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<p>Hepatocellular carcinoma (HCC) remains a critical global health burden, and advanced drug delivery strategies are urgently required to improve cancer therapeutic outcomes. In this work, cannabidiol-loaded O-carboxymethyl chitosan-g-cholesterol succinic acid monoester (CBD/CCMC) nanomicelles were systematically investigated for their <i>in vivo</i> biodistribution, anti-tumor efficacy and biosafety using H22 tumor-bearing mice. <i>In vivo</i> fluorescence imaging verified that CBD/CCMC nanomicelles possessed prolonged <i>in vivo</i> circulation and superior tumor-targeted accumulation. Compared with free CBD, the nanomicelles group exerted a stronger tumor suppression effect, with a tumor inhibition rate of 53.57%, which was markedly higher than the 17.04% of free CBD. Moreover, CBD/CCMC nanomicelles effectively alleviated systemic toxicity and prevented body weight loss in tumor-bearing mice. Histopathological examination confirmed obvious apoptosis and necrosis of tumor cells after nanomicelles treatment. Meanwhile, the upregulated expression of IL-2 and TNF-α indicated that the prepared nanomicelles could regulate tumor-related immune responses. Collectively, CCMC-based nanomicelles can greatly enhance the tumor enrichment and anti-tumor performance of CBD with satisfactory biocompatibility. This study offers a promising delivery platform for the targeted treatment of hepatocellular carcinoma.</p>

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Enhanced Anti-Tumor Efficacy and Safety of Cannabidiol-Loaded O-Carboxymethyl Chitosan Nanomicelles in Hepatocellular Carcinoma

  • 期刊论文

  • 发表日期：

    2026年5月26日

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  • Wenhui Ruan,
  • Yanlin Kang,
  • Zhijuan Wu,
  • Zhihao Chen,
  • Rui Li

摘要

Hepatocellular carcinoma (HCC) remains a critical global health burden, and advanced drug delivery strategies are urgently required to improve cancer therapeutic outcomes. In this work, cannabidiol-loaded O-carboxymethyl chitosan-g-cholesterol succinic acid monoester (CBD/CCMC) nanomicelles were systematically investigated for their in vivo biodistribution, anti-tumor efficacy and biosafety using H22 tumor-bearing mice. In vivo fluorescence imaging verified that CBD/CCMC nanomicelles possessed prolonged in vivo circulation and superior tumor-targeted accumulation. Compared with free CBD, the nanomicelles group exerted a stronger tumor suppression effect, with a tumor inhibition rate of 53.57%, which was markedly higher than the 17.04% of free CBD. Moreover, CBD/CCMC nanomicelles effectively alleviated systemic toxicity and prevented body weight loss in tumor-bearing mice. Histopathological examination confirmed obvious apoptosis and necrosis of tumor cells after nanomicelles treatment. Meanwhile, the upregulated expression of IL-2 and TNF-α indicated that the prepared nanomicelles could regulate tumor-related immune responses. Collectively, CCMC-based nanomicelles can greatly enhance the tumor enrichment and anti-tumor performance of CBD with satisfactory biocompatibility. This study offers a promising delivery platform for the targeted treatment of hepatocellular carcinoma.