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Sandwich‐Structured Implants to Obstruct Multipath Energy Supply and Trigger Self‐Enhanced Hypoxia‐Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis
As a currently common strategy to treat cancer, surgical resection may cause tumor recurrence and metastasis due to residual postoperative tumors. Herein, an implantable sandwich‐structured dual‐drug depot is developed to trigger a self‐intensified starvation therapy and hypoxia‐induced chemotherapy...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10401165/ https://www.ncbi.nlm.nih.gov/pubmed/37156756 http://dx.doi.org/10.1002/advs.202300899 |
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author | Fang, Youqiang Luo, Xing Xu, Yanteng Liu, Zheng Mintz, Rachel L. Yu, Haiyang Yu, Xuan Li, Kai Ju, Enguo Wang, Haixia Tang, Zhaohui Tao, Yu Li, Mingqiang |
author_facet | Fang, Youqiang Luo, Xing Xu, Yanteng Liu, Zheng Mintz, Rachel L. Yu, Haiyang Yu, Xuan Li, Kai Ju, Enguo Wang, Haixia Tang, Zhaohui Tao, Yu Li, Mingqiang |
author_sort | Fang, Youqiang |
collection | PubMed |
description | As a currently common strategy to treat cancer, surgical resection may cause tumor recurrence and metastasis due to residual postoperative tumors. Herein, an implantable sandwich‐structured dual‐drug depot is developed to trigger a self‐intensified starvation therapy and hypoxia‐induced chemotherapy sequentially. The two outer layers are 3D‐printed using a calcium‐crosslinked mixture ink containing soy protein isolate, polyvinyl alcohol, sodium alginate, and combretastatin A4 phosphate (CA4P). The inner layer is one patch of poly (lactic‐co‐glycolic acid)‐based electrospun fibers loaded with tirapazamine (TPZ). The preferentially released CA4P destroys the preexisting blood vessels and prevents neovascularization, which obstructs the external energy supply to cancer cells but aggravates hypoxic condition. The subsequently released TPZ is bioreduced to cytotoxic benzotriazinyl under hypoxia, further damaging DNA, generating reactive oxygen species, disrupting mitochondria, and downregulating hypoxia‐inducible factor 1α, vascular endothelial growth factor, and matrix metalloproteinase 9. Together these processes induce apoptosis, block the intracellular energy supply, counteract the disadvantage of CA4P in favoring intratumor angiogenesis, and suppress tumor metastasis. The in vivo and in vitro results and the transcriptome analysis demonstrate that the postsurgical adjuvant treatment with the dual‐drug‐loaded sandwich‐like implants efficiently inhibits tumor recurrence and metastasis, showing great potential for clinical translation. |
format | Online Article Text |
id | pubmed-10401165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-104011652023-08-05 Sandwich‐Structured Implants to Obstruct Multipath Energy Supply and Trigger Self‐Enhanced Hypoxia‐Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis Fang, Youqiang Luo, Xing Xu, Yanteng Liu, Zheng Mintz, Rachel L. Yu, Haiyang Yu, Xuan Li, Kai Ju, Enguo Wang, Haixia Tang, Zhaohui Tao, Yu Li, Mingqiang Adv Sci (Weinh) Research Articles As a currently common strategy to treat cancer, surgical resection may cause tumor recurrence and metastasis due to residual postoperative tumors. Herein, an implantable sandwich‐structured dual‐drug depot is developed to trigger a self‐intensified starvation therapy and hypoxia‐induced chemotherapy sequentially. The two outer layers are 3D‐printed using a calcium‐crosslinked mixture ink containing soy protein isolate, polyvinyl alcohol, sodium alginate, and combretastatin A4 phosphate (CA4P). The inner layer is one patch of poly (lactic‐co‐glycolic acid)‐based electrospun fibers loaded with tirapazamine (TPZ). The preferentially released CA4P destroys the preexisting blood vessels and prevents neovascularization, which obstructs the external energy supply to cancer cells but aggravates hypoxic condition. The subsequently released TPZ is bioreduced to cytotoxic benzotriazinyl under hypoxia, further damaging DNA, generating reactive oxygen species, disrupting mitochondria, and downregulating hypoxia‐inducible factor 1α, vascular endothelial growth factor, and matrix metalloproteinase 9. Together these processes induce apoptosis, block the intracellular energy supply, counteract the disadvantage of CA4P in favoring intratumor angiogenesis, and suppress tumor metastasis. The in vivo and in vitro results and the transcriptome analysis demonstrate that the postsurgical adjuvant treatment with the dual‐drug‐loaded sandwich‐like implants efficiently inhibits tumor recurrence and metastasis, showing great potential for clinical translation. John Wiley and Sons Inc. 2023-05-08 /pmc/articles/PMC10401165/ /pubmed/37156756 http://dx.doi.org/10.1002/advs.202300899 Text en © 2023 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 Fang, Youqiang Luo, Xing Xu, Yanteng Liu, Zheng Mintz, Rachel L. Yu, Haiyang Yu, Xuan Li, Kai Ju, Enguo Wang, Haixia Tang, Zhaohui Tao, Yu Li, Mingqiang Sandwich‐Structured Implants to Obstruct Multipath Energy Supply and Trigger Self‐Enhanced Hypoxia‐Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis |
title | Sandwich‐Structured Implants to Obstruct Multipath Energy Supply and Trigger Self‐Enhanced Hypoxia‐Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis |
title_full | Sandwich‐Structured Implants to Obstruct Multipath Energy Supply and Trigger Self‐Enhanced Hypoxia‐Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis |
title_fullStr | Sandwich‐Structured Implants to Obstruct Multipath Energy Supply and Trigger Self‐Enhanced Hypoxia‐Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis |
title_full_unstemmed | Sandwich‐Structured Implants to Obstruct Multipath Energy Supply and Trigger Self‐Enhanced Hypoxia‐Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis |
title_short | Sandwich‐Structured Implants to Obstruct Multipath Energy Supply and Trigger Self‐Enhanced Hypoxia‐Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis |
title_sort | sandwich‐structured implants to obstruct multipath energy supply and trigger self‐enhanced hypoxia‐initiated chemotherapy against postsurgical tumor recurrence and metastasis |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10401165/ https://www.ncbi.nlm.nih.gov/pubmed/37156756 http://dx.doi.org/10.1002/advs.202300899 |
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