HIF1A signaling inhibitors may further promote the photocytotoxicity of the prodrug. Full article

(This article belongs to the Special Issue Reactive Oxygen Species (ROS): Molecular Mechanisms and Therapeutic Strategy)

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Review

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24 pages, 2641 KiB

Open AccessReview

The Effectiveness of L-arginine in Clinical Conditions Associated with Hypoxia

by Natalia Kurhaluk

Int. J. Mol. Sci. 2023, 24(9), 8205; https://doi.org/10.3390/ijms24098205 - 3 May 2023

Cited by 7 | Viewed by 4209

Abstract

The review summarises the data of the last 50 years on the effectiveness of the amino acid L-arginine in therapeutic practice in conditions accompanied by different-origin hypoxia. The aim of this review was to analyse the literature and our research data on the role of nitric oxide in the modulation of individual physiological reactivity to hypoxia. The review considers the possibility of eliminating methodological conflicts in the case of L-arginine, which can be solved by taking into account individual physiological reactivity (or the hypoxia resistance factor). Considerable attention is paid to genetic and epigenetic mechanisms of adaptation to hypoxia and conditions of adaptation in different models. The article presents data on the clinical effectiveness of L-arginine in cardiovascular system diseases (hypertension, atherosclerosis, coronary heart disease, etc.) and stress disorders associated with these diseases. The review presents a generalised analysis of techniques, data on L-arginine use by athletes, and the ambiguous role of NO in the physiology and pathology of hypoxic states shown via nitric oxide synthesis. Data on the protective effects of adaptation in the formation of individual high reactivity in sportsmen are demonstrated. The review demonstrates a favourable effect of supplementation with L-arginine and its application depending on mitochondrial oxidative phosphorylation processes and biochemical indices in groups of individuals with low and high capacity of adaptation to hypoxia. In individuals with high initial anti-hypoxic reserves, these favourable effects are achieved by the blockade of NO-dependent biosynthesis pathways. Therefore, the methodological tasks of physiological experiments and the therapeutic consequences of treatment should include a component depending on the basic level of physiological reactivity. Full article

(This article belongs to the Special Issue Reactive Oxygen Species (ROS): Molecular Mechanisms and Therapeutic Strategy)

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