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

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

  • J Nanobiotechnology. 2022 Jun 10;20(1):268. doi: 10.1186/s12951-022-01485-8.
Jiayi Gu  # 1 2 3,  Xueling Wang  # 1 2 3,  Yuming Chen 1 2 3,  Ke Xu 1 2 3,  Dehong Yu 4 5 6 7,  Hao Wu 8 9 10
Affiliations

Affiliations

  • 1 Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 2 Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 3 Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases (14DZ2260300), Shanghai, China.
  • 4 Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. dehongyu@126.com.
  • 5 Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China. dehongyu@126.com.
  • 6 Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases (14DZ2260300), Shanghai, China. dehongyu@126.com.
  • 7 Materdicine Lab, School of Life Sciences, Shanghai University, Shanghai, China. dehongyu@126.com.
  • 8 Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wuhao@shsmu.edu.cn.
  • 9 Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China. wuhao@shsmu.edu.cn.
  • 10 Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases (14DZ2260300), Shanghai, China. wuhao@shsmu.edu.cn.
  • # Contributed equally.
PMID: 35689218 DOI: 10.1186/s12951-022-01485-8
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 by 1H nuclear magnetic resonance spectroscopy, transmission electron microscopy and an H2O2 ON/OFF stimulated model. Enhanced release profiles stimulated by H2O2 were 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.

Keywords

Astaxanthin; Cisplatin-induced ototoxicity; Poly(propylene sulfide); ROS-responsive.

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