Co-delivery of three synergistic chemotherapeutics in a core-shell nanoscale coordination polymer for the treatment of pancreatic cancer.
Biomaterials
; 301: 122235, 2023 10.
Article
em En
| MEDLINE
| ID: mdl-37441902
ABSTRACT
The combination chemotherapy regimen FOLFIRINOX comprising folinic acid, 5-fluorouracil, irinotecan, and oxaliplatin is the first-line treatment for patients with advanced pancreatic cancer, but its use remains prohibitive for the majority of patients due to severe side effects. Here, we report a core-shell nanoscale coordination polymer (NCP) nanoparticle co-delivering a potent and synergistic combination of oxaliplatin, gemcitabine, and SN38 (OGS), for the treatment of pancreatic cancer in mouse models. OGS contains key synergistic components of FOLFIRINOX in a controllable drug ratio., It exhibited particle stability in blood circulation and enhanced deposition of the drugs in acidic tumor environments. In vitro, OGS showed superior cytotoxicity over free drug combinations and robust cytotoxic synergism among its three components. In vivo, OGS improved drug circulation, increased tumor deposition, and exhibited superior antitumor efficacy over the free drug combination in both subcutaneous and orthotopic pancreatic tumor models. OGS treatment achieved 75-91% tumor growth inhibition and prolonged mouse survival by 1.6- to 2.8-folds while minimizing systemic toxicities such as neutropenia, hepatotoxicity, and renal toxicity. This work uncovers a novel and clinically relevant nanomedicine strategy to co-deliver synergistic combination chemotherapies for difficult-to-treat cancers.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
Limite:
Animals
Idioma:
En
Revista:
Biomaterials
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Estados Unidos