Doxorubicin-Loaded UiO-66/Bi₂S₃ Nanocomposite-Enhanced Synergistic Transarterial Chemoembolization and Photothermal Therapy against Hepatocellular Carcinoma

Transcatheter arterial chemoembolization (TACE) is the first choice for patients with intermediate hepatocellular carcinoma (HCC), but clinical applications still face some problems, such as the difficulties in clearing all cancer cells and lack of targeting, which would damage normal liver cells. Recently, photothermal therapy (PTT) and nanodelivery systems have been used to improve the efficacy of TACE. However, most of these strategies achieve only a single function, and the synthesis process is complicated. Here, a simple one-step solvothermal method was used to develop multifunctional nanoparticles (UiO-66/Bi₂S₃@DOX), which can simultaneously achieve photothermal effects and low pH-triggered DOX release. UiO-66/Bi₂S₃ exhibited a pH-responsive release behavior and an excellent photothermal effect in a series of in vitro and in vivo studies. Biocompatibility was confirmed by cytotoxicity and hemocompatibility evaluations. The rat N1S1 liver tumor model was established to investigate the therapeutic effect and biosafety of the nanoplatforms using TACE. The results revealed that the combination of TACE and PTT resulted in remarkable tumor growth inhibition, and the histopathological assay further revealed extensive necrosis, downregulated angiogenesis, increased apoptosis, and proliferation in the tumor response. These results demonstrated that this nanosystem platform was a promising therapeutic agent for enhancing TACE therapy for HCC treatment.