Synergic fabrication of arsenic and anticancer drug-loaded ZIF-8 nanocomposites for improved radiofrequency ablation of liver metastasis cancer therapy

Abstract

Clinical treatment of hepatocellular carcinoma (HCC) is notoriously tricky because radiofrequency ablation (RFA) might encourage metastasis of remaining HCC. The therapeutic efficacy of arsenic (A) and promising anticancer drug gemcitabine (G)-loaded zeolitic imidazolate framework-8 nanocomposites (AG@ZIF-8 NCs) on tumour remnants wasinvestigated. Results demonstrated that RFA significantly increased proliferation, induced metastasis, and triggered angiogenesis in recurrent tumours. We show that significant angiogenesis following RFA can increase the enhanced permeability and retention (EPR) effects and emphasize ZIF-8 carriers in recurrent tumours. e effectively fabricated biocompatible AG@ZIF-8 NCs. And they were superior to free gemcitabine in inhibiting cell proliferations, inducing apoptosis, blocking cell invasion and migration, and reversing in vitro EMT following sublethal heat treatment. In addition, AG@ZIF-8 NCs showed significantly improved therapeutic efficiency by reducing residual tumour development and in vivo metastasis compared to free gemcitabine. This study establishes a new standard for managing HCC that persists after RFA.