Dihydroartemisinin-Loaded Magnetic Nanoparticles for Enhanced Chemodynamic Therapy

Abstract

Recently, chemodynamic therapy (CDT) has represented a new approach for cancer treatment with low toxicity and side effects. Nonetheless, it has been a challenge to improve the therapeutic effect through increasing the amount of reactive oxygen species (ROS). Herein, we increased the amount of ROS agents in the Fenton-like reaction by loading dihydroartemisinin (DHA) which was an artemisinin (ART) derivative containing peroxide groups, into magnetic nanoparticles (MNP), thereby improving the therapeutic effect of CDT. Blank MNP were almost non-cytotoxic, whereas three MNP loading ART-based drugs, MNP-ART, MNP-DHA, and MNP-artesunate (MNP-AS), all showed significant killing effect on breast cancer cells (MCF-7 cells), in which MNP-DHA were the most potent. What's more, the MNP-DHA showed high toxicity to drug-resistant breast cancer cells (MCF-7/ADR cells), demonstrating its ability to overcome multidrug resistance (MDR). The study revealed that MNP could produce ferrous ions under the acidic condition of tumor microenvironment, which catalyzed DHA to produce large amounts of ROS, leading to cell death. Further experiments also showed that the MNP-DHA had significant inhibitory effect on another two aggressive breast cancer cell lines (MDA-MB-231 and MDA-MB-453 cells), which indicated that the great potential of MNP-DHA for the treatment of intractable breast cancers.

Osthole Inhibits Breast Cancer Progression through Upregulating Tumor Suppressor GNG7

“…In the past few decades, more and more traditional Chinese medicines have been found to have anti-inflammatory and tumor suppression capabilities, which may open up new prospects for the treatment of malignant tumors [ 4 , 5 ]. Osthole (OST, C 15 H 16 O 3 , molecular weight: 244.280 g/mol, Figures 1(a) – 1(b) ) is a plant-derived compound that can inhibit the proliferation of malignant cells and has an effective anticancer effect in multiple types of cancers [ 6 ].…”

External and Internal Stimuli-Responsive Metallic Nanotherapeutics for Enhanced Anticancer Therapy

“…The amount of endogenous H 2 O 2 is insufficient for the Fenton reaction to generate an adequate amount of ROS to eradicate cancer cells. Shengdi et al reported that artemisinin (ART) and its derivative, which contains a peroxy group accelerating the Fenton reaction with iron or copper ions, were loaded into MNPs to enhance the cytotoxic effect (Guo et al, 2020a ). MNPs are degraded in acidic tumor conditions to release Fe 2+ ions that induce the Fenton reaction.…”

“…MNPs are degraded in acidic tumor conditions to release Fe 2+ ions that induce the Fenton reaction. Under acidic conditions (pH 5.0), the iron content is 10.45 μg/mL, 10 times higher than that in the normal physiological condition of 1.61 μg/mL (Guo et al, 2020a ). MNP degradation accelerates the release of ART and its derivatives, generating significant additional peroxidase to enhance the Fenton reaction inside cells.…”

Repositioning of Antiparasitic Drugs for Tumor Treatment

“…Further, excessive amounts of ROS may trigger an ER stress response in cancer cells ( 99 ), but the specific mechanism is not clear. Interestingly, increasing the concentration of ferrous ions and oxygen in the tumor environment to further increase the concentration of ROS has been shown to enhance the anticancer activity of ARTs ( 101 , 102 ), which provides a possible strategy for the development of new anticancer drugs based on ARTs.…”