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Implantable Bioresponsive Hydrogel Prevents Local Recurrence of Breast Cancer by Enhancing Radiosensitivity

Breast cancer is one of the most common types of cancer. Patients are often concerned about regional recurrence after breast cancer surgery. Radiotherapy plays a vital role in reducing recurrence and prolonging the survival of patients undergoing breast-conserving surgery and high-risk mastectomy. H...

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Autores principales: Fu, Zhiguang, Li, Hongqi, Xue, Peng, Yu, Hanying, Yang, Shuo, Tao, Cheng, Li, Wei, Wang, Yingjie, Zhang, Jianjun, Wang, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039615/
https://www.ncbi.nlm.nih.gov/pubmed/35497337
http://dx.doi.org/10.3389/fbioe.2022.881544
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author Fu, Zhiguang
Li, Hongqi
Xue, Peng
Yu, Hanying
Yang, Shuo
Tao, Cheng
Li, Wei
Wang, Yingjie
Zhang, Jianjun
Wang, Yu
author_facet Fu, Zhiguang
Li, Hongqi
Xue, Peng
Yu, Hanying
Yang, Shuo
Tao, Cheng
Li, Wei
Wang, Yingjie
Zhang, Jianjun
Wang, Yu
author_sort Fu, Zhiguang
collection PubMed
description Breast cancer is one of the most common types of cancer. Patients are often concerned about regional recurrence after breast cancer surgery. Radiotherapy plays a vital role in reducing recurrence and prolonging the survival of patients undergoing breast-conserving surgery and high-risk mastectomy. However, 8–15% of patients still have disease progression due to radiation resistance. Therefore, new strategies for combination radiotherapy sensitization must be investigated. In this study, an implantable drug loading system, sunitinib nanoparticles @ matrix metalloproteinases -response hydrogel (NSMRH), uses enzyme-sensitive hydrogel as a carrier to load sunitinib nanoparticles, was identified. The releasing profile demonstrated that sunitinib nanoparticles may be continuously released from the hydrogels. Functional experiments revealed that, when paired with NSMRH, radiation may significantly inhibit tumor cell proliferation, migration, and invasion in vitro. Further animal experiments showed that NSMRH combined with radiotherapy could more effectively control the recurrence of subcutaneous xenograft tumors, prolong the survival time, and have no obvious toxicity in nude mice. Finally, by studying the molecular mechanism of NSMRH, it was hypothesized that in breast cancer cells, NSMRH cooperated with sensitized radiotherapy, mainly due to significantly blocking the G2/M phase, reducing the DNA repair efficiency, inhibiting tumor angiogenesis, promoting apoptosis, and reversing the abnormal expression of platelet-derived growth factor receptor alpha (PDGFRA) after radiotherapy. These findings suggest that NSMRH’s radiation sensitization and anti-tumor activity may aid in the development of a novel method in future clinical applications.
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spelling pubmed-90396152022-04-27 Implantable Bioresponsive Hydrogel Prevents Local Recurrence of Breast Cancer by Enhancing Radiosensitivity Fu, Zhiguang Li, Hongqi Xue, Peng Yu, Hanying Yang, Shuo Tao, Cheng Li, Wei Wang, Yingjie Zhang, Jianjun Wang, Yu Front Bioeng Biotechnol Bioengineering and Biotechnology Breast cancer is one of the most common types of cancer. Patients are often concerned about regional recurrence after breast cancer surgery. Radiotherapy plays a vital role in reducing recurrence and prolonging the survival of patients undergoing breast-conserving surgery and high-risk mastectomy. However, 8–15% of patients still have disease progression due to radiation resistance. Therefore, new strategies for combination radiotherapy sensitization must be investigated. In this study, an implantable drug loading system, sunitinib nanoparticles @ matrix metalloproteinases -response hydrogel (NSMRH), uses enzyme-sensitive hydrogel as a carrier to load sunitinib nanoparticles, was identified. The releasing profile demonstrated that sunitinib nanoparticles may be continuously released from the hydrogels. Functional experiments revealed that, when paired with NSMRH, radiation may significantly inhibit tumor cell proliferation, migration, and invasion in vitro. Further animal experiments showed that NSMRH combined with radiotherapy could more effectively control the recurrence of subcutaneous xenograft tumors, prolong the survival time, and have no obvious toxicity in nude mice. Finally, by studying the molecular mechanism of NSMRH, it was hypothesized that in breast cancer cells, NSMRH cooperated with sensitized radiotherapy, mainly due to significantly blocking the G2/M phase, reducing the DNA repair efficiency, inhibiting tumor angiogenesis, promoting apoptosis, and reversing the abnormal expression of platelet-derived growth factor receptor alpha (PDGFRA) after radiotherapy. These findings suggest that NSMRH’s radiation sensitization and anti-tumor activity may aid in the development of a novel method in future clinical applications. Frontiers Media S.A. 2022-04-12 /pmc/articles/PMC9039615/ /pubmed/35497337 http://dx.doi.org/10.3389/fbioe.2022.881544 Text en Copyright © 2022 Fu, Li, Xue, Yu, Yang, Tao, Li, Wang, Zhang and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Fu, Zhiguang
Li, Hongqi
Xue, Peng
Yu, Hanying
Yang, Shuo
Tao, Cheng
Li, Wei
Wang, Yingjie
Zhang, Jianjun
Wang, Yu
Implantable Bioresponsive Hydrogel Prevents Local Recurrence of Breast Cancer by Enhancing Radiosensitivity
title Implantable Bioresponsive Hydrogel Prevents Local Recurrence of Breast Cancer by Enhancing Radiosensitivity
title_full Implantable Bioresponsive Hydrogel Prevents Local Recurrence of Breast Cancer by Enhancing Radiosensitivity
title_fullStr Implantable Bioresponsive Hydrogel Prevents Local Recurrence of Breast Cancer by Enhancing Radiosensitivity
title_full_unstemmed Implantable Bioresponsive Hydrogel Prevents Local Recurrence of Breast Cancer by Enhancing Radiosensitivity
title_short Implantable Bioresponsive Hydrogel Prevents Local Recurrence of Breast Cancer by Enhancing Radiosensitivity
title_sort implantable bioresponsive hydrogel prevents local recurrence of breast cancer by enhancing radiosensitivity
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039615/
https://www.ncbi.nlm.nih.gov/pubmed/35497337
http://dx.doi.org/10.3389/fbioe.2022.881544
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