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Podophyllotoxin has been explored as an anticancer, antiviral, and antibacterial agent; however, its low water solubility and toxicity limit its use. In this study, the efficacy of a more soluble and less toxic polyamidoamine (PAMAM) dendrimer-conjugated podophyllotoxin (DPODO) was evaluated against chemically induced hepatocellular carcinoma (HCC) in mice. HCC was induced by giving 0.01% diethylnitrosamine (DENA) in drinking water for 16 weeks. The HCC-induced mice were treated with 10 or 20 mg per kg body weight DPODO. The DENA administration led to HCC development, characterized by anisocytosis, karyomegaly, inflammation and degenerative changes in the liver. The DPODO treatment at 10 mg and 20 mg doses significantly reduced the histopathological changes in liver tissue. The DPODO treatment also significantly lowered the levels of inflammatory markers IL-6 and NF-κB in serum …