NADH-Triggered PhotogeneratedCarbon Radicals as GeneralAbstracting Agents for Synergism of Apoptosis and Ferroptosis

Photoinduced Carbene for Effective Photodynamic Therapy Against Hypoxic Cancer Cells

Three birds with one stone: A ferric pyrophosphate based nanoagent for synergetic NIR-triggered photo/chemodynamic therapy with glutathione depletion

Nanophotosensitive drugs for light-based cancer therapy: what does the future hold?

The 2-Cys peroxiredoxins (Prx) belong to a family of antioxidant enzymes that detoxify reactive oxygen and nitrogen species and are distributed throughout the intracellular and extracellular compartments. However, the presence and role of 2-Cys Prxs in the nucleus have not been studied. This study demonstrates that the PrxII located in the nucleus protects cancer cells from DNA damage-induced cell death. Although the two cytosolic 2-Cys Prxs, PrxI and PrxII, were found in the nucleus, only PrxII knockdown selectively and markedly increased cell death in the cancer cells treated with DNA-damaging agents. The increased death was completely reverted by the nuclearly targeted expression of PrxII in an activity-independent manner. Furthermore, the antioxidant butylated hydroxyanisole did not influence the etoposide-induced cell death. Mechanistically, the knockdown of Prx II expression impaired the DNA repair process by reducing the activation of the JNK/c-Jun pathway. These results suggest that PrxII is likely to be attributed to a tumor survival factor positively regulating JNK-dependent DNA repair with its inhibition possibly sensitizing cancer cells to chemotherapeutic agents.

Cancer remains a health problem worldwide; therefore, developing new therapies to increase the effectiveness of anticancer treatments is necessary. Two such methods are photodynamic therapy (PDT) and chemodynamic therapy (CDT). The intensive growth and increased metabolism of tumors lead to elevated levels of reactive oxygen species (ROS) within cancer cells. These cells develop several antioxidant mechanisms to protect them from this oxidative stress. Antioxidants also make tumors more resistant to chemotherapy and radiation. Glutathione (GSH) is an important and the most abundant endogenous cellular antioxidant. Photodynamic therapy and CDT are new methods that are based on the production of ROS,‑ therefore increasing oxidative stress in cancer cells. A significant problem with these therapies is the increased GSH levels, which is an adaptation of cancer cells to augmented metabolic processes. This paper presents various GSH depletion strategies that are used to improve PDT and CDT. While the main goal of GSH depletion in both PDT and CDT is to prevent its interaction with the ROS generated by these therapies, it should be remembered that the reduction of its level itself may initiate pathways leading to cancer cell death.

Emerging Designs of Aggregation-Induced Emission Agents for Enhanced Phototherapy Applications

Aggregation Turns BODIPY Fluorophores into Photosensitizers: Reversibly Switching Intersystem Crossing On and Off for Smart Photodynamic Therapy

Synergistic photodynamic and chemodynamic therapy using hypoxia-adaptive Ce6@Co nanoparticles for enhanced tumor suppression

Cancer cells contain more reactive oxygen species (ROS) than normal cells; therefore, ROS is closely related to tumorigenesis. While cancer cells control ROS levels through powerful antioxidant defense mechanisms, they are observed to remain higher than in normal cells. Often, cancer cells maintain an effective redox homeostasis by reprogramming metabolic machinery. Increased oxidative stress due to exogenous ROS generation therapy has been proposed to selectively kill cancer cells without affecting normal cells. During cancer treatment, it is well recognized that certain chemotherapy agents and radiation therapy can contribute to an accumulation of ROS. Recent studies have shown that the degree of oxidative damage will assess the mode of death of the cells. Free radicals, especially ROS, have been documented to be common mediators of apoptosis. It is believed that since cancer cell lines contain a subpopulation of cancer stem cells (CSCs), the anti-cancer activity of ROS would be even more pronounced, and thus, oxidative stress can be used as a possible tumor-containing CSC therapy technology. Photodynamic therapy (PDT) is one such technology. PDT is based on a cascade of synergistic effects between light, a photosensitizer (PS), and oxygen, which significantly facilitates regulation of the procedure. Therefore, anticancer drugs that kill malignant cells that induce the development of intracellular ROS, such as PDT, can be developed to treat cancer by targeting CSCs.KeywordsCancer metabolismCancer stem cellsPhotodynamic oxidative stressReactive oxygen species

The cancer genome contains many gene alterations. How cancer cells acquire these alterations is a matter for discussion. One hypothesis is that cancer cells obtain mutations in genome stability genes at an early stage of tumor development, which results in genetic instability and generates a gene pool that enhances cellular proliferation and survival. Another hypothesis puts its emphasis on the natural selection of gene mutations for fitness. Recent data for systematic cancer genome sequencing shows that mutations in stability genes are rare in human sporadic cancers. Instead, many “passenger” mutations that do not drive the carcinogenesis process have been found in the cancer genome. Both the hypotheses mentioned above fall short in explaining recent data. Recently, many studies demonstrate the role of the tumor microenvironment, especially hypoxia and reoxygenation, in genetic instability. In this review, literature will be presented which supports a third hypothesis, i.e. that hypoxia/re-oxygenation induces genetic instability.

A multifunctional nanosystem catalyzed by cascading natural glucose oxidase and Fe3O4 nanozymes for synergistic chemodynamic and photodynamic cancer therapy

Dual Reactive Oxygen Species Generator Independent of Light and Oxygen for Tumor Imaging and Catalytic Therapy

Reactive oxygen species-sensitive polymeric nanocarriers for synergistic cancer therapy

The concept and examples of type-III photosensitizers for cancer photodynamic therapy

Photodynamic therapy (PDT) and chemodynamic therapy (CDT) are both promising cancer treatments to inhibit tumor cells by generating highly cytotoxic reactive oxygen species (ROS). Herein, we report a novel tumor microenvironment (TME) stimulus-responsive water-soluble glycosylated photosensitizer (BT-TPE@Fe-Lac), which can serve as a high-efficiency antitumor agent by combining PDT and CDT, based on the coordination of Fe3+ with lactosyl bis(2-pyridylmethyl)amine and an AIE luminogen (benzothiazole-hydroxytetraphenylethene, BT-TPE). BT-TPE@Fe-Lac is stable under physiological conditions and selectively targets HepG2 cells via asialoglycoprotein receptor (ASGPR)-mediated endocytosis. It rapidly dissociates into AIE-active BT-TPE molecules and a lactosyl ferric(III) complex in the acidic lysosomes of cancer cells. Upon exposure to light, BT-TPE produces O2˙- radicals for type I PDT. The ferric(III) complex is reduced to an Fe(II) complex upon depletion of glutathione, which primes the breakdown of endogenous H2O2 within the tumor microenvironment, thus generating highly toxic ˙OH for enhanced CDT. Compared with the monotherapy of PDT or CDT, BT-TPE@Fe-Lac can significantly increase the intracellular ROS levels to induce more tumor cell death under low drug doses and hypoxia-dependent conditions. This strategy leverages the unique properties of the TME to optimize therapeutic outcomes, offering a promising approach for the TME-responsive nanoplatform in advanced cancer therapy.