Nano-revolution in hepatocellular carcinoma: A multidisciplinary odyssey - Are we there yet?

Abstract

In this editorial we comment on the review by Zhou et al reviewing the landscape of nanomedicine in the treatment of hepatocellular carcinoma (HCC). We focus on the immense potential of nanotechnology, particularly ligand-receptor mediated nanotherapy, in revolutionizing the treatment landscape of HCC. Despite advancements in multidisciplinary treatment, HCC remains a significant global health challenge. Ligand-mediated nanotherapy offers the opportunity for precise drug delivery to tumor sites, targeting specific receptors overexpressed in HCC cells, thereby enhancing efficacy and minimizing side effects. Overcoming drug resistance and aggressive tumor biology is facilitated by nanomedicine, bypassing traditional hurdles encountered in chemotherapy. Examples include targeting glypican-3, asialoglycoprotein, transferrin receptor or folic acid receptors, capitalizing on their over-expression in tumor cells. The ability for multi-receptor targeting through dual-ligand nanoparticle modification holds the prospect of further enhancement in specificity and efficacy of directed therapy. However, challenges including immune responses, reproducibility in nanoparticle synthesis, and production scalability remain. Future directions involve refining targeting strategies, improving drug release mechanisms, and streamlining production processes to enable personalized and multifunctional nanotherapies. Overall, the integration of nanotherapy in HCC treatment holds immense promise, but continued partnership and effort are needed in offering hope for more effective, precise, and accessible clinical care in the management of HCC.

Keywords: Hepatocellular carcinoma; Ligand-receptor mediated nanotherapy; Nanomedicine; Personalized medicine; Precision medicine; Targeting.

Figure 1

Application of nanomedicine in hepatocellular carcinoma. The tumor microenvironment in hepatocellular carcinoma and over-expressed receptors on tumor cells including anti-glypican-3, asialoglycoprotein, transferrin receptor, folic acid receptor, Axl and integrins. These receptors on tumor cells are prime targets of nanontherapy, such as sorafenib loaded polymer-based nanoparticles[8-13,16]. GPC3: Anti-glypican-3; FAR: Folic acid receptor; TfR: Transferrin receptor; ASGPR: Asialoglycoprotein.