Abstract
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer and is characterized by poor clinical outcomes, with the majority of patients not being eligible for curative therapy and treatments only being applicable for early-stage tumors. CD44 is a receptor for hyaluronic acid (HA) and is involved in HCC progression. The aim of this work is to propose HA- and PEGylated-liposomes as promising approaches for the treatment of HCC. It has been found, in this work, that CD44 transcripts are up-regulated in HCC patients, as well as in a murine model of NAFLD/NASH-related hepatocarcinogenesis. Cell culture experiments indicate that HA-liposomes are more rapidly and significantly internalized by Huh7 cells that over-express CD44, compared with HepG2 cells that express low levels of the receptor, in which the uptake seems due to endocytic events. By contrast, human and murine macrophage cell lines (THP-1, RAW264.7) show improved and rapid uptake of PEG-modified liposomes without the involvement of the CD44. Moreover, the internalization of PEG-modified liposomes seems to induce polarization of THP1 towards the M1 phenotype. In conclusion, data reported in this study indicate that this strategy can be proposed as an alternative for drug delivery and one that dually and specifically targets liver cancer cells and infiltrating tumor macrophages in order to counteract two crucial aspect of HCC progression.
Highlights
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer
The phospholipid chain was incorporated into the liposome membrane, while the hyaluronic acid (HA) was exposed toward the aqueous phase
Literature data and clinical practice have recently underlined the alarming increase in HCC incidence at earlier stages in non-cirrhotic non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) patients
Summary
Hepatocellular carcinoma (HCC) is the most frequent primary liver cancer It is ranked as the fifth most common malignancy and the fourth leading cause of cancer-related mortality worldwide, with an incidence that continues to increase [1,2]. HCC, whatever the etiology, usually develops in conditions of chronic liver disease (CLD), mostly in the context of a cirrhotic liver, where inflammation and fibrosis promote tumor progression and resistance to therapy [3]. Between 20% and 30% of NAFLD patients develop non-alcoholic steatohepatitis (NASH), which is accompanied by a chronic inflammatory response and fibrogenesis that lead to liver injury and eventually progress to HCC [4,5,6]. Any single event/player that contributes to NAFLD/NASH-related HCC development, including inflammation (i.e., inflammatory cells) and tumor/stroma interactions, can be considered a potential therapeutic target
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
