Enhanced antitumor efficacy and safety of cannabidiol-loaded O-carboxymethyl chitosan nanomicelles in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) remains a major global health challenge, and effective drug delivery strategies are still needed to improve therapeutic outcomes. In this study, cannabidiol-loaded O-carboxymethyl chitosan (CBD/CCMC) nanomicelles were evaluated for their biodistribution, antitumor efficacy, and in vivo biosafety in H22 tumor-bearing mice. The results showed that CBD/CCMC nanomicelles exhibited prolonged retention in vivo and enhanced accumulation in tumor tissues, as demonstrated by in vivo fluorescence imaging. Compared with free CBD, the nanomicelle formulation significantly inhibited tumor growth, with a tumor inhibition rate of 53.57% versus 17.04%. In addition, CBD/CCMC nanomicelles effectively maintained body weight and reduced systemic toxicity. Histopathological analysis revealed increased tumor cell apoptosis and necrosis in the treatment group. Furthermore, elevated levels of IL-2 and TNF-α were observed, suggesting a potential modulation of tumor-associated immune responses. Overall, these findings indicate that CCMC-based micelles can enhance tumor accumulation and antitumor activity of CBD while maintaining favorable biosafety, providing a promising delivery strategy for hepatocellular carcinoma treatment.