Periodic mesoporous organosilica-coated magnetite nanoparticles combined with lipiodol for transcatheter arterial chemoembolization to inhibit the progression of liver cancer

Transcatheter arterial chemoembolization (TACE) is standard locoregional therapy for hepatocellular carcinoma (HCC) that involves the injection of chemotherapeutic drugs with embolic agents into tumor tissues through intra-arterial transcatheter infusion. TACE technology using lipiodol emulsion has been most widely used in the treatment of human HCC. However, lipiodol emulsions with anticancer drugs do not stably maintain high drug concentrations at tumor sites. Herein, we developed a dual-modality imaging nanoplatform for the TACE treatment of liver cancer by integrating periodic mesoporous organosilica (PMO) with magnetite (Fe3O4) nanoparticles and Cy5.5 molecules (denoted as Fe3O4@PMO-Cy5.5). Fe3O4@PMO-Cy5.5 showed an excellent doxorubicin (Dox)-loading capacity, sensitive drug release behavior under acidic conditions, and good biocompatibility. Moreover, Cy5.5-mediated optical imaging showed that Dox-loaded Fe3O4@PMO-Cy5.5 (Fe3O4@PMO-Cy5.5-Dox) could enter liver cancer cells and effectively inhibit their growth. In addition, Fe3O4@PMO-Cy5.5-Dox was used in combination with transarterial embolization for the treatment of in situ VX2 liver tumors in rabbits. Magnetic resonance imaging (MRI) evaluation showed that Fe3O4@PMO-Cy5.5-Dox perfused through arteries was deposited into liver tumors, and Fe3O4@PMO-Cy5.5-Dox combined with lipiodol to control liver tumors yielded the optimal therapeutic effect. In addition, histological analysis showed that compared with both lipiodol embolization and traditional lipiodol combined with Dox chemoembolization, Fe3O4@PMO-Cy5.5-Dox combined with lipiodol chemoembolization induced more complete tumor tissue necrosis. In summary, these results indicate that the Fe3O4@PMO-Cy5.5-Dox platform has the potential to become an advanced tool for the transarterial treatment of unresectable liver cancer.