Therapeutic and Preventive Potential of Novel Sulfur Nanoparticles Via Immunomodulation in Hepatocellular Carcinoma

Abstract Background Hepatocellular carcinoma (HCC) has one of the highest mortality rates among solid cancers and remains a major global health burden. Its incidence has been rising over the past 20 years and is projected to continue increasing in the coming decades. Current global models predict that the burden of liver cancer, including HCC, may nearly double by 2050 if present trends continue, driven by viral hepatitis, metabolic dysfunction-associated steatotic liver disease, and alcohol-related liver disease. Despite advances in diagnosis and therapy, outcomes remain poor due to late detection and limited effective treatment options. Methods This study was designed in three arms, the first was to evaluate the safety of sulfur extract nanoparticles (SEx-NP) on the liver, and then the second was studying the ability of SEx-NP to prohibit the occurrence of HCC, while the third was evaluating the therapeutic effect of SEx-NP on HCC. Results Acute toxicity study was done using 1800 mg/kg of SEx-NP which was the maximum soluble dose, it was safe. Sub-chronic toxicity study proved that 180 mg/kg of SEx-NP was safe. Preventive and therapeutic efficacy studies were done, animal groups were: Negative control, positive control received diethyl-nitrosamine (DENA) (200 mg/kg), and carbon tetrachloride (CCL 4 ) 9% (0.5 ml/kg) intraperitoneally, to induce a rat model of HCC, preventive groups were given SEx-NP orally (90 and 180 mg/kg), together with DENA and CCL 4 for 3 and 6 months, therapeutic group was given SEx-NP orally (90 mg/kg) for 1 month, after induction of HCC. Biochemical parameters measured in sera were: GPT, GOT, MDA, IL-β 6 , TNF-α, α-fetoprotein, ova albumin, TGF-β 1 and pyruvate kinase levels in addition to histopathologic and immuno-histochemical examination of hepatic tissues. SEx-NP reduced GPT, GOT, MDA, IL-β 6 , TNF-α, α-fetoprotein, ova albumin, TGF-β 1 and pyruvate kinase with better effect in the therapeutic study, it also improved the hepatic histopathologic pictures. Conclusions Our results demonstrate the potential inhibitory effect of SEx-NP tumor on growth during early HCC stages, reinforcing its prophylactic promise in liver cancer prevention and liver health support. Finally, we can conclude that SEx-NP is a promising anti-neoplastic supplement.