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Hepatocyte-targeting and tumor microenvironment-responsive liposomes for enhanced anti-hepatocarcinoma efficacy
To increase the antitumor drug concentration in the liver tumor site and improve the therapeutic effects, a functionalized liposome (PPP-LIP) with tumor targetability and enhanced internalization after matrix metalloproteinase-2 (MMP2)-triggered cell-penetrating peptide (TATp) exposure was modified...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487930/ https://www.ncbi.nlm.nih.gov/pubmed/36104946 http://dx.doi.org/10.1080/10717544.2022.2122635 |
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author | Cheng, Dongliang Wen, Zhiwei Chen, Hui Lin, Shiyuan Zhang, Wei Tang, Xin Wu, Wei |
author_facet | Cheng, Dongliang Wen, Zhiwei Chen, Hui Lin, Shiyuan Zhang, Wei Tang, Xin Wu, Wei |
author_sort | Cheng, Dongliang |
collection | PubMed |
description | To increase the antitumor drug concentration in the liver tumor site and improve the therapeutic effects, a functionalized liposome (PPP-LIP) with tumor targetability and enhanced internalization after matrix metalloproteinase-2 (MMP2)-triggered cell-penetrating peptide (TATp) exposure was modified with myrcludex B (a synthetic HBV preS-derived lipopeptide endowed with compelling liver tropism) for liver tumor-specific delivery. After intravenous administration, PPP-LIP was mediated by myrcludex B to reach the hepatocyte surface. The MMP2-overexpressing tumor microenvironment deprotected PEG, exposing it to TATp, facilitating tumor penetration and subsequent efficient destruction of tumor cells. In live imaging of small animals and cellular uptake, PPP-LIP was taken up much more than typical unmodified liposomes in the ICR mouse liver and liver tumor cells. Hydroxycamptothecin (HCPT)-loaded PPP-LIP showed a better antitumor effect than commercially available HCPT injections among MTT, three-dimensional (3 D) tumor ball, and tumor-bearing nude mouse experiments. Our findings indicated that PPP-LIP nanocarriers could be a promising tumor-targeted medication delivery strategy for treating liver cancers with elevated MMP2 expression. |
format | Online Article Text |
id | pubmed-9487930 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-94879302022-09-21 Hepatocyte-targeting and tumor microenvironment-responsive liposomes for enhanced anti-hepatocarcinoma efficacy Cheng, Dongliang Wen, Zhiwei Chen, Hui Lin, Shiyuan Zhang, Wei Tang, Xin Wu, Wei Drug Deliv Research Article To increase the antitumor drug concentration in the liver tumor site and improve the therapeutic effects, a functionalized liposome (PPP-LIP) with tumor targetability and enhanced internalization after matrix metalloproteinase-2 (MMP2)-triggered cell-penetrating peptide (TATp) exposure was modified with myrcludex B (a synthetic HBV preS-derived lipopeptide endowed with compelling liver tropism) for liver tumor-specific delivery. After intravenous administration, PPP-LIP was mediated by myrcludex B to reach the hepatocyte surface. The MMP2-overexpressing tumor microenvironment deprotected PEG, exposing it to TATp, facilitating tumor penetration and subsequent efficient destruction of tumor cells. In live imaging of small animals and cellular uptake, PPP-LIP was taken up much more than typical unmodified liposomes in the ICR mouse liver and liver tumor cells. Hydroxycamptothecin (HCPT)-loaded PPP-LIP showed a better antitumor effect than commercially available HCPT injections among MTT, three-dimensional (3 D) tumor ball, and tumor-bearing nude mouse experiments. Our findings indicated that PPP-LIP nanocarriers could be a promising tumor-targeted medication delivery strategy for treating liver cancers with elevated MMP2 expression. Taylor & Francis 2022-09-14 /pmc/articles/PMC9487930/ /pubmed/36104946 http://dx.doi.org/10.1080/10717544.2022.2122635 Text en © 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Cheng, Dongliang Wen, Zhiwei Chen, Hui Lin, Shiyuan Zhang, Wei Tang, Xin Wu, Wei Hepatocyte-targeting and tumor microenvironment-responsive liposomes for enhanced anti-hepatocarcinoma efficacy |
title | Hepatocyte-targeting and tumor microenvironment-responsive liposomes for enhanced anti-hepatocarcinoma efficacy |
title_full | Hepatocyte-targeting and tumor microenvironment-responsive liposomes for enhanced anti-hepatocarcinoma efficacy |
title_fullStr | Hepatocyte-targeting and tumor microenvironment-responsive liposomes for enhanced anti-hepatocarcinoma efficacy |
title_full_unstemmed | Hepatocyte-targeting and tumor microenvironment-responsive liposomes for enhanced anti-hepatocarcinoma efficacy |
title_short | Hepatocyte-targeting and tumor microenvironment-responsive liposomes for enhanced anti-hepatocarcinoma efficacy |
title_sort | hepatocyte-targeting and tumor microenvironment-responsive liposomes for enhanced anti-hepatocarcinoma efficacy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9487930/ https://www.ncbi.nlm.nih.gov/pubmed/36104946 http://dx.doi.org/10.1080/10717544.2022.2122635 |
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