Sandwich-Structured Implants to Obstruct Multipath Energy Supply and Trigger Self-Enhanced Hypoxia-Initiated Chemotherapy Against Postsurgical Tumor Recurrence and Metastasis.
3D printing
electrospinning
hypoxia-triggered chemotherapy
in situ delivery
starvation therapy
Journal
Advanced science (Weinheim, Baden-Wurttemberg, Germany)
ISSN: 2198-3844
Titre abrégé: Adv Sci (Weinh)
Pays: Germany
ID NLM: 101664569
Informations de publication
Date de publication:
08 2023
08 2023
Historique:
revised:
03
04
2023
received:
09
02
2023
medline:
7
8
2023
pubmed:
9
5
2023
entrez:
8
5
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37156756
doi: 10.1002/advs.202300899
pmc: PMC10401165
doi:
Substances chimiques
Vascular Endothelial Growth Factor A
0
Antineoplastic Agents
0
Tirapazamine
1UD32YR59G
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2300899Subventions
Organisme : National Key Research and Development Program of China
ID : 2019YFA0111300
Organisme : National Natural Science Foundation of China
ID : 22277155
Organisme : National Natural Science Foundation of China
ID : 22002190
Organisme : National Natural Science Foundation of China
ID : 52202359
Organisme : National Natural Science Foundation of China
ID : 32001012
Organisme : Science and Technology Program of Guangzhou
ID : 202102010225
Organisme : Science and Technology Program of Guangzhou
ID : 202102010217
Organisme : China Primary Health Care Foundation
ID : 2022-003
Organisme : China Postdoctoral Science Foundation
ID : 2021M693674
Organisme : Guangdong Provincial Pearl River Talents Program
ID : 2019QN01Y131
Organisme : Natural Science Foundation of Guangdong Province
ID : 2023A1515011083
Organisme : Thousand Talents Plan
Informations de copyright
© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.
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