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      Controlling Morphologies of Redox‐Responsive Polymeric Nanocarriers for a Smart Drug Delivery System

      1 , 2 , 1 , 2
      Chemistry – A European Journal
      Wiley

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          Abstract

          Redox‐responsive nanocarriers using disulfides or thiols have received considerable attention owing to the higher levels of glutathione (GSH) in cancer cells than those in extracellular fluids. Nevertheless, the normal‐to‐cancer‐cell selectivity of these nanocarriers has not yet been clarified. Nanocarriers exhibit different cytotoxicities depending on the morphologies they adopt under the redox‐active conditions typically existing in cancerous cells. Therefore, not only GSH levels but also reactive oxygen species (ROS) levels and other complex cancerous cell conditions must be considered for the development of smart drug delivery systems. In this article, we review the structural design of redox‐responsive polymers that exhibit different morphological changes in environments akin to cancerous cells (e. g., GSH‐ and ROS‐abundant conditions). In addition, we propose a molecular design for the spatiotemporal control of nanocarrier morphology depending on the levels of both GSH and ROS upon photoirradiation to increase the cytotoxicity difference between normal and cancer cells.

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          Analysis of nanoparticle delivery to tumours

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            Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach?

            Increased generation of reactive oxygen species (ROS) and an altered redox status have long been observed in cancer cells, and recent studies suggest that this biochemical property of cancer cells can be exploited for therapeutic benefits. Cancer cells in advanced stage tumours frequently exhibit multiple genetic alterations and high oxidative stress, suggesting that it might be possible to preferentially eliminate these cells by pharmacological ROS insults. However, the upregulation of antioxidant capacity in adaptation to intrinsic oxidative stress in cancer cells can confer drug resistance. Abrogation of such drug-resistant mechanisms by redox modulation could have significant therapeutic implications. We argue that modulating the unique redox regulatory mechanisms of cancer cells might be an effective strategy to eliminate these cells.
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              Mitochondria, oxidants, and aging.

              The free radical theory of aging postulates that the production of intracellular reactive oxygen species is the major determinant of life span. Numerous cell culture, invertebrate, and mammalian models exist that lend support to this half-century-old hypothesis. Here we review the evidence that both supports and conflicts with the free radical theory and examine the growing link between mitochondrial metabolism, oxidant formation, and the biology of aging.
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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                Chemistry – A European Journal
                Chemistry A European J
                Wiley
                0947-6539
                1521-3765
                June 19 2023
                April 27 2023
                June 19 2023
                : 29
                : 34
                Affiliations
                [1 ] Department of Chemistry Ulsan National Institute of Science and Technology (UNIST) Ulsan 4491 Republic of Korea
                [2 ] Center for Wave Energy Materials Ulsan National Institute of Science and Technology (UNIST) Ulsan 44919 Republic of Korea
                Article
                10.1002/chem.202300594
                36974937
                86299915-f617-42bc-9b15-66d1635fdb6e
                © 2023

                http://onlinelibrary.wiley.com/termsAndConditions#vor

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