Mitochondria-homing peptide functionalized nanoparticles performing dual extracellular/intracellular roles to inhibit aminoglycosides induced ototoxicity.
Artif Cells Nanomed Biotechnol
; 46(sup2): 314-323, 2018.
Article
en En
| MEDLINE
| ID: mdl-29595337
ABSTRACT
One of the major challenges in the treatment of hearing loss is the low efficacy of therapeutic candidates. To achieve the optimum drug efficacy, we designed a novel peptide (D-Arg-Dmt-Arg-Phe-NH2)-mediated mitochondrial targeted delivery nanosystem for a promising candidate, geranylgeranylacetone (GGA). The zebrafish lateral line system, a robust model for mammalian hair cells, was used to identify the efficacy against gentamicin, a well-known ototoxic agent. The nanosystem facilitated lysosomal escape and mitochondrial accumulation, and thus conferred superior protective efficacy against a wide range of gentamicin compared with unmodified NPs and free drugs. Meanwhile, peptides-modified NPs internalized hair cells via both of dynamin-dependent and independent routes, following a classic endocytic or autophagy pathway. Although extracellular action via MET channels, the primary protective mechanism underlying peptides-modified NPs was revealed due to their intracellular interaction. Thus, our nanoplatform provided a general strategy to enhance the clinical efficacy of a broad range of drugs in the treatment of hearing loss.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Oligopéptidos
/
Espacio Intracelular
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Oído
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Espacio Extracelular
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Nanopartículas
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Aminoglicósidos
/
Mitocondrias
Límite:
Animals
Idioma:
En
Revista:
Artif Cells Nanomed Biotechnol
Año:
2018
Tipo del documento:
Article