Bismuth-based mesoporous nanoball carrying sorafenib for synergistic photothermal and molecularly-targeted therapy in an orthotopic hepatocellular carcinoma xenograft mouse model

Colloids Surf B Biointerfaces. 2025 Jan:245:114279. doi: 10.1016/j.colsurfb.2024.114279. Epub 2024 Oct 1.

Abstract

Sorafenib (SOR), a multi-kinase inhibitor for advanced hepatocellular carcinoma (HCC), has limited clinical application due to severe side effects and drug resistance. To overcome these challenges, we developed a bismuth-based nanomaterial (BOS) for thermal injury-assisted continuous targeted therapy in HCC. Initially, the mesoporous nanomaterial was loaded with SOR, forming the BOS@SOR nano-carrier system for drug delivery and controlled release. Notably, compared to targeted or photothermal therapy alone, the combination therapy using this nano-carrier system significantly impaired cell proliferation and increased apoptosis. In vivo efficacy evaluations demonstrated that BOS@SOR exhibited excellent biocompatibility, confirmed through hemolysis and biochemical analyses. Additionally, BOS@SOR enhanced contrast in computed tomography, aiding in the precise identification of HCC size and location. The photothermal therapeutic properties of bismuth further contributed to the synergistic anti-tumor activity of BOS@SOR, significantly reducing tumor growth in an orthotopic xenograft HCC model. Taken together, encapsulating SOR within a bismuth-based mesoporous nanomaterial creates a multifunctional and environmentally stable nanocomposite (BOS@SOR), enhancing the therapeutic effect of SOR and presenting an effective strategy for HCC treatment.

Keywords: Bismuth; Hepatocellular carcinoma; Molecularly-targeted therapy; Photothermal therapy; Sorafenib.

MeSH terms

  • Animals
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Apoptosis / drug effects
  • Bismuth* / chemistry
  • Bismuth* / pharmacology
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / pathology
  • Carcinoma, Hepatocellular* / therapy
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / pathology
  • Liver Neoplasms* / therapy
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Targeted Therapy
  • Particle Size
  • Photothermal Therapy*
  • Porosity
  • Sorafenib* / chemistry
  • Sorafenib* / pharmacology
  • Surface Properties
  • Xenograft Model Antitumor Assays

Substances

  • Sorafenib
  • Bismuth
  • Antineoplastic Agents