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The Development of a Nano-based Approach to Alleviate Cisplatin-Induced Ototoxicity

  • Mohammad N. Kayyali
  • Andrew J. Ramsey
  • Elizabeth M. Higbee-Dempsey
  • Lesan Yan
  • Bert W. O’MalleyJr
  • Andrew Tsourkas
  • Daqing Li
Research Article

Abstract

Cisplatin-induced hearing loss is experienced by a high percentage of patients with squamous cell carcinoma undergoing cisplatin chemotherapy. A novel nano-construct capable of sequestering extracellular cisplatin was developed to combat this problem. The nano-construct consisted of superparamagnetic iron oxide nanoparticles (SPIONs) entrapped within polymeric micelles, which were formed from a glutathione diethyl ester-conjugated amphiphilic diblock copolymer. The glutathione-micelles were analyzed at the cellular level and in an organotypic study for safety evaluation. All utilized methods indicated that the micelles do not cause cellular toxicity or organ damage. The micelles’ ability to reduce cisplatin-induced cytotoxicity was then probed in an in vitro model. Cisplatin was pre-treated with the novel nano-construct before being added to growing cells. When compared to cells that were exposed to untreated cisplatin, cells in the pre-treated cisplatin group showed a significant increase in cell viability. This clearly demonstrates that the construct is able to protect the cells from cisplatin cytotoxicity and makes it highly likely that the novel nano-construct will be able to play a role in the protection of the inner ear from cisplatin-induced ototoxicity.

Keywords

cisplatin thiol nanomicelles cisplatin-induced ototoxicity inner ear 

Notes

Acknowledgements

This work was funded through a National Institute of Health (NIH) grant: 1R01DC014464-01. The authors would like to thank Zheng Cui and Lucia Morstadt for their technical assistance. The authors would also like to thank Dr. Kalinec at UCLA for the donation of the HEI-OC1 cell line.

Compliance with Ethical Standards

Animal care and use was in accordance with the guidelines of the Institutional Animal Care and Use Committee (IACUC) of The University of Pennsylvania and of the National Institute of Health.

Conflict of Interest

The authors declare that they have no conflicts of interest.

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Copyright information

© Association for Research in Otolaryngology 2018

Authors and Affiliations

  • Mohammad N. Kayyali
    • 1
  • Andrew J. Ramsey
    • 1
  • Elizabeth M. Higbee-Dempsey
    • 2
  • Lesan Yan
    • 2
  • Bert W. O’MalleyJr
    • 1
  • Andrew Tsourkas
    • 2
  • Daqing Li
    • 1
  1. 1.Department of Otolaryngology - Head & Neck SurgeryUniversity of Pennsylvania Health SystemPhiladelphiaUSA
  2. 2.Department of BioengineeringUniversity of PennsylvaniaPhiladelphiaUSA

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