Local delivery of arsenic trioxide nanoparticles for hepatocellular carcinoma treatment

Hepatocellular carcinoma (HCC) is a malignancy with a poor prognosis. Surgery combined with chemotherapy has been recommended as a curative regimen for HCC. Nevertheless, the anticancer mechanisms of chemicals in hepatocellular carcinoma remain unclear. Pyroptosis is a type of programmed necrosis, and its mechanism in hepatocellular carcinoma is poorly understood. The efficacy and mechanism of arsenic trioxide nanoparticles in the treatment of HCC were explored in this research. Arsenic trioxide alone and arsenic trioxide nanoparticles were conveniently administered to mice intratumorally using a needle. Compared with As(2)O(3), As(2)O(3) nanoparticles (As(2)O(3)-NPs) showed better inhibition, promoted greater LDH release, and induced cell morphology indicative of pyroptosis in vitro. Compared with the free drug, As(2)O(3)-NPs increased GSDME-N expression and decreased Dnmt3a, Dnmt3b, and Dnmt1 expression in Huh7 cells. In vivo, As(2)O(3)-NPs induced a significant decrease in the expression of Dnmt3a, Dnmt3b and Dnmt1, but significantly upregulated the expression of GSDME-N (gasdermin E (GSDME) was originally found to be related to deafness; recently, it has been defined as a gasdermin family member associated with pyroptosis). As(2)O(3)-NPs inhibited tumor growth more strongly than As(2)O(3) or control, a finding likely attributed to the downregulation of PCNA and DNMT-related proteins and the upregulation of GSDME-N.