2. Academic Validation
  3. Disulfide-Appended siRNA Nanoeyedrops: Noninvasive Gene Therapy for Targeting Retinal Angiogenesis

Disulfide-Appended siRNA Nanoeyedrops: Noninvasive Gene Therapy for Targeting Retinal Angiogenesis

  • ACS Nano. 2025 Oct 14;19(40):35333-35347. doi: 10.1021/acsnano.4c14313.
Shuya Liu 1,  Dongliang Wang 2,  Sishi Ye 3,  Junjie Zhang 1,  Beiyan Du 3,  Zhijie Lian 1,  Wen Yang 1,  Jie Zhou 4,  Qi Chen 5,  Juan Li 6,  Jingying Li 1 3,  Huanghao Yang 1 5
Affiliations

Affiliations

  • 1 New Cornerstone Science Laboratory, MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, Fuzhou 350108, P. R. China.
  • 2 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, SunYat-sen University, Guangzhou 510060, P. R. China.
  • 3 College of Biological Science and Engineering, Fuzhou University, Fuzhou 350108, P. R. China.
  • 4 Department of Bioengineering and Biopharmaceutics, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian 350122, P. R. China.
  • 5 College of medicine, Fuzhou University, Fuzhou 350108, P. R. China.
  • 6 Zhejiang Cancer Hospital, The Key Laboratory of Zhejiang Province for Aptamers and Theragnostic, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, P. R. China.
PMID: 41037347 DOI: 10.1021/acsnano.4c14313
Abstract

Given the significant advantages the eye presents as a target organ for gene therapy, it has remained at the forefront of translational research in this field. However, gene delivery to the desired tissue, particularly the retina, via a noninvasive route of administration poses a substantial physical challenge due to the presence of multiple ocular barriers. Here, we develop disulfide-appended small interfering RNA (DS-siRNA) Nanoeyedrops that target pathological retinal angiogenesis. These Nanoeyedrops enable noninvasive and effective gene delivery into the retina through the thiol-mediated uptake route. We have demonstrated that the thiol-mediated uptake route represents a powerful approach capable of overcoming ocular barriers. Ultimately, we have applied these Nanoeyedrops to deliver VEGF siRNA, which has exhibited substantial effects in both choroidal neovascularization and retinoblastoma mouse models. It serves as a highly efficient delivery system that enables noninvasive ocular gene delivery with high bioavailability, thereby offering a promising strategy for treating retinal diseases.

Keywords

Nanoeyedrops; ocular barrier; retinal disease; self-assembly; small interfering RNA; thiol−disulfide exchange.

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