Abstract

Liver cancer is one of the most common causes of cancer mortality worldwide. Chemotherapy and radiotherapy are the conventional therapies generally employed in patients with liver tumors. The major issue associated with the administration of chemotherapeutics is their high toxicity and lack of selectivity, leading to systemic toxicity that can be detrimental to the patient’s quality of life. An important approach to the development of original liver-targeted therapeutic products takes advantage of the employment of biologically active ligands able to bind specific receptors on the cytoplasmatic membranes of liver cells. In this perspective, glycyrrhetinic acid (GA), a pentacyclic triterpenoid present in roots and rhizomes of licorice, has been used as a ligand for targeting the liver due to the expression of GA receptors on the sinusoidal surface of mammalian hepatocytes, so it may be employed to modify drug delivery systems (DDSs) and obtain better liver or hepatocyte drug uptake and efficacy. In the current review, we focus on the most recent and interesting research advances in the development of GA-based hybrid compounds and DDSs developed for potential employment as efficacious therapeutic options for the treatment of hepatic cancer.

Highlights

  • Liver cancer is one of the most common cancers and among the most common causes of cancer mortality worldwide [1]

  • This approach was examined by Jiang and coworkers [53], who evaluated glycyrrhetinic acid (GA)-modified PEGylated liposomes in order to increase active targeting to hepatocellular carcinoma (HCC) cells and tissue of CUR and combretastatin A4 phosphate (CA4P)

  • Chemotherapy is the main treatment for hepatic tumors, including HCC, but it is still challenging due to several problems, including its nonselective biodistribution and effects, as well as multidrug chemoresistance

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Summary

Introduction

Liver cancer is one of the most common cancers and among the most common causes of cancer mortality worldwide [1]. An enormously important approach to the development of original therapeutic products actively targeting liver cancer takes advantage of the employment of biologically active ligands able to bind specific receptors on cytoplasmatic membranes of liver cells. These ligands may be used to synthesize hybrid compounds based on traditional chemotherapy drugs or to functionalize the surface of micro- and nano-drug delivery systems (DDSs) since they can allow a specific and efficient drug internalization into tumoral cells [7]. Since DDSs accumulated into tumor interstitial fluid may be internalized into tumor cells due to specific cell surface interactions, receptor-mediated endocytosis is an approach to active drug delivery targeted to liver cancer cells. We focus on the most recent and interesting research advances in the development of GA-based hybrid compounds and DDSs developed for potential employment as efficacious therapeutic options for the treatment of hepatic cancer

Antitumoral Effects of Glycyrrhetinic Acid
GA-Based Hybrid Molecules
GA-Functionalized Polymer-Based DDSs
GA-Functionalized Liposomes
Dual-Ligand TDDSs
Environment-Responsive GA-Functionalized DDSs
GA-Functionalized Systems for Gene Therapy
GA-Functionalized Biomaterials for Photodynamic Therapy
Findings
10. Conclusions
Full Text
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