Dual DNAzyme-loaded Treg-derived extracellular vesicles for targeted ocular delivery in diabetic retinopathy

  • Int J Pharm. 2026 Jun 25:701:127129. doi: 10.1016/j.ijpharm.2026.127129.
Yupeng Zhang  1 ,  Tong Wang  1 ,  Jian Cao  1 ,  Zhen Xing  2 ,  Jing Li  1 ,  Zixia Wu  1 ,  Ke Xiao  1 ,  Kangcheng Liu  1 ,  Zhipeng You  3
Affiliations
  • 1. The Affiliated Eye Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; Jiangxi Province Key Laboratory of Ophthalmology and Vision Sciences, Nanchang 330006, China; Jiangxi Clinical Research Center for Ophthalmic Disease, Nanchang 330006, China; Jiangxi Provincial Key Laboratory of Vitreoretinal Diseases for Health, Nanchang 330006, China.
  • 2. The Affiliated Hospital of Southwest Medical University, Sichuan 646000, China.
  • 3. The Affiliated Eye Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; Jiangxi Province Key Laboratory of Ophthalmology and Vision Sciences, Nanchang 330006, China; Jiangxi Clinical Research Center for Ophthalmic Disease, Nanchang 330006, China; Jiangxi Provincial Key Laboratory of Vitreoretinal Diseases for Health, Nanchang 330006, China. Electronic address: [email protected].
PMID: 42331118 DOI: 10.1016/j.ijpharm.2026.127129
Abstract

Diabetic retinopathy (DR) is one of the leading causes of preventable blindness worldwide. Current treatments, primarily based on anti-VEGF therapy, often require frequent intravitreal injections and have limited long-term efficacy. Ocular drug delivery with sustained release and stability remains a significant challenge. In this study, we developed a Treg-derived extracellular vesicle (EV) system loaded with dual DNAzymes for targeted ocular delivery in the treatment of DR. We evaluated the efficacy, safety, and stability of this delivery system both in vitro and in vivo. Our results demonstrated that the Treg-EV-loaded dual DNAzyme system effectively targeted the ocular vasculature, achieved sustained inhibition of VEGF and VEGFR2 expression, and significantly reduced retinal inflammation. Additionally, the system showed prolonged retinal retention and favorable safety profiles. This study presents a novel approach for DR treatment, providing a promising therapeutic strategy that could reduce the frequency of intravitreal injections and improve treatment outcomes. The Treg-EV-based delivery system holds great potential for clinical application in managing DR and improving patient outcomes.

Keywords
Anti-inflammatory therapy; DNAzyme; Diabetic retinopathy; Regulatory T cell-derived extracellular vesicles; VEGFA; VEGFR2.
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