Nanoscale CaO2 materials for synergistic transarterial chemoembolization in a VX2 orthotopic rabbit liver cancer model

Transcatheter arterial chemoembolization (TACE) is extensively used in the treatment of hepatocellular carcinoma (HCC), but its efficacy is usually limited to secondary tumor hypoxia and other progressive exacerbation of the abnormal tumor microenvironment (TME). Herein, we synthesized polyvinyl pyrroli-done (PVP)-coated CaO2 nanoparticles (CaO2 NPs) and applied them as a synergistic agent to improve the antitumor efficacy of TACE. After injection into the tumor, CaO2 NPs reacted with water to generate abundant oxygen, hydroxyl ions (OH -), and calcium ions (Ca2+), thereby relieving tumor hypoxia, neutral-izing acid, and overloading Ca2+ to mediate antitumor effects. Moreover, the effect of chemotherapeutic drugs within the TACE was improved due to the modulated TME. CaO2 NPs efficiently regulated the TME and improved the antitumor effect of doxorubicin under hypoxia conditions in vitro . Compared to other groups, the TACE + CaO2 NPs group achieved the lowest tumor growth rate, highest tumor necrosis rate, lowest expression of histological markers associated with hypoxia and angiogenesis (HIF-alpha, VEGF, and CD31), and highest CD8+ T cell recruitment in vivo . Thus, these findings demonstrated that CaO2 NPs provide synergy for TACE therapy in the VX2 orthotopic rabbit liver cancer model, suggesting that they have a potential broad clinical application.Statement of significanceThe efficacy of transcatheter arterial chemoembolization (TACE) for treatment of hepatocellular carcinoma is usually limited to secondary tumor hypoxia and other progressive exacerbation of the abnormal tumor microenvironment (TME). To address this issue, we synthesized CaO2 nanoparticles (CaO2 NPS) which would react with water to generate abundant oxygen, hydroxyl ions (OH -), and calcium ions (Ca2+), thereby relieving tumor hypoxia, neutralizing the acidic TME, and inducing Ca2+ overloading. The effi-cacy of CaO2 NPs in combination with TACE was investigated in an orthotopic rabbit liver cancer model, and the results showed the great synergetic antitumor effect of TACE and CaO2 NPs.(c) 2022 The Authors. Published by Elsevier Ltd on behalf of Acta Materialia Inc. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

Automated summary

Transcatheter arterial chemoembolization (TACE) is commonly used for hepatocellular carcinoma (HCC) treatment, but its efficacy is limited by tumor hypoxia and the abnormal tumor microenvironment (TME). In this study, CaO2 nanoparticles were synthesized and combined with TACE to enhance the antitumor effect. CaO2 NPs relieved tumor hypoxia, neutralized the acidic TME, and induced Ca2+ overloading, resulting in improved efficacy of TACE in the rabbit liver cancer model.