2. Academic Validation
  3. Targeting Cell Membranes, Depleting ROS by Dithiane and Thioketal-Containing Polymers with Pendant Cholesterols Delivering Necrostatin-1 for Glaucoma Treatment

Targeting Cell Membranes, Depleting ROS by Dithiane and Thioketal-Containing Polymers with Pendant Cholesterols Delivering Necrostatin-1 for Glaucoma Treatment

  • ACS Nano. 2022 Dec 9. doi: 10.1021/acsnano.2c09202.
Rong Rong 1 2 3,  Xuezhi Zhou 1 2 3,  Ganghao Liang 4 5,  Haibo Li 1 2 3,  Mengling You 1 2 3,  Zhuotao Liang 3 6,  Zhou Zeng 1 2 3,  Haihua Xiao 4 5,  Dan Ji 1 2 3,  Xiaobo Xia 1 2 3
Affiliations

Affiliations

  • 1 Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan410008, P. R. China.
  • 2 Hunan Key Laboratory of Ophthalmology, Changsha, Hunan410008, P. R. China.
  • 3 National Clinical Research Center for Geriatric Diseases (Xiangya Hospital), Central South University, Changsha, Hunan410008, P. R. China.
  • 4 Beijing National Laboratory for Molecular Sciences, State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, Chinese Academy of Sciences, Beijing100190, China.
  • 5 University of Chinese Academy of Sciences, Beijing100049, China.
  • 6 Department of Spine Surgery, Xiangya Hospital, Central South University, Changsha, Hunan410008, P. R. China.
PMID: 36487191 DOI: 10.1021/acsnano.2c09202
Abstract

Glaucoma is the leading cause of irreversible blindness worldwide, characterized by progressive vision loss due to the selective damage to retinal ganglion cells (RGCs) and their axons. Oxidative stress is generally believed as one key factor of RGCs death. Recently, Necroptosis was identified to play a key role in glaucomatous injury. Therefore, depletion of Reactive Oxygen Species (ROS) and inhibition of Necroptosis in RGCs has become one of treatment strategies for glaucoma. However, existing drugs without efficient drug enter into the retina and have controlled release due to a short drug retention. Herein, we designed a glaucomatous microenvironment-responsive drug carrier polymer, which is characterized by the presence of thioketal bonds and 1,4-dithiane unit in the main chain for depleting ROS as well as the pendant cholesterols for targeting cell membranes. This polymer was adopted to encapsulate an inhibitor of Necroptosis, necrostatin-1, into nanoparticles (designated as NP1). NP1 with superior biosafety could scavenge ROS in RGCs both in vitro and in vivo of an acute pathological glaucomatous injury model. Further, NP1 was found to effectively inhibit the upregulation of the Necroptosis pathway, reducing the death of RGCs. The findings in this study exemplified the use of nanomaterials as potential strategies to treat glaucoma.

Keywords

glaucoma; nanoparticle; necroptosis; reactive oxygen species; retinal ganglion cell.

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