Fe(II) and Tannic Acid-Cloaked MOF as Carrier of Artemisinin for Supply of Ferrous Ions to Enhance Treatment of Triple-Negative Breast Cancer

Abstract

Suppression of tumor development by inducing ferroptosis may provide a potential remedy for triple-negative breast cancer, which is sensitive to intracellular oxidative imbalance. Recently, artemisinin (ART) and its derivatives have been investigated as potential anticancer agents for the treatment of highly aggressive cancers via the induction of ferroptosis by iron-mediated cleavage of the endoperoxide bridge. Owing to its poor water solubility and limited intracellular iron content, it is challenging for further application in antitumor therapy. Herein, we developed ferrous-supply nano-carrier for ART based on tannic acid (TA) and ferrous ion (Fe(II)) coated on the zeolitic imidazolate framework-8 (ZIF) with ART encapsulated (TA-Fe/ART@ZIF) via coordination-driven self-assembly. Drug release experiments showed that ART was not nearly released in pH 7.4, while 59% ART was released in pH 5.0 after 10 h, demonstrating the excellent pH-triggered release. Meanwhile, a high level of intracellular ROS and MDA, accompanied with decreasing GSH and GPX4, displayed a newly developed nano-drug system displayed markedly enhanced ferroptosis. Compared with monotherapy, in vitro and vivo tumor inhibition experiments demonstrated higher efficiency of tumor suppression of TA-Fe/ART@ZIF. This work provides a novel approach to enhance the potency of ferroptotic nano-medicine and new directions for TBNC therapy.

Ferroptosis in cancer and cancer immunotherapy

“…This reminds us that the function of drugs may expand with more scientific exploration. It is worth mentioning that many nano-drugs have great potential in specifically inducing ferroptosis in tumor cells, and can be simply classified according to the nanomaterials and coating materials used (Table 4) [161][162][163][164][165][166][167][168][169][170][171][172][173][174][175][176][177][178]. However, not all nanomedicines are listed because they have fewer clinical applications compared with conventional drugs.…”

“…Increase ROS and SLC7A11 inhibition [167] FaPEG-MnMSN Mesoporous silica Sorafenib Promote Fenton reaction, SLC7A11 inhibition and GSH depletion [168] MoS2, WS2 Metal sulfide None GPX4 inhibition, Oxygen free radical generation, Lipid peroxidation [169] TA-Fe/ART@ZIF MOFs Artemisinin, Fe 2+ Promote Fenton reaction [170] RSL3@mPEG-PLys-AA Polymer RSL3 Promote Fenton reaction, GPX4 inhibition, Lipid peroxidation [171] SRF@Hb-Ce6 Protein Sorafenib GPX4 inhibition [172] LDL-DHA Self-assembled nanoparticles Omega-3 fatty acid, docosahexaenoic acid GSH depletion, GPX4…”

Artesunate Inhibits the Growth Behavior of Docetaxel-Resistant Prostate Cancer Cells

“…In good accordance with this, in both parental and DX-resistant DU145 cells significantly reduced GSH levels were apparent after exposure to ART, confirming ROS formation under ART administration. Similarly, ART increased ROS and decreased GSH in the most aggressive triple-negative breast cancer cells, resulting in intracellular oxidative imbalance and ferroptosis (61). Furthermore, ART induced ferroptosis in head and neck cancer cells by decreasing cellular GSH levels and increasing lipid ROS levels (28).…”

Design and development of nanostructured co delivery of artemisinin and chrysin for targeting hTERT gene expression in breast cancer cell line: possible clinical application in cancer treatment

“…It exerts its anti-cancer properties in various ways [16]. The level of iron are remarkably higher in cancerous cells than normal cells, and iron breaks down the endoperoxide structure in Artemisinin, leading to cell death [33]. Studies conducted by Guo-Qing Chen et al in 2019 demonstrated Art's antitumor property by direction breast TNCB cancer cells to ferroptosis, which is a type of cell death [34].…”