Targeted delivery of cell softening micelles to schlemm's canal endothelial cells for treatment of glaucoma
Open accessAbstract
Increased stiffness of the Schlemm's canal (SC) endothelium in the aqueous humor outflow pathways has been associated with elevated intraocular pressure (IOP) in glaucoma. Novel treatments that relax this endothelium, such as actin depolymerizers and rho kinase inhibitors, are in development. Unfortunately, these treatments have undesirable off-target effects and a lower than desired potency. To address these issues, a targeted PEG-b-PPS micelle loaded with actin depolymerizer latrunculin A (tLatA-MC) is developed. Targeting of SC cells is achieved by modifying the micelle surface with a high affinity peptide that binds the VEGFR3/FLT4 receptor, a lymphatic lineage marker found to be highly expressed by SC cells relative to other ocular cells. During in vitro optimization, increasing the peptide surface density increased micellar uptake in SC cells while unexpectedly decreasing uptake by human umbilical vein endothelial cells (HUVEC). The functional efficacy of tLatA-MC, as measured by decreased SC cell stiffness compared to non-targeted micelles (ntLatA-MC) or targeted blank micelles (tBL-MC), is verified using atomic force microscopy. tLatA-MC reduced IOP in an in vivo mouse model by 30-50%. The results validate the use of a cell-softening nanotherapy to selectively modulate stiffness of SC cells for therapeutic reduction of IOP and treatment of glaucoma.
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A single dose of tLatA-MC achieved a rapid and substantial reduction in IOP by 30-50% in a mouse model, effectively normalizing pressure within 4 h and sustaining the effect for up to 24 h.
“Notably, a single dose of tLatA-MC achieved a rapid and substantial reduction in IOP by 30–50 % in a mouse model, effectively normalizing the pressure within 4 h of administration and sustaining the effect for up to 24 h.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [161]
The section “tLatA-MC reduces IOP in C57Bl6 mice” (page unavailable) reports 30–49% lower IOP than comparator micelles at 24 hours after injection. Our copy does not report pressure normalization within 4 hours or establish when the reduction began, so the claimed rapid onset and sustained effect from 4 to 24 hours are unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe results validate tLatA-MC utilization as a cell-softening nanotherapy to selectively regulate SC cell stiffness for IOP reduction and glaucoma management.
“The results validate its utilization as a cell-softening nanotherapy to selectively regulate SC cell stiffness for IOP reduction and glaucoma management [161]”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [161]
Modification of PEG-b-PPS with specific targeted peptides could effectively target SC cells and increase their uptake, which is a neoteric strategy for the management of glaucoma.
“It reported that the modification of PEG-b-PPS with specific targeted peptides could effectively target SC cells and increase their uptake, which is a neoteric strategy for the management of glaucoma [161].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [161]
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- Authors
- Stack, T., Vincent, M., Vahabikashi, A., Li, G., Perkumas, K. M., Stamer, W. D., Johnson, M., & Scott, E.
- Affiliations
- Northwestern University (US)
- Duke University (US)
- Corresponding author
- Scott, Evan
- Venue
- Small
- Publisher
- Wiley
- Published
- 2020-10
- Volume
- 16
- Issue
- 43
- Pages
- e2004205-e2004205
- ISSN
- 1613-6810 (ISSN-L)
- 1613-6829
- PMC
- PMC7647937
- OpenAlex
- W3090501045
- Cited by
- 37
- References
- 36
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 4 · 2023: 4 · 2022: 5 · 2021: 11
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Small (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1R01EY019696, 1R0EY022359)
- Topics
- Health Sciences › Medicine › Ophthalmology › Glaucoma and retinal disorders
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- glaucoma, Schlemm's canal endothelial cells, cell softening, micelles, latrunculin A, actin depolymerization, peptide surface modification, targeted drug delivery, intraocular pressure, endothelial stiffness, aqueous humor outflow, nanotherapy
- MeSH terms
- Animals, Aqueous Humor, Eye, Glaucoma, Micelles, Endothelial Cells, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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