Nanotechnology-Based Drug Delivery to Improve the Therapeutic Benefits of NRF2 Modulators in Cancer Therapy

Abstract

The disadvantages of conventional anticancer drugs, such as their low bioavailability, poor targeting efficacy, and serious side effects, have led to the discovery of new therapeutic agents and potential drug delivery systems. In particular, the introduction of nano-sized drug delivery systems (NDDSs) has opened new horizons for effective cancer treatment. These are considered potential systems that provide deep tissue penetration and specific drug targeting. On the other hand, nuclear factor erythroid 2-related factor 2 (NRF2)-based anticancer treatment approaches have attracted tremendous attention and produced encouraging results. However, the lack of effective formulation strategies is one of the factors that hinder the clinical application of NRF2 modulators. In this review, we initially focus on the critical role of NRF2 in cancer cells and NRF2-based anticancer treatment. Subsequently, we review the preparation and characterization of NDDSs encapsulating NRF2 modulators and discuss their potential for cancer therapy.

Polyphenols as Antioxidants for Extending Food Shelf-Life and in the Prevention of Health Diseases: Encapsulation and Interfacial Phenomena

“…Overall studies indicate that microemulsions can increase the oral bioavailability of compounds by paracellular diffusion and lymphatic transport. They also contribute to the stability of molecules by protecting against enzymatic degradation in the gastrointestinal tract [ 46 , 47 ].…”

“…This definitely will allow for an optimal control of the subsequent release of incorporated bioactives in specific sites, allowing for the preparation of target-tailored systems and increasing their efficiency in the biology, medical, pharmaceutical, and cosmetic areas. Certainly, a deeper knowledge on the location and distribution of the bioactives in the system will aid in the development of new delivery systems, not only as nutritional supplements, but also with potential benefits to human health [ 8 , 15 , 47 ].…”

“…Synergistic or antagonistic effects may be observed when two or more antioxidants (AOs) are present at a time, so that their scavenging reactivity is much higher or lower than that of when used alone [ 44 , 45 ]. For example, the couple α-tocopherol/ascorbic acid is synergistic in the inhibition of the lipid oxidation reaction, because tocopherols (primary antioxidants) are replenished from their radicals by ascorbic acid, which is capable of donating hydrogen atoms, inhibiting its depletion [ 46 , 47 ]. Other species that may recover antioxidants include low-molecular-weight thiols and thioethers (methionine, glutathione, acetylcysteine, etc.).…”

“…Currently, the distribution of antioxidants is recognized as a crucial issue regarding their efficiency at inhibiting the oxidation of target biomolecules in multiphasic systems. Current research links the quantitative distribution of antioxidants in complex multiphasic systems with the selection or design of antioxidants that preferentially distribute at the bio-interfaces [ 18 , 47 , 50 ].…”

Nuclear Factor Erythroid-2-Related Factor 2 Signaling in the Neuropathophysiology of Inherited Metabolic Disorders

“…Based on these observations, the modulation of nuclear factor erythroid-2-related factor 2 (Nrf2) signaling pathway has been studied as a therapeutical target for diseases related to oxidative stress and inflammation. Nrf2 modulators, mainly activators, have been already demonstrated to elicit beneficial effects in models of different human pathologies, such as cancer, autoimmune diseases, liver, kidney, and lung diseases, as well as common neurodegenerative disorders ( Adelusi et al, 2020 ; Panieri et al, 2020 ; Scuderi et al, 2020 ; Sharma et al, 2020 ; Kim, 2021 ; Kourakis et al, 2021 ; Sezgin-Bayindir et al, 2021 ; Telkoparan-Akillilar et al, 2021 ; Zhao et al, 2021 ). Of note, some Nrf2 modulators are being currently evaluated in clinical trials for different disorders, such as cancer, neurodegenerative disorders and autoimmune diseases ( Chartoumpekis et al, 2020 ; Panieri et al, 2020 ; Scuderi et al, 2020 ).…”