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Antioxidants
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When the Anticancer Strategies Modulating Oxidative Stress Meet Nanomedicine: New...
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When the Anticancer Strategies Modulating Oxidative Stress Meet Nanomedicine: New Perspectives

A special issue of Antioxidants (ISSN 2076-3921).

Deadline for manuscript submissions: closed (31 January 2020) | Viewed by 21837

Special Issue Editors

Dr. Stefania Pizzimenti

E-Mail Website
Guest Editor
Department of Clinical and Biological Sciences, University of Turin, 10125 Turin, Italy
Interests: lipid peroxidation; oxidative stress; cancer; chemoresistance; resistance to targeted therappies; melanoma; nanomedicine
Special Issues, Collections and Topics in MDPI journals
Dr. Monica Argenziano

E-Mail Website
Guest Editor
Department of Drug Science and Technology, University of Turin, Turin, Italy
Interests: drug delivery; nanocarriers; topical delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear colleagues,

Although contradictory findings have been reported, the link between oxidative stress and tumours has become more and more evident in the last decades. Cancer cells exhibit elevated reactive oxygen species (ROS) levels, which can contribute, with different mechanisms, to the malignant transformation and progression of tumours. ROS scavenging compounds have been used in chemoprevention and at the early stage of treating tumours. However, very conflicting results have been obtained, so the use of antioxidants in cancer prevention needs to be carefully evaluated. On the other hand, the induction of oxidative stress can be toxic to cancer cells, potentially inducing apoptotic cell death. Thus, strategies with the goal of increasing the ROS level, directly, with prooxidant drugs (e.g. doxorubicin, menadione), or indirectly, by lowering the cellular antioxidant defences, have been used for effective cancer therapies.

Advances in the developing field of nanomedicine can further expand the possibilities of redox-anticancer treatments. Indeed, the use of nanoparticles (NPs) offers many advantages as drug carrier system, by improving the solubility of poorly water-soluble drugs, increasing drug half-life, improving bioavailability and diminishing the drug metabolism. Both antioxidant and pro-oxidant NPs (containing compounds that can reduce or enhance oxidative stress, respectively), as well as redox-sensitive NPs (in most cases containing disulfide bonds to achieve a stimuli-responsive drug release) have been investigated in cancer therapy. Moreover NPs per se can be redox active (e.g. cerium oxide/nanoceria), thus expanding the potential for their therapeutic use.

This Special Issue welcomes original research and reviews of literature concerning tumour chemoprevention and cancer progression studies of redox nanosystems, such as NPs per se redox active or containing conventional chemotherapic medicines, new alternative compounds, molecularly targeted cancer drugs, or nucleic acids with both antioxidant or pro-oxidant properties, as well as redox stimulus-responsive nanocarriers.

Dr. Stefania Pizzimenti
Dr. Monica Argenziano
Guest Editors

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. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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

  • Antioxidants
  • Reactive oxygen species (ROS)
  • Glutathione (GSH)
  • Nuclear factor erythroid 2-related factor 2 (Nrf2)
  • Redox signalling pathways
  • Chemoresistance
  • Transformation
  • Tumour progression
  • Nanomedicine
  • Nanoparticles
  • Redox-sensitive nanoparticles

Published Papers (6 papers)

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Research

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16 pages, 5878 KiB  
Article
Carbosilane Dendrimers Loaded with siRNA Targeting Nrf2 as a Tool to Overcome Cisplatin Chemoresistance in Bladder Cancer Cells
by Leanne Ambrosio, Monica Argenziano, Marie Angèle Cucci, Margherita Grattarola, Inge A.M. de Graaf, Chiara Dianzani, Giuseppina Barrera, Javier Sánchez Nieves, Rafael Gomez, Roberta Cavalli and Stefania Pizzimenti
Antioxidants 2020, 9(10), 993; https://doi.org/10.3390/antiox9100993 - 14 Oct 2020
Cited by 21 | Viewed by 2748
Abstract
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as the master regulator of antioxidant and cytoprotective gene expressions. Moreover, it plays a pivotal role in cancer progression. Nrf2 mediates the adaptive response which contributes to the resistance to chemotherapeutic [...] Read more.
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as the master regulator of antioxidant and cytoprotective gene expressions. Moreover, it plays a pivotal role in cancer progression. Nrf2 mediates the adaptive response which contributes to the resistance to chemotherapeutic pro-oxidant drugs, such as cisplatin (CDDP), in various tumors, including bladder cancers. For this reason, Nrf2 could be a promising target to overcome chemoresistance. There are several known Nrf2 pharmacological inhibitors; however, most of them are not specific. The use of a specific small interfering RNA (siRNA) targeting the Nrf2 gene (siNrf2) loaded into nanovehicles is an attractive alternative, since it can increase specificity. This study aimed to evaluate the biological activity of siNrf2 loaded on guanidine-terminated carbosilane dendrimers (GCDs) in overcoming CDDP resistance in bladder cancer cells with a high level of Nrf2. Parameters such as viability, proliferation, apoptosis, migration, and oxidative stress level were taken into account. Results demonstrated that siNrf2-GCD treatment sensitized CDDP-resistant cells to CDDP treatment. Moreover, data obtained by treating the non-cancerous human kidney HK-2 cell line strongly suggest a good safety profile of the carbosilane dendrimers loaded with siNrf2. In conclusion, we suggest that siNrf2-GCD is a promising drug delivery system for gene therapy to be used in vivo; and it may represent an important tool in the therapy of CDDP-resistant cancer. Full article
(This article belongs to the Special Issue When the Anticancer Strategies Modulating Oxidative Stress Meet Nanomedicine: New Perspectives)
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13 pages, 4141 KiB  
Article
Polyurea Dendrimer Folate-Targeted Nanodelivery of l-Buthionine Sulfoximine as a Tool to Tackle Ovarian Cancer Chemoresistance
by Adriana Cruz, Pedro Mota, Cristiano Ramos, Rita F. Pires, Cindy Mendes, José P. Silva, Sofia C. Nunes, Vasco D. B. Bonifácio and Jacinta Serpa
Antioxidants 2020, 9(2), 133; https://doi.org/10.3390/antiox9020133 - 03 Feb 2020
Cited by 22 | Viewed by 3123
Abstract
Ovarian cancer is a highly lethal disease, mainly due to chemoresistance. Our previous studies on metabolic remodeling in ovarian cancer have supported that the reliance on glutathione (GSH) bioavailability is a main adaptive metabolic mechanism, also accounting for chemoresistance to conventional therapy based [...] Read more.
Ovarian cancer is a highly lethal disease, mainly due to chemoresistance. Our previous studies on metabolic remodeling in ovarian cancer have supported that the reliance on glutathione (GSH) bioavailability is a main adaptive metabolic mechanism, also accounting for chemoresistance to conventional therapy based on platinum salts. In this study, we tested the effects of the in vitro inhibition of GSH synthesis on the restoration of ovarian cancer cells sensitivity to carboplatin. GSH synthesis was inhibited by exposing cells to l-buthionine sulfoximine (l-BSO), an inhibitor of γ-glutamylcysteine ligase (GCL). Given the systemic toxicity of l-BSO, we developed a new formulation using polyurea (PURE) dendrimers nanoparticles (l-BSO@PUREG4-FA2), targeting l-BSO delivery in a folate functionalized nanoparticle. Full article
(This article belongs to the Special Issue When the Anticancer Strategies Modulating Oxidative Stress Meet Nanomedicine: New Perspectives)
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23 pages, 4070 KiB  
Article
Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells
by Silvana Alfei, Barbara Marengo and Cinzia Domenicotti
Antioxidants 2020, 9(1), 50; https://doi.org/10.3390/antiox9010050 - 06 Jan 2020
Cited by 30 | Viewed by 3625
Abstract
Etoposide (ETO) is a cytotoxic drug that exerts its effect by increasing reactive oxygen species (ROS) production. Although ETO is widely used, fast metabolism, poor solubility, systemic toxicity, and multi-drug resistance induction all limit its administration dosage and its therapeutic efficiency. In order [...] Read more.
Etoposide (ETO) is a cytotoxic drug that exerts its effect by increasing reactive oxygen species (ROS) production. Although ETO is widely used, fast metabolism, poor solubility, systemic toxicity, and multi-drug resistance induction all limit its administration dosage and its therapeutic efficiency. In order to address these issues, a biodegradable dendrimer was prepared for entrapping and protecting ETO and for enhancing its solubility and effectiveness. The achieved dendrimer complex with ETO (CPX 5) showed the typical properties of a well-functioning delivery system, i.e., nanospherical morphology (70 nm), optimal Z-potential (−45 mV), good drug loading (37%), very satisfying entrapment efficiency (53%), and a remarkably improved solubility in biocompatible solvents. In regards to its cytotoxic activity, CPX 5 was tested on neuroblastoma (NB) cells with very promising results. In fact, the dendrimer scaffold and ETO are able to exert per se a cytotoxic and pro-oxidant activity on human NB cells. When CPX 5 is combined with ETO, it shows a synergistic action, slowly releasing the drug over time and significantly improving and protracting bioactivity. On the basis of these findings, the prepared ETO reservoir represents a novel biodegradable and promising device for the delivery of ETO into NB cells. Full article
(This article belongs to the Special Issue When the Anticancer Strategies Modulating Oxidative Stress Meet Nanomedicine: New Perspectives)
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15 pages, 2892 KiB  
Article
Silver Nanoparticles Induce Mitochondrial Protein Oxidation in Lung Cells Impacting Cell Cycle and Proliferation
by Reetta J. Holmila, Stephen A. Vance, Stephen Bruce King, Allen W. Tsang, Ravi Singh and Cristina M. Furdui
Antioxidants 2019, 8(11), 552; https://doi.org/10.3390/antiox8110552 - 14 Nov 2019
Cited by 45 | Viewed by 4166
Abstract
Silver nanoparticles (AgNPs) are widely used nanomaterials in both commercial and clinical biomedical applications, due to their antibacterial properties. AgNPs are also being explored for the treatment of cancer in particular in combination with ionizing radiation. In this work, we studied the effects [...] Read more.
Silver nanoparticles (AgNPs) are widely used nanomaterials in both commercial and clinical biomedical applications, due to their antibacterial properties. AgNPs are also being explored for the treatment of cancer in particular in combination with ionizing radiation. In this work, we studied the effects of AgNPs and ionizing radiation on mitochondrial redox state and function in a panel of lung cell lines (A549, BEAS-2B, Calu-1 and NCI-H358). The exposure to AgNPs caused cell cycle arrest and decreased cell proliferation in A549, BEAS-2B and Calu-1, but not in NCI-H358. The mitochondrial reactive oxygen species (ROS) and protein oxidation increased in a time- and dose-dependent manner in the more sensitive cell lines with the AgNP exposure, but not in NCI-H358. While ionizing radiation also induced changes in the mitochondrial redox profiles, in general, these were not synergistic with the effects of AgNPs with the exception of NCI-H358 and only at a higher dose of radiation. Full article
(This article belongs to the Special Issue When the Anticancer Strategies Modulating Oxidative Stress Meet Nanomedicine: New Perspectives)
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Review

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16 pages, 785 KiB  
Review
Utilizing Iron for Targeted Lipid Peroxidation as Anticancer Option of Integrative Biomedicine: A Short Review of Nanosystems Containing Iron
by Morana Jaganjac, Suzana Borovic Sunjic and Neven Zarkovic
Antioxidants 2020, 9(3), 191; https://doi.org/10.3390/antiox9030191 - 25 Feb 2020
Cited by 22 | Viewed by 3884
Abstract
Traditional concepts of life sciences consider oxidative stress as a fundamental process of aging and various diseases including cancer, whereas traditional medicine recommends dietary intake of iron to support physiological functions of the organism. However, due to its strong pro-oxidative capacity, if not [...] Read more.
Traditional concepts of life sciences consider oxidative stress as a fundamental process of aging and various diseases including cancer, whereas traditional medicine recommends dietary intake of iron to support physiological functions of the organism. However, due to its strong pro-oxidative capacity, if not controlled well, iron can trigger harmful oxidative stress manifested eventually by toxic chain reactions of lipid peroxidation. Such effects of iron are considered to be major disadvantages of uncontrolled iron usage, although ferroptosis seems to be an important defense mechanism attenuating cancer development. Therefore, a variety of iron-containing nanoparticles were developed for experimental radio-, chemo-, and photodynamic as well as magnetic dynamic nanosystems that alter redox homeostasis in cancer cells. Moreover, studies carried over recent decades have revealed that even the end products of lipid peroxidation, represented by 4-hydroxynonenal (4-HNE), could have desirable effects even acting as kinds of selective anticancer substances produced by non-malignant cells for defense again invading cancer. Therefore, advanced nanotechnologies should be developed for using iron to trigger targeted lipid peroxidation as an anticancer option of integrative biomedicine. Full article
(This article belongs to the Special Issue When the Anticancer Strategies Modulating Oxidative Stress Meet Nanomedicine: New Perspectives)
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Other

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11 pages, 539 KiB  
Opinion
Nanoparticles as Tools to Target Redox Homeostasis in Cancer Cells
by Francesco Ciccarese, Vittoria Raimondi, Evgeniya Sharova, Micol Silic-Benussi and Vincenzo Ciminale
Antioxidants 2020, 9(3), 211; https://doi.org/10.3390/antiox9030211 - 04 Mar 2020
Cited by 35 | Viewed by 3693
Abstract
Reactive oxygen species (ROS) constitute a homeostatic rheostat that modulates signal transduction pathways controlling cell turnover. Most oncogenic pathways activated in cancer cells drive a sustained increase in ROS production, and cancer cells are strongly addicted to the increased activity of scavenging pathways [...] Read more.
Reactive oxygen species (ROS) constitute a homeostatic rheostat that modulates signal transduction pathways controlling cell turnover. Most oncogenic pathways activated in cancer cells drive a sustained increase in ROS production, and cancer cells are strongly addicted to the increased activity of scavenging pathways to maintain ROS below levels that produce macromolecular damage and engage cell death pathways. Consistent with this notion, tumor cells are more vulnerable than their normal counterparts to pharmacological treatments that increase ROS production and inhibit ROS scavenging. In the present review, we discuss the recent advances in the development of integrated anticancer therapies based on nanoparticles engineered to kill cancer cells by raising their ROS setpoint. We also examine nanoparticles engineered to exploit the metabolic and redox alterations of cancer cells to promote site-specific drug delivery to cancer cells, thus maximizing anticancer efficacy while minimizing undesired side effects on normal tissues. Full article
(This article belongs to the Special Issue When the Anticancer Strategies Modulating Oxidative Stress Meet Nanomedicine: New Perspectives)
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