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Hyaluronated and PEGylated Liposomes as a Potential Drug-Delivery Strategy to Specifically Target Liver Cancer and Inflammatory Cells

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...

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Autores principales: Cannito, Stefania, Bincoletto, Valeria, Turato, Cristian, Pontisso, Patrizia, Scupoli, Maria Teresa, Ailuno, Giorgia, Andreana, Ilaria, Stella, Barbara, Arpicco, Silvia, Bocca, Claudia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8840578/
https://www.ncbi.nlm.nih.gov/pubmed/35164326
http://dx.doi.org/10.3390/molecules27031062
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author Cannito, Stefania
Bincoletto, Valeria
Turato, Cristian
Pontisso, Patrizia
Scupoli, Maria Teresa
Ailuno, Giorgia
Andreana, Ilaria
Stella, Barbara
Arpicco, Silvia
Bocca, Claudia
author_facet Cannito, Stefania
Bincoletto, Valeria
Turato, Cristian
Pontisso, Patrizia
Scupoli, Maria Teresa
Ailuno, Giorgia
Andreana, Ilaria
Stella, Barbara
Arpicco, Silvia
Bocca, Claudia
author_sort Cannito, Stefania
collection PubMed
description 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.
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spelling pubmed-88405782022-02-13 Hyaluronated and PEGylated Liposomes as a Potential Drug-Delivery Strategy to Specifically Target Liver Cancer and Inflammatory Cells Cannito, Stefania Bincoletto, Valeria Turato, Cristian Pontisso, Patrizia Scupoli, Maria Teresa Ailuno, Giorgia Andreana, Ilaria Stella, Barbara Arpicco, Silvia Bocca, Claudia Molecules Article 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. MDPI 2022-02-04 /pmc/articles/PMC8840578/ /pubmed/35164326 http://dx.doi.org/10.3390/molecules27031062 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cannito, Stefania
Bincoletto, Valeria
Turato, Cristian
Pontisso, Patrizia
Scupoli, Maria Teresa
Ailuno, Giorgia
Andreana, Ilaria
Stella, Barbara
Arpicco, Silvia
Bocca, Claudia
Hyaluronated and PEGylated Liposomes as a Potential Drug-Delivery Strategy to Specifically Target Liver Cancer and Inflammatory Cells
title Hyaluronated and PEGylated Liposomes as a Potential Drug-Delivery Strategy to Specifically Target Liver Cancer and Inflammatory Cells
title_full Hyaluronated and PEGylated Liposomes as a Potential Drug-Delivery Strategy to Specifically Target Liver Cancer and Inflammatory Cells
title_fullStr Hyaluronated and PEGylated Liposomes as a Potential Drug-Delivery Strategy to Specifically Target Liver Cancer and Inflammatory Cells
title_full_unstemmed Hyaluronated and PEGylated Liposomes as a Potential Drug-Delivery Strategy to Specifically Target Liver Cancer and Inflammatory Cells
title_short Hyaluronated and PEGylated Liposomes as a Potential Drug-Delivery Strategy to Specifically Target Liver Cancer and Inflammatory Cells
title_sort hyaluronated and pegylated liposomes as a potential drug-delivery strategy to specifically target liver cancer and inflammatory cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8840578/
https://www.ncbi.nlm.nih.gov/pubmed/35164326
http://dx.doi.org/10.3390/molecules27031062
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