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Reactive Oxygen Species—Related Materials and Medicine

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 21908

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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, Pusan 43241, 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

Reactive oxygen species (ROS) such as peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen are under a chemically reactive state. Even though ROS are a byproduct from the metabolism of oxygen in cells, they play a critical role in cellular signaling process and homeostasis. Especially the biological roles of ROS are a double-edged sword. When ROS exist in cells within the appropriate level, they frequently contribute to the proliferation, migration, and homeostasis of cells. However, excessive levels of ROS normally induce cell cycle arrest, apoptosis, necrosis or genetic alterations in biological systems and then affect the structure of cells.

From this point of view, many types of scientists, such as molecular biologists, have been investigating the molecular process of ROS production and their action in normal cells or cancer cells, while other scientists have been developing novel medicines and nanomaterials that produce ROS or are modified by ROS. For example, ROS-producing agents and/or ROS-sensitive nanomaterials in chemotherapeutic approaches are to produce excessive ROS in cells and kill the cancer cells. ROS generation in cells is increasingly finding itself in the spotlight in various fields of science.

Some of the topics around reactive oxygen species to be tackled in this Special Issue include but are not limited to:

- Molecular mechanism of ROS generation and its action in cells;

- ROS-producing agents;

- ROS-sensitive nanomaterials;

- ROS-mediated drug delivery system;

- ROS-mediated diagnosis of disease;

- Photodynamic therapy.

Prof. Jeong Young-IL
Guest Editor

Manuscript Submission Information

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Keywords

Reactive oxygen species (ROS)
ROS-producing agents
ROS-sensitive nanomaterials
ROS-mediated drug delivery system
ROS-mediated diagnosis of disease
Molecular mechanism of ROS generation and its action in cells

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Published Papers (6 papers)

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Research

18 pages, 6090 KiB

Open AccessArticle

The Effect of Oxidative Stress and Memantine-Incorporated Reactive Oxygen Species-Sensitive Nanoparticles on the Expression of N-Methyl-d-aspartate Receptor Subunit 1 in Brain Cancer Cells for Alzheimer’s Disease Application

by Jung Sun Park, Taeyeon Kim, Dohoon Kim and Young-IL Jeong

Int. J. Mol. Sci. 2021, 22(22), 12309; https://doi.org/10.3390/ijms222212309 - 15 Nov 2021

Cited by 8 | Viewed by 3871

Abstract

The aim of this study is to fabricate reactive oxygen species (ROS)-sensitive nanoparticles composed of succinyl β-cyclodextrin (bCDsu), memantine and thioketal linkages for application in Alzheimer’s disease, and to investigate the suppression of N-methyl-d-aspartate (NMDA) receptor 1 (NMDAR1) in cells. Thioketal diamine was attached to the carboxyl group of bCDsu to produce thioketal-decorated bCDsu conjugates (bCDsu-thioketal conjugates) and memantine was conjugated with thioketal dicarboxylic acid (memantine-thioketal carboxylic acid conjugates). Memantine-thioketal carboxylic acid conjugates were attached to bCDsu-thioketal conjugates to produce bCDsu-thioketal-memantine (bCDsuMema) conjugates. SH-SY5Y neuroblastoma cells and U87MG cells were used for NMDAR1 protein expression and cellular oxidative stress. Nanoparticles of bCDsuMema conjugates were prepared by means of a dialysis procedure. Nanoparticles of bCDsuMema conjugates had small particle sizes less than 100 nm and their morphology was found to be spherical in transmission electron microscopy observations (TEM). Nanoparticles of bCDsuMema conjugates responded to H₂O₂ and disintegrated or swelled in aqueous solution. Then, the nanoparticles rapidly released memantine according to the concentration of H₂O₂. In an in vivo animal imaging study, thioketal-decorated nanoparticles labelled with fluorescent dye such as chlorin e6 (Ce6) showed that the fluorescence intensity was stronger in the brain than in other organs, indicating that bCDsuMema nanoparticles can efficiently target the brain. When cells were exposed to H₂O₂, the viability of cells was time-dependently decreased. Memantine or bCDsuMema nanoparticles did not practically affect the viability of the cells. Furthermore, a western blot assay showed that the oxidative stress produced in cells using H₂O₂ increased the expression of NMDAR1 protein in both SH-SY5Y and U87MG cells. Memantine or bCDsuMema nanoparticles efficiently suppressed the NMDAR1 protein, which is deeply associated with Alzheimer’s disease. Fluorescence microscopy also showed that H₂O₂ treatment induced green fluorescence intensity, which represents intracellular ROS levels. Furthermore, H₂O₂ treatment increased the red fluorescence intensity, which represents the NMDAR1 protein, i.e., oxidative stress increases the expression of NMDAR1 protein level in both SH-SY5Y and U87MG cells. When memantine or bCDsuMema nanoparticles were treated in cells, the oxidative stress-mediated expression of NMDAR1 protein in cells was significantly decreased, indicating that bCDsuMema nanoparticles have the capacity to suppress NMDAR1 expression in brain cells, which has relevance in terms of applications in Alzheimer’s disease. Full article

(This article belongs to the Special Issue Reactive Oxygen Species—Related Materials and Medicine)

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16 pages, 3668 KiB

Open AccessArticle

Caffeic Acid Phenethyl Ester-Incorporated Radio-Sensitive Nanoparticles of Phenylboronic Acid Pinacol Ester-Conjugated Hyaluronic Acid for Application in Radioprotection

by Seon-Hee Choi, Dong-Yeon Lee, Sohi Kang, Min-Kyung Lee, Jae-Heun Lee, Sang-Heon Lee, Hye-Lim Lee, Hyo-Young Lee and Young-IL Jeong

Int. J. Mol. Sci. 2021, 22(12), 6347; https://doi.org/10.3390/ijms22126347 - 14 Jun 2021

Cited by 10 | Viewed by 3217

Abstract

We synthesized phenylboronic acid pinacol ester (PBPE)-conjugated hyaluronic acid (HA) via thiobis(ethylamine) (TbEA) linkage (abbreviated as HAsPBPE conjugates) to fabricate the radiosensitive delivery of caffeic acid phenetyl ester (CAPE) and for application in radioprotection. PBPE was primarily conjugated with TbEA and then PBPE-TbEA conjugates were conjugated again with hyaluronic acid using carbodiimide chemistry. CAPE-incorporated nanoparticles of HAsPBPE were fabricated by the nanoprecipitation method and then the organic solvent was removed by dialysis. CAPE-incorporated HAsPBPE nanoparticles have a small particle size of about 80 or 100 nm and they have a spherical shape. When CAPE-incorporated HAsPBPE nanoparticles were irradiated, nanoparticles became swelled or disintegrated and their morphologies were changed. Furthermore, the CAPE release rate from HAsPBPE nanoparticles were increased according to the radiation dose, indicating that CAPE-incorporated HAsPBPE nanoparticles have radio-sensitivity. CAPE and CAPE-incorporated HAsPBPE nanoparticles appropriately prevented radiation-induced cell death and suppressed intracellular accumulation of reactive oxygen species (ROS). CAPE and CAPE-incorporated HAsPBPE nanoparticles efficiently improved survivability of mice from radiation-induced death and reduced apoptotic cell death. We suggest that HAsPBPE nanoparticles are promising candidates for the radio-sensitive delivery of CAPE. Full article

(This article belongs to the Special Issue Reactive Oxygen Species—Related Materials and Medicine)

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20 pages, 8782 KiB

Open AccessArticle

Dichloroacetate Radiosensitizes Hypoxic Breast Cancer Cells

by Sven de Mey, Inès Dufait, Heng Jiang, Cyril Corbet, Hui Wang, Melissa Van De Gucht, Lisa Kerkhove, Ka Lun Law, Hugo Vandenplas, Thierry Gevaert, Olivier Feron and Mark De Ridder

Int. J. Mol. Sci. 2020, 21(24), 9367; https://doi.org/10.3390/ijms21249367 - 9 Dec 2020

Cited by 19 | Viewed by 4851

Abstract

Mitochondrial metabolism is an attractive target for cancer therapy. Reprogramming metabolic pathways can potentially sensitize tumors with limited treatment options, such as triple-negative breast cancer (TNBC), to chemo- and/or radiotherapy. Dichloroacetate (DCA) is a specific inhibitor of the pyruvate dehydrogenase kinase (PDK), which leads to enhanced reactive oxygen species (ROS) production. ROS are the primary effector molecules of radiation and an increase hereof will enhance the radioresponse. In this study, we evaluated the effects of DCA and radiotherapy on two TNBC cell lines, namely EMT6 and 4T1, under aerobic and hypoxic conditions. As expected, DCA treatment decreased phosphorylated pyruvate dehydrogenase (PDH) and lowered both extracellular acidification rate (ECAR) and lactate production. Remarkably, DCA treatment led to a significant increase in ROS production (up to 15-fold) in hypoxic cancer cells but not in aerobic cells. Consistently, DCA radiosensitized hypoxic tumor cells and 3D spheroids while leaving the intrinsic radiosensitivity of the tumor cells unchanged. Our results suggest that although described as an oxidative phosphorylation (OXPHOS)-promoting drug, DCA can also increase hypoxic radioresponses. This study therefore paves the way for the targeting of mitochondrial metabolism of hypoxic cancer cells, in particular to combat radioresistance. Full article

(This article belongs to the Special Issue Reactive Oxygen Species—Related Materials and Medicine)

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15 pages, 17772 KiB

Open AccessArticle

Are Metal Ions That Make up Orthodontic Alloys Cytotoxic, and Do They Induce Oxidative Stress in a Yeast Cell Model?

by Vito Kovač, Borut Poljšak, Jasmina Primožič and Polona Jamnik

Int. J. Mol. Sci. 2020, 21(21), 7993; https://doi.org/10.3390/ijms21217993 - 27 Oct 2020

Cited by 17 | Viewed by 2676

Abstract

Compositions of stainless steel, nickel-titanium, cobalt-chromium and β-titanium orthodontic alloys were simulated with mixtures of Fe, Ni, Cr, Co, Ti and Mo metal ions as potential oxidative stress-triggering agents. Wild-type yeast Saccharomyces cerevisiae and two mutants ΔSod1 and ΔCtt1 were used as model organisms to assess the cytotoxicity and oxidative stress occurrence. Metal mixtures at concentrations of 1, 10, 100 and 1000 µM were prepared out of metal chlorides and used to treat yeast cells for 24 h. Every simulated orthodontic alloy at 1000 µM was cytotoxic, and, in the case of cobalt-chromium alloy, even 100 µM was cytotoxic. Reactive oxygen species and oxidative damage were detected for stainless steel and both cobalt-chromium alloys at 1000 µM in wild-type yeast and 100 µM in the ΔSod1 and ΔCtt1 mutants. Simulated nickel-titanium and β-titanium alloy did not induce oxidative stress in any of the tested strains. Full article

(This article belongs to the Special Issue Reactive Oxygen Species—Related Materials and Medicine)

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15 pages, 4335 KiB

Open AccessArticle

Combinatorial Effect of Cold Atmosphere Plasma (CAP) and the Anticancer Drug Cisplatin on Oral Squamous Cell Cancer Therapy

by Chang-Min Lee, Young-IL Jeong, Min-Suk Kook and Byung-Hoon Kim

Int. J. Mol. Sci. 2020, 21(20), 7646; https://doi.org/10.3390/ijms21207646 - 15 Oct 2020

Cited by 33 | Viewed by 2790

Abstract

Cold atmospheric plasma (CAP) has been extensively investigated in the local treatment of cancer due to its potential of reactive oxygen species (ROS) generation in biological systems. In this study, we examined the synergistic effect of combination of CAP and cisplatin-mediated chemotherapy of oral squamous cell carcinoma (OSCC) in vitro. SCC-15 OSCC cells and human gingival fibroblasts (HGF-1) cells were treated with cisplatin, and then, the cells were irradiated with CAP. Following this, viability and apoptosis behavior of the cells were investigated. The viability of SCC-15 cells was inhibited by cisplatin with a dose-dependent manner and CAP treatment time. HGF-1 cells also showed decreased viability by treatment with cisplatin and CAP. Combination of 1 μM cisplatin plus 3 min of CAP treatment or 3 μM cisplatin plus 1 min of CAP treatment showed a synergistic anticancer effect with appropriate cytotoxicity against normal cells. ROS generation and dead cell staining were also increased by the increase in CAP treatment time. Furthermore, tumor-suppressor proteins and apoptosis-related enzymes also increased according to the treatment time of CAP. We showed the synergistic effect of cisplatin and CAP treatment against SCC-15 cells with low cytotoxicity against normal cells. Full article

(This article belongs to the Special Issue Reactive Oxygen Species—Related Materials and Medicine)

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17 pages, 1607 KiB

Open AccessArticle

Resveratrol Delivery from Implanted Cyclodextrin Polymers Provides Sustained Antioxidant Effect on Implanted Neural Probes

by Rebecca M. Haley, Sean T. Zuckerman, Hassan Dakhlallah, Jeffery R. Capadona, Horst A. von Recum and Evon S. Ereifej

Int. J. Mol. Sci. 2020, 21(10), 3579; https://doi.org/10.3390/ijms21103579 - 19 May 2020

Cited by 20 | Viewed by 3360

Abstract

Intracortical microelectrodes are valuable tools used to study and treat neurological diseases. Due in large part to the oxidative stress and inflammatory response occurring after electrode implantation, the signal quality of these electrodes decreases over time. To alleviate this response, resveratrol, a natural antioxidant which elicits neuroprotective effects through reduction of oxidative stress, was utilized. This work compares traditional systemic delivery of resveratrol to the novel cyclodextrin polymer (pCD) local delivery approach presented herein, both in vitro and in vivo. The pCD displayed an extended resveratrol release for 100 days, as well as 60 days of free radical scavenging activity in vitro. In vivo results indicated that our pCD delivery system successfully delivered resveratrol to the brain with a sustained release for the entire short-duration study (up to 7 days). Interestingly, significantly greater concentrations of resveratrol metabolites were found at the intracortical probe implantation site compared to the systemic administration of resveratrol. Together, our pilot results provide support for the possibility of improving the delivery of resveratrol in an attempt to stabilize long-term neural interfacing applications. Full article

(This article belongs to the Special Issue Reactive Oxygen Species—Related Materials and Medicine)

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