Bismuth-Based Mesoporous Nanoball Carrying Sorafenib for Synergistic Photothermal and Molecularly-Targeted Therapy in an Orthotopic Hepatocellular Carcinoma Xenograft Mouse Model

Abstract

AbstractBackground Sorafenib (SOR), a multi-kinase inhibitor for advanced hepatocellular carcinoma (HCC), has limited clinical application due to severe side effects and evident drug resistance. To overcome these challenges, a bismuth-based nanomaterial (BOS) is herein developed to achieve thermal injury-assisted continuous targeted therapy in HCC. Results Initially, the mesoporous nanomaterial was loaded with SOR to form BOS@SOR nano-carrier system for SOR delivery and controlled release. Notably, compared with targeted or photothermal therapy alone, the combinational therapy of the nano-carrier system displayed impaired cellular proliferation and increased propensity toward apoptosis. After evaluating thein vivoefficacy, BOS@SOR was subjected to hemolysis and biochemistry analysis, exhibiting excellent biocompatibility. Meanwhile, BOS@SOR could indicate the size and location of HCCviathe more excellent computed tomography contrast enhancement. Combined with the photothermal therapy ability of bismuth, BOS@SOR exhibited synergistic anti-tumor activity and markedly reduced tumor growth in an orthotopic xenograft HCC model. Conclusions Taken together, the bismuth-based nano-theranostic platform could improve the therapeutic effect of SOR and serve as an effective strategy for HCC treatment.