Nanoparticles for urothelium penetration and delivery of the histone deacetylase inhibitor belinostat for treatment of bladder cancer.
Nanomedicine
; 9(8): 1124-34, 2013 Nov.
Article
em En
| MEDLINE
| ID: mdl-23764660
ABSTRACT
Nearly 40% of patients with non-invasive bladder cancer will progress to invasive disease despite locally-directed therapy. Overcoming the bladder permeability barrier (BPB) is a challenge for intravesical drug delivery. Using the fluorophore coumarin (C6), we synthesized C6-loaded poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs), which were surface modified with a novel cell penetrating polymer, poly(guanidinium oxanorbornene) (PGON). Addition of PGON to the NP surface improved tissue penetration by 10-fold in intravesically-treated mouse bladder and ex vivo human ureter. In addition, NP-C6-PGON significantly enhanced intracellular uptake of NPs compared to NPs without PGON. To examine biological activity, we synthesized NPs that were loaded with the histone deacetylase (HDAC) inhibitor belinostat (NP-Bel-PGON). NP-Bel-PGON exhibited a significantly lower IC50 in cultured bladder cancer cells, and sustained hyperacetylation, when compared to unencapsulated belinostat. Xenograft tumors treated with NP-Bel-PGON showed a 70% reduction in volume, and a 2.5-fold higher intratumoral acetyl-H4, when compared to tumors treated with unloaded NP-PGON. FROM THE CLINICAL EDITOR These authors demonstrate that PLGA nanoparticles with PGON surface functionalization result in greatly enhanced cell penetrating capabilities, and present convincing data from a mouse model of bladder cancer for increased chemotherapy efficacy.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sulfonamidas
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Neoplasias da Bexiga Urinária
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Portadores de Fármacos
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Nanopartículas
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Inibidores de Histona Desacetilases
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Ácidos Hidroxâmicos
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Nanomedicine
Assunto da revista:
BIOTECNOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article