The dose threshold for nanoparticle tumour delivery.
Nat Mater
; 19(12): 1362-1371, 2020 12.
Article
en En
| MEDLINE
| ID: mdl-32778816
ABSTRACT
Nanoparticle delivery to solid tumours over the past ten years has stagnated at a median of 0.7% of the injected dose. Varying nanoparticle designs and strategies have yielded only minor improvements. Here we discovered a dose threshold for improving nanoparticle tumour delivery 1 trillion nanoparticles in mice. Doses above this threshold overwhelmed Kupffer cell uptake rates, nonlinearly decreased liver clearance, prolonged circulation and increased nanoparticle tumour delivery. This enabled up to 12% tumour delivery efficiency and delivery to 93% of cells in tumours, and also improved the therapeutic efficacy of Caelyx/Doxil. This threshold was robust across different nanoparticle types, tumour models and studies across ten years of the literature. Our results have implications for human translation and highlight a simple, but powerful, principle for designing nanoparticle cancer treatments.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Doxorrubicina
/
Sistemas de Liberación de Medicamentos
/
Nanopartículas
/
Neoplasias Experimentales
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Nat Mater
Asunto de la revista:
CIENCIA
/
QUIMICA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Canadá