Targeting the Tumor Core: Hypoxia-Responsive Nanoparticles for the Delivery of Chemotherapy to Pancreatic Tumors.
hypoxia-responsive
nanoparticles
pancreatic cancer
polymersomes
tumor-penetrating
Journal
Molecular pharmaceutics
ISSN: 1543-8392
Titre abrégé: Mol Pharm
Pays: United States
ID NLM: 101197791
Informations de publication
Date de publication:
03 08 2020
03 08 2020
Historique:
pubmed:
11
6
2020
medline:
29
6
2021
entrez:
11
6
2020
Statut:
ppublish
Résumé
In pancreatic ductal adenocarcinoma (PDAC), early onset of hypoxia triggers remodeling of the extracellular matrix, epithelial-to-mesenchymal transition, increased cell survival, the formation of cancer stem cells, and drug resistance. Hypoxia in PDAC is also associated with the development of collagen-rich, fibrous extracellular stroma (desmoplasia), resulting in severely impaired drug penetration. To overcome these daunting challenges, we created polymer nanoparticles (polymersomes) that target and penetrate pancreatic tumors, reach the hypoxic niches, undergo rapid structural destabilization, and release the encapsulated drugs. In vitro studies indicated a high cellular uptake of the polymersomes and increased cytotoxicity of the drugs under hypoxia compared to unencapsulated drugs. The polymersomes decreased tumor growth by nearly 250% and significantly increased necrosis within the tumors by 60% in mice compared to untreated controls. We anticipate that these polymer nanoparticles possess a considerable translational potential for delivering drugs to solid hypoxic tumors.
Identifiants
pubmed: 32521162
doi: 10.1021/acs.molpharmaceut.0c00247
pmc: PMC8114572
mid: NIHMS1693084
doi:
Substances chimiques
Antineoplastic Agents
0
Polymers
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2849-2863Subventions
Organisme : NCI NIH HHS
ID : P30 CA036727
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA210240
Pays : United States
Organisme : NIGMS NIH HHS
ID : U54 GM128729
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM109024
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM114080
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA127297
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA211462
Pays : United States
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