Mitochondria-homing peptide functionalized nanoparticles performing dual extracellular/intracellular roles to inhibit aminoglycosides induced ototoxicity.

Mitochondria-homing peptide functionalized nanoparticles performing dual extracellular/intracellular roles to inhibit aminoglycosides induced ototoxicity.

Artif Cells Nanomed Biotechnol. 2018 Mar 29;:1-10

Authors: Zhou S, Sun Y, Kuang X, Hou S, Wang Z, Qian Z, Liu H

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.

PMID: 29595337 [PubMed - as supplied by publisher]

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