Homogenous multifunctional microspheres induce ferroptosis to promote the anti-hepatocarcinoma effect of chemoembolization

Abstract

Transcatheter arterial chemoembolization (TACE) is one of the main palliative therapies for advanced hepatocellular carcinoma (HCC), which is also regarded as a promising therapeutic strategy for cancer treatment. However, drug-loaded microspheres (DLMs), as commonly used clinical chemoembolization drugs, still have the problems of uneven particle size and unstable therapeutic efficacy. Herein, gelatin was used as the wall material of the microspheres, and homogenous gelatin microspheres co-loaded with adriamycin and Fe3O4 nanoparticles (ADM/Fe3O4-MS) were further prepared by a high-voltage electrospray technology. The introduction of Fe3O4 nanoparticles into DLMs not only provided excellent T2-weighted magnetic resonance imaging (MRI) properties, but also improved the anti-tumor effectiveness under microwave-induced hyperthermia. The results showed that ADM/Fe3O4-MS plus microwave irradiation had significantly better antitumor efficacy than the other types of microspheres at both cell and animal levels. Our study further confirmed that ferroptosis was involved in the anti-tumor process of ADM/Fe3O4-MS plus microwave irradiation, and ferroptosis marker GPX4 was significantly decreased and ACSL4 was significantly increased, and ferroptosis inhibitors could reverse the tumor cell killing effect caused by ADM/Fe3O4-MS to a certain extent. Our results confirmed that microwave mediated hyperthermia could amplify the antitumor efficacy of ADM/Fe3O4-MS by activating ferroptosis and the introduction of Fe3O4 nanoparticles can significantly improve TACE for HCC. This study confirmed that it was feasible to use uniform-sized gelatin microspheres co-loaded with Fe3O4 nanoparticles and adriamycin to enhance the efficacy of TACE for HCC. Graphical Abstract

Multifunctional nanoparticle for cancer therapy

“… 165 , 166 For example, Chen et al. 167 prepared gelatin microspheres dual‐loaded adriamycin (ADM) and Fe 3 O 4 nanoparticles (ADM/Fe 3 O 4 MS), in which the ADM/Fe 3 O 4 MS were obtained using gelatin, ADM hydrochloride, and Fe 3 O 4 nanoparticles via the high‐voltage electrospray method. The introduction of SPIONs based on Fe 3 O 4 enabled microspheres to possess the ability to induce hyperthermia and excellent T 2 ‐weighted MRI properties.…”

Smart nanoparticles and microbeads for interventional embolization therapy of liver cancer: state of the art

“…Superparamagnetic iron oxide nanoparticles (SPIONs), which function as microwave-sensitive material, absorb microwave energy through unpaired electrons (Fe 2+ , Fe 3+ ). When these excited electrons return to the ground state, they release phonons that allow for the conversion of microwave energy into heat energy [ 49 ]. In a microwave field, SPIONs in microspheres can rapidly increase a high temperature to kill tumors and further induce ferroptosis of tumor cells.…”

Biosensors and Drug Delivery in Oncotheranostics Using Inorganic Synthetic and Biogenic Magnetic Nanoparticles

“…To reduce toxicity and increase biocompatibility, magnetic nanoparticles can be coated with proteins. Chen et al used high-voltage electrospray technology to develop microspheres based on Fe 3 O 4 nanoparticles with a gelatin shell for loading them with adriamycin [ 96 ]. In addition to a good antitumor efficacy, the obtained nanocomplex activated ferroptosis in tumor cells (the ferroptosis marker GPX4 was significantly decreased, and ACSL4 was significantly increased) together with exposure to microwave hyperthermia, and also showed excellent properties for magnetic resonance imaging.…”