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Reducing Postoperative Recurrence of Early‐Stage Hepatocellular Carcinoma by a Wound‐Targeted Nanodrug
New strategies to decrease risk of relapse after surgery are needed for improving 5‐year survival rate of hepatocellular carcinoma (HCC). To address this need, a wound‐targeted nanodrug is developed, that contains an immune checkpoint inhibitor (anti‐PD‐L1)and an angiogenesis inhibitor (sorafenib))....
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284141/ https://www.ncbi.nlm.nih.gov/pubmed/35524631 http://dx.doi.org/10.1002/advs.202200477 |
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author | li, Bozhao Zhang, Xiuping Wu, Zhouliang Chu, Tianjiao Yang, Zhenlin Xu, Shuai Wu, Suying Qie, Yunkai Lu, Zefang Qi, Feilong Hu, Minggen Zhao, Guodong Wei, Jingyan Zhao, Yuliang Nie, Guangjun Meng, Huan Liu, Rong Li, Suping |
author_facet | li, Bozhao Zhang, Xiuping Wu, Zhouliang Chu, Tianjiao Yang, Zhenlin Xu, Shuai Wu, Suying Qie, Yunkai Lu, Zefang Qi, Feilong Hu, Minggen Zhao, Guodong Wei, Jingyan Zhao, Yuliang Nie, Guangjun Meng, Huan Liu, Rong Li, Suping |
author_sort | li, Bozhao |
collection | PubMed |
description | New strategies to decrease risk of relapse after surgery are needed for improving 5‐year survival rate of hepatocellular carcinoma (HCC). To address this need, a wound‐targeted nanodrug is developed, that contains an immune checkpoint inhibitor (anti‐PD‐L1)and an angiogenesis inhibitor (sorafenib)). These nanoparticles consist of highly biocompatible mesoporous silica (MSNP) that is surface‐coated with platelet membrane (PM) to achieve surgical site targeting in a self‐amplified accumulation manner. Sorafenib is introduced into the MSNP pores while covalently attaching anti‐PD‐L1 antibody on the PM surface. The resulting nano‐formulation, abbreviated as a‐PM‐S‐MSNP, can effectively target the surgical margin when intraperitoneally (IP) administered into an immune competent murine orthotopic HCC model. Multiple administrations of a‐PM‐S‐MSNP generate potent anti‐HCC effect and significantly prolong overall mice survival. Immunophenotyping and immunochemistry staining reveal the signatures of favorable anti‐HCC immunity and anti‐angiogenesis effect at tumor sites. More importantly, microscopic inspection of a‐PM‐S‐MSNP treated mice shows that 2 out 6 are histologically tumor‐free, which is in sharp contrast to the control mice where tumor foci can be easily identified. The data suggest that a‐PM‐S‐MSNP can efficiently inhibit post‐surgical HCC relapse without obvious side effects and holds considerable promise for clinical translation as a novel nanodrug. |
format | Online Article Text |
id | pubmed-9284141 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-92841412022-07-15 Reducing Postoperative Recurrence of Early‐Stage Hepatocellular Carcinoma by a Wound‐Targeted Nanodrug li, Bozhao Zhang, Xiuping Wu, Zhouliang Chu, Tianjiao Yang, Zhenlin Xu, Shuai Wu, Suying Qie, Yunkai Lu, Zefang Qi, Feilong Hu, Minggen Zhao, Guodong Wei, Jingyan Zhao, Yuliang Nie, Guangjun Meng, Huan Liu, Rong Li, Suping Adv Sci (Weinh) Research Articles New strategies to decrease risk of relapse after surgery are needed for improving 5‐year survival rate of hepatocellular carcinoma (HCC). To address this need, a wound‐targeted nanodrug is developed, that contains an immune checkpoint inhibitor (anti‐PD‐L1)and an angiogenesis inhibitor (sorafenib)). These nanoparticles consist of highly biocompatible mesoporous silica (MSNP) that is surface‐coated with platelet membrane (PM) to achieve surgical site targeting in a self‐amplified accumulation manner. Sorafenib is introduced into the MSNP pores while covalently attaching anti‐PD‐L1 antibody on the PM surface. The resulting nano‐formulation, abbreviated as a‐PM‐S‐MSNP, can effectively target the surgical margin when intraperitoneally (IP) administered into an immune competent murine orthotopic HCC model. Multiple administrations of a‐PM‐S‐MSNP generate potent anti‐HCC effect and significantly prolong overall mice survival. Immunophenotyping and immunochemistry staining reveal the signatures of favorable anti‐HCC immunity and anti‐angiogenesis effect at tumor sites. More importantly, microscopic inspection of a‐PM‐S‐MSNP treated mice shows that 2 out 6 are histologically tumor‐free, which is in sharp contrast to the control mice where tumor foci can be easily identified. The data suggest that a‐PM‐S‐MSNP can efficiently inhibit post‐surgical HCC relapse without obvious side effects and holds considerable promise for clinical translation as a novel nanodrug. John Wiley and Sons Inc. 2022-05-07 /pmc/articles/PMC9284141/ /pubmed/35524631 http://dx.doi.org/10.1002/advs.202200477 Text en © 2022 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles li, Bozhao Zhang, Xiuping Wu, Zhouliang Chu, Tianjiao Yang, Zhenlin Xu, Shuai Wu, Suying Qie, Yunkai Lu, Zefang Qi, Feilong Hu, Minggen Zhao, Guodong Wei, Jingyan Zhao, Yuliang Nie, Guangjun Meng, Huan Liu, Rong Li, Suping Reducing Postoperative Recurrence of Early‐Stage Hepatocellular Carcinoma by a Wound‐Targeted Nanodrug |
title | Reducing Postoperative Recurrence of Early‐Stage Hepatocellular Carcinoma by a Wound‐Targeted Nanodrug |
title_full | Reducing Postoperative Recurrence of Early‐Stage Hepatocellular Carcinoma by a Wound‐Targeted Nanodrug |
title_fullStr | Reducing Postoperative Recurrence of Early‐Stage Hepatocellular Carcinoma by a Wound‐Targeted Nanodrug |
title_full_unstemmed | Reducing Postoperative Recurrence of Early‐Stage Hepatocellular Carcinoma by a Wound‐Targeted Nanodrug |
title_short | Reducing Postoperative Recurrence of Early‐Stage Hepatocellular Carcinoma by a Wound‐Targeted Nanodrug |
title_sort | reducing postoperative recurrence of early‐stage hepatocellular carcinoma by a wound‐targeted nanodrug |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284141/ https://www.ncbi.nlm.nih.gov/pubmed/35524631 http://dx.doi.org/10.1002/advs.202200477 |
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