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Article Publish Status: FREE
Abstract Title:

An enhanced antioxidant strategy of astaxanthin encapsulated in ROS-responsive nanoparticles for combating cisplatin-induced ototoxicity.

Abstract Source:

J Nanobiotechnology. 2022 Jun 10 ;20(1):268. Epub 2022 Jun 10. PMID: 35689218

Abstract Author(s):

Jiayi Gu, Xueling Wang, Yuming Chen, Ke Xu, Dehong Yu, Hao Wu

Article Affiliation:

Jiayi Gu

Abstract:

BACKGROUND: Excessive accumulation of reactive oxygen species (ROS) has been documented as the crucial cellular mechanism of cisplatin-induced ototoxicity. However, numerous antioxidants have failed in clinical studies partly due to inefficient drug delivery to the cochlea. A drug delivery system is an attractive strategy to overcome this drawback.

METHODS AND RESULTS: In the present study, we proposed the combination of antioxidant astaxanthin (ATX) and ROS-responsive/consuming nanoparticles (PPS-NP) to combat cisplatin-induced ototoxicity. ATX-PPS-NP were constructed by the self-assembly of an amphiphilic hyperbranched polyphosphoester containing thioketal units, which scavenged ROS and disintegrate to release the encapsulated ATX. The ROS-sensitivity was confirmed byH nuclear magnetic resonance spectroscopy, transmission electron microscopy and an HOON/OFF stimulated model. Enhanced release profiles stimulated by HOwere verified in artificial perilymph, the HEI-OC1 cell line and guinea pigs. In addition, ATX-PPS-NP efficiently inhibited cisplatin-induced HEI-OC1 cell cytotoxicity and apoptosis compared with ATX or PPS-NP alone, suggesting an enhanced effect of the combination of the natural active compound ATX and ROS-consuming PPS-NP. Moreover, ATX-PPS-NP attenuated outer hair cell losses in cultured organ of Corti. In guinea pigs, NiRe-PPS-NP verified a quick penetration across the round window membrane and ATX-PPS-NP showed protective effect on spiral ganglion neurons, which further attenuated cisplatin-induced moderate hearing loss. Further studies revealed that the protective mechanisms involved decreasing excessive ROS generation, reducing inflammatory chemokine (interleukin-6) release, increasing antioxidant glutathione expression and inhibiting the mitochondrial apoptotic pathway.

CONCLUSIONS: Thus, this ROS-responsive nanoparticle encapsulating ATX has favorable potential in the prevention of cisplatin-induced hearing loss.

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