Reduction-responsive polymeric micelles for trans-corneal targeted delivery of microRNA-21-5p and glaucoma-specific gene therapy
Abstract
The therapeutic value of microRNA (miRNA) for the treatment of glaucoma has become a focus of attention. However, naked miRNA cannot cross the corneal barrier and reach the target tissue by itself. Thus, the precise transport of miRNA to the target sites is key to the success of gene therapy. Herein, we selected a miRNA, namely miR-21-5p, based on its unique intraocular pressure (IOP) mechano-sensing property. Moreover, a biocompatible polymeric poly(L-lysine) (PLL) micelle conjugated with collagenase and ABCA1 antibody was judiciously constructed to achieve the trans-corneal and target delivery of miR-21-5p to the trabecular meshwork (TM) and Schlemm's canal (SC) tissues inside the eye. The topically administrated PLL micelles as an eye drop successfully crossed the cornea with the help of collagenase and then preferentially accumulated in the target TM/SC tissues under the guidance of the ABCA1 antibody. When endocytosed by TM/SC cells, the PLL micelles could be decomposed in the reductive lysosomal environment to release miR-21-5p for successfully lowering the IOP by activating the miR-21-5p/eNOS/MMP9 signaling axis, which will open new prospects for glaucoma-specific gene therapy.
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Topically administered PLL micelles successfully penetrated the cornea aided by collagenase and preferentially accumulated within TM/SC tissue under ABCA1 antibody guidance.
“Topically administered PLL micelles successfully penetrated the cornea aided by collagenase and preferentially accumulated within TM/SC tissue under ABCA1 antibody guidance.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [162]
Upon endocytosis by TM/SC cells, PLL micelles could decompose within the reductive lysosomal environment to discharge miR-21-5p, which aimed at efficaciously lowering IOP through activation of the miR-21-5p/eNOS/MMP9 signaling axis.
“Upon endocytosis by TM/SC cells, the PLL micelles could decompose within the reductive lysosomal environment to discharge miR-21-5p, which aimed at efficaciously lowering IOP through the activation of miR-21-5p/eNOS/MMP9 signaling axis.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [162]
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From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics
Sun, M., Wang, J., Fan, W., Wang, K., Wang, Y., Zhang, J., Ding, S., Zhang, C., Feng, Z., Wang, Y.-G., et al. (2025) · Materials today. Bio · doi:10.1016/j.mtbio.2025.102537 · Cited by 7 · see citing works
“These biomaterials will open new avenues for glaucoma-specific gene therapy [162].”
Self-citation
- Authors
- Han, B., Zhang, R., Li, L., Hu, C., Li, M., Liu, J., Sun, X., Fan, W., Xie, J., & Lei, Y.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- China Pharmaceutical University (CN)
- Zhongda Hospital Southeast University (CN)
- Corresponding author
- Sun, Xinghuai
- Fan, Wenpei
- Xie, Jinbing
- Lei, Yuan
- Venue
- Journal of Materials Chemistry B
- Publisher
- Royal Society of Chemistry (RSC)
- Published
- 2023
- Volume
- 11
- Issue
- 43
- Pages
- 10433-10445
- ISSN
- 2050-750X (ISSN-L)
- 2050-7518
- OpenAlex
- W4387586900
- Cited by
- 11
- References
- 47
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 4
- FWCI
- 0.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Materials Chemistry B (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Science Foundation of Shanghai Municipality (21ZR1411500, 22ZR1409900)
- National Key Research and Development Program of China (2020YFA0112700)
- National Natural Science Foundation of China (82070959, 82172010, 82271082)
- Fudan University (yg2022-13)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Keywords
- polymeric micelles, miR-21-5p, glaucoma, poly-L-lysine, collagenase, reduction-responsive drug release, trabecular meshwork, Schlemm's canal, intraocular pressure, eye drops, gene therapy
- MeSH terms
- Cornea, Glaucoma, Humans, Micelles, Collagenases, MicroRNAs
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