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Targeted Delivery of Cell Softening Micelles to Schlemm's Canal Endothelial Cells for Treatment of Glaucoma.

Publication ,  Journal Article
Stack, T; Vincent, M; Vahabikashi, A; Li, G; Perkumas, KM; Stamer, WD; Johnson, M; Scott, E
Published in: Small
October 2020

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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Published In

Small

DOI

EISSN

1613-6829

Publication Date

October 2020

Volume

16

Issue

43

Start / End Page

e2004205

Location

Germany

Related Subject Headings

  • Nanoscience & Nanotechnology
  • Micelles
  • Mice
  • Glaucoma
  • Eye
  • Endothelial Cells
  • Aqueous Humor
  • Animals
 

Citation

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Stack, T., Vincent, M., Vahabikashi, A., Li, G., Perkumas, K. M., Stamer, W. D., … Scott, E. (2020). Targeted Delivery of Cell Softening Micelles to Schlemm's Canal Endothelial Cells for Treatment of Glaucoma. Small, 16(43), e2004205. https://doi.org/10.1002/smll.202004205
Stack, Trevor, Michael Vincent, Amir Vahabikashi, Guorong Li, Kristin M. Perkumas, W Daniel Stamer, Mark Johnson, and Evan Scott. “Targeted Delivery of Cell Softening Micelles to Schlemm's Canal Endothelial Cells for Treatment of Glaucoma.Small 16, no. 43 (October 2020): e2004205. https://doi.org/10.1002/smll.202004205.
Stack T, Vincent M, Vahabikashi A, Li G, Perkumas KM, Stamer WD, et al. Targeted Delivery of Cell Softening Micelles to Schlemm's Canal Endothelial Cells for Treatment of Glaucoma. Small. 2020 Oct;16(43):e2004205.
Stack, Trevor, et al. “Targeted Delivery of Cell Softening Micelles to Schlemm's Canal Endothelial Cells for Treatment of Glaucoma.Small, vol. 16, no. 43, Oct. 2020, p. e2004205. Pubmed, doi:10.1002/smll.202004205.
Stack T, Vincent M, Vahabikashi A, Li G, Perkumas KM, Stamer WD, Johnson M, Scott E. Targeted Delivery of Cell Softening Micelles to Schlemm's Canal Endothelial Cells for Treatment of Glaucoma. Small. 2020 Oct;16(43):e2004205.
Journal cover image

Published In

Small

DOI

EISSN

1613-6829

Publication Date

October 2020

Volume

16

Issue

43

Start / End Page

e2004205

Location

Germany

Related Subject Headings

  • Nanoscience & Nanotechnology
  • Micelles
  • Mice
  • Glaucoma
  • Eye
  • Endothelial Cells
  • Aqueous Humor
  • Animals