Acid‐Responsive H₂‐Releasing 2D MgB₂ Nanosheet for Therapeutic Synergy and Side Effect Attenuation of Gastric Cancer Chemotherapy

Abstract

The hydrogen molecule is recognized as a high potential to attenuate toxic side effects of chemotherapy and also enhance chemotherapeutic efficacy, and the development of a novel hydrogen‐generating prodrug for facile, safe, and efficient hydrogen delivery is vitally important for combined hydrogenochemotherapy but is still challenging. Here, targeting gastric cancer, a 2D magnesium boride nanosheet (MBN) is synthesized as a new type of acid‐responsive hydrogen‐releasing prodrug by an ultrasound‐assisted chemical etching route, which is used to realize hydrogenochemotherapy by combination of facile oral administration of polyvinylpyrrolidone (PVP)‐encapsulating MBN (MBN@PVP) pills with routine intravenous injection of doxorubicin (DOX). The MBN@PVP pill has high stability in normal tissues/blood environments as well as high gastric acid‐responsiveness with sustained release behavior, which matches well with its metabolism rate in the stomach in great favor of continuous and long‐term hydrogen administration. Hydrogenochemotherapy with DOX+MBN@PVP has remarkably prolonged the survival time of gastric tumor‐bearing mice by reducing the toxic side effects of chemotherapy. The mechanism for therapeutic synergy and side effect attenuation of hydrogenochemotherapy is discovered to be derived from the selectivity of hydrogen molecules in inhibiting aerobic respiration of gastric cells but activating aerobic respiration of normal cells including marrow mesenchymal stem cells and cardiac, hepatic, and splenic cells.

Photocatalysis-mediated drug-free sustainable cancer therapy using nanocatalyst

“…It has well proved that the main target of hydrogen molecule is mitochondrion and thus hydrogen gas can induce cancer apoptosis by adjusting cellular energy metabolism through mitochondria 32,33 , while GSH depletion can do damage to the ADS of cancer because intratumoral over-expressed GSH has high reduction capability and play an essential role in maintaining intratumoral redox balance [34][35][36][37][38] . Therefore, we investigated the effect of the SnS 1.68 -WO 2.41 nanocatalyst on both intracellular levels of ATP and ROS and the functions of mitochondria and DNA in the presence and absence of NIR irradiation in order to uncover the mechanism of hole/hydrogen therapy.…”

Microfactories for Intracellular Locally Generated Hydrogen Therapy: Advanced Materials, Challenges, and Opportunities

“…The reactions were recently explored for H 2 therapy. As shown in Figure a–b, 2D magnesium boride nanosheet (MBN) was synthesized by an ultrasound‐assisted etching rout . The high aqueous stability and acid responsiveness of MBN lead to local and sustained release of H 2 in acidic gastric microenvironment (Figure c).…”

“…Doxorubicin (DOX) is a chemotherapy medication to treat cancer with serious side effects. The MBN@PVP pills could generate H 2 through oral uptake in stomach continuously . BGC‐823 tumour‐bearing mice model has been created to assess the combined effect of DOX and MBN@PVP in gastric cancer therapy.…”

Investigation of Anti-proliferative and Anti-migratory Properties of Recombinant J2-C2 Against Tumor Cells

“…Chemotherapy is one of the most effective methods for cancer treatment. Toxic side effects of chemotherapy and acquired chemotherapy resistance are still important problems to be solved (Cheok, 2012;Fan et. al., 2019).…”