A polymeric nanocarrier with a tumor acidity-activatable arginine-rich (R9) peptide for enhanced drug delivery.
Biomater Sci
; 8(8): 2255-2263, 2020 Apr 15.
Article
en En
| MEDLINE
| ID: mdl-32129378
ABSTRACT
Cell-penetrating peptides (CPPs) have been considered as a powerful tool to improve the intracellular and nuclear delivery efficiency of nanocarriers. However, their clinical application is limited because of their nonspecific targeting function, short half-life, and severe system toxicity. Herein, we have developed a polymeric nanocarrier with a tumor acidity-activatable arginine-rich (R9) peptide for targeted drug delivery. The nanocarrier is fabricated with a R9-conjugated amphiphilic diblock polymer of poly(ethylene glycol) (PEG) and poly(hexyl ethylene phosphate) (PHEP), and then further coated with tumor acidity-activatable polyanionic polyphosphoester through electrostatic interaction in order to block the nonspecific targeting function of the R9 peptide. In the slightly acidic tumor extracellular environment (â¼pH 6.5), tumor acidity-activatable polyanionic polyphosphoester would be deshielded from the nanoparticles, resulting in the re-exposure of the R9 peptide to enhance tumor cellular uptake. As a result, intracellular concentration of payload in 4T1 tumor cells significantly increased at pH 6.5. And, we further demonstrate that such a delivery system remarkably promoted the anti-tumor efficiency of chemotherapeutic drugs in tumor-bearing mice, offering great potential for drug delivery and cancer therapy.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Polímeros
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Portadores de Fármacos
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Doxorrubicina
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Nanopartículas
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Neoplasias Mamarias Experimentales
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Antibióticos Antineoplásicos
Límite:
Animals
Idioma:
En
Revista:
Biomater Sci
Año:
2020
Tipo del documento:
Article