Cyclodextrin‐Derived ROS‐Generating Nanomedicine with pH‐Modulated Degradability to Enhance Tumor Ferroptosis Therapy and Chemotherapy

Abstract

Nowadays, destruction of redox homeostasis to induce cancer cell death is an emerging anti‐cancer strategy. Here, the authors utilized pH‐sensitive acetalated β‐cyclodextrin (Ac‐β‐CD) to efficiently deliver dihydroartemisinin (DHA) for tumor ferroptosis therapy and chemodynamic therapy in a synergistic manner. The Ac‐β‐CD‐DHA based nanoparticles are coated by an iron‐containing polyphenol network. In response to the tumor microenvironment, Fe2+/Fe3+ can consume glutathione (GSH) and trigger the Fenton reaction in the presence of hydrogen peroxide (H2O2), leading to the generation of lethal reactive oxygen species (ROS). Meanwhile, the OO bridge bonds of DHA are also disintegrated to enable ferroptosis of cancer cells. Their results demonstrate that these nanoparticles acted as a ROS generator to break the redox balance of cancer cells, showing an effective anticancer efficacy, which is different from traditional approaches.

Mesoporous polydopamine nanoplatforms loaded with calcium ascorbate for amplified oxidation and photothermal combination cancer therapy

“…Due to the limitations of conventional cancer-treatment methods used in clinical practice (e.g., surgery, chemotherapy, and radiotherapy), it is still necessary to continuously develop new treatment strategies to effectively ght against cancer [35]. In this study, we successfully prepared a biocompatible and versatile nanoplatform based on MpDA nanoparticles and a phase-change material for delivering Vc-Ca, simultaneously enabling combination therapy of hyperthermia, ROS generation, and suppression of tumor antioxidant capability.…”

“…•− , which play vital roles in regulating various physiological functions of living organisms [7,8]. The moderate ROS level can elicit cell proliferation and differentiation, once ROS concentrations beyond a certain threshold value will damage DNA, proteins, and lipids of cells, leading to cell damages or even death [9,10]. Although cancer cells can evade oxidative damage by relying on the endogenous antioxidant system, they produce increased sensitivity for the further reinforced exogenous oxidative stress [2,11,12].…”

Highly Penetrable Drug-Loaded Nanomotors for Photothermal-Enhanced Ferroptosis Treatment of Tumor

“…JC-1 probes are commonly used to stain cells to measure mitochondrial membrane potential. 5,20,37 MCF-7 cells were seeded and cultured in confocal dishes overnight and incubated with (I) PBS, (II) PHPF (200 μg/mL), and (III) PHPF+NIR (200 μg/mL). After 4 h of culture, the cells were incubated with JC-1 (1 μg/mL) for 30 min at 37 °C.…”

“…The accumulation of iron ions in cells may lead to cell death, which is characterized by iron-dependent lipid peroxidation. This is a kind of programmed cell death induced by the production of iron-dependent reactive oxygen species (ROS), which is defined as ferroptosis and has attracted extensive attention. − The mechanism of ferroptosis is closely related to the inactivation of glutathione peroxidase 4 (GPX4) and the production and accumulation of ROS by the Fenton/Fenton-like reaction, which ultimately leads to the accumulation of lipid peroxide (LPO). , Recently, many studies have involved the use of the Fenton/Fenton-like reaction to combine Fe-, Co-, Mn-, and Cu-based inorganic nanocatalysts with hydrogen peroxide (H 2 O 2 ) overexpressed in a tumor microenvironment (TME) to produce cytotoxic •OH, thus effectively inducing ferroptosis to treat tumor. , It can also inhibit the activity of GPX4 (the only enzyme in cell that can be used for the reduction of liposome peroxide) by consuming intracellular glutathione (GSH), so as to induce ferroptosis for tumor treatment. , …”

A Stepwise-Confined Self-Reduction Strategy to Construct a Dynamic Nanocatalyst for Boosting Tumor Catalytic Therapy

“…Similarly, the low-valence Cu + exerted synergistic effects, promoted Fe 3+ to Fe 2+ , and thus activated H 2 O 2 to generate •OH . A self-enhanced formulation for cancer treatment by utilizing CuS (Cu + ) to boost the reduction process of Fe 3+ to Fe 2+ has been proposed by Nie et al Additionally, the mildly acidic environment, the overexpressed H 2 O 2 , and the excess glutathione (GSH) in tumor cells have been the focus of improved tumor therapies based on high levels of intracellular GSH to expedite the reaction of Fe 3+ to Fe 2+ for the highly toxic •OH generation. − However, most current Fenton catalysts still suffer from a complex and tedious preparation process and low catalytic efficiency in tumor sites. Thus, developing a facile but simple strategy to directly deliver highly active and low-valence metal species through a precise preparation of bioapplicable Fenton catalysts for tumor therapy remains a great challenge.…”