Research Article

Effective treatment of retinal neovascular leakage with fusogenic porous silicon nanoparticles delivering VEGF-siRNA

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Department of Chemistry & Biochemistry, University of California, San Diego, CA 92093, USA

Department of Ophthalmology, Jacobs Retinal Center at Shiley Eye Institute, University of California, San Diego, CA 92093, USA

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Ella Jiyoon Lee

Department of Chemistry & Biochemistry, University of California, San Diego, CA 92093, USA

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Melina Cavichini

Department of Ophthalmology, Jacobs Retinal Center at Shiley Eye Institute, University of California, San Diego, CA 92093, USA

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Alexandra Warter

Department of Ophthalmology, Jacobs Retinal Center at Shiley Eye Institute, University of California, San Diego, CA 92093, USA

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Fritz Gerald P Kalaw

Department of Ophthalmology, Jacobs Retinal Center at Shiley Eye Institute, University of California, San Diego, CA 92093, USA

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Anna Heinke

Department of Ophthalmology, Jacobs Retinal Center at Shiley Eye Institute, University of California, San Diego, CA 92093, USA

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Ruhan Fan

Materials Science & Engineering, University of California, San Diego, CA 92093, USA

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Lingyun Cheng

Department of Ophthalmology, Jacobs Retinal Center at Shiley Eye Institute, University of California, San Diego, CA 92093, USA

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Michael J Sailor

Department of Chemistry & Biochemistry, University of California, San Diego, CA 92093, USA

Materials Science & Engineering, University of California, San Diego, CA 92093, USA

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William R Freeman

Department of Ophthalmology, Jacobs Retinal Center at Shiley Eye Institute, University of California, San Diego, CA 92093, USA

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Published Online:7 Feb 2023https://doi.org/10.2217/nnm-2022-0255

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Abstract

Aim: To evaluate an intravitreally injected nanoparticle platform designed to deliver VEGF-A siRNA to inhibit retinal neovascular leakage as a new treatment for proliferative diabetic retinopathy and diabetic macular edema. Materials & methods: Fusogenic lipid-coated porous silicon nanoparticles loaded with VEGF-A siRNA, and pendant neovascular integrin-homing iRGD, were evaluated for efficacy by intravitreal injection in a rabbit model of retinal neovascularization. Results: For 12 weeks post-treatment, a reduction in vascular leakage was observed for treated diseased eyes versus control eyes (p = 0.0137), with a corresponding reduction in vitreous VEGF-A. Conclusion: Fusogenic lipid-coated porous silicon nanoparticles siRNA delivery provides persistent knockdown of VEGF-A and reduced leakage in a rabbit model of retinal neovascularization as a potential new intraocular therapeutic.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

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Vol. 17, No. 27

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History

Received 30 September 2022

Accepted 13 January 2023

Published online 7 February 2023

Published in print November 2022

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/nnm-2022-0255

Acknowledgments

We would like to thank J Carroll for running the fluorescein angiography imaging camera and D-U Bartsch for discussions on fluorescein angiography image analysis.

Financial & competing interests disclosure

This project has been funded in part by a grant from the Joan and Irwin Jacobs Family Fellowship Fund, unrestricted Jacobs Retina Center Grant, the National Institutes of Health (NIH) grant no. R01 EY033847-01 WRF, NIH core grant no. P30EY022589, NIH grant no. R01 EY016323 DUB and an unrestricted grant from Research to Prevent Blindness, NY WRF. Additional support was received from National Science Foundation (NSF) through the UC San Diego Materials Research Science and Engineering Center (UCSD MRSEC) DMR-2011924. This work was performed in part at the San Diego Nanotechnology Infrastructure of UCSD, a member of the National Nanotechnology Coordinated Infrastructure, which is supported by the National Science Foundation, grant no. ECCS-1542148. Additional facilities and instrumentation were supported by NSF through the UCSD MRSEC, grant no. DMR-2011924. JF Grondek thanks the University of California, San Diego for a Chancellor's Interdisciplinary Collaboratories fellowship. L Cheng has a financial interest as scientific advisor and shareholder with Spinnaker Biosceinces, Inc. WR Freeman has an equity interest and a financial interest as a shareholder, scientific advisor and board member with Spinnaker Biosceinces, Inc. MJ Sailor is a scientific founder, a member of the board of directors, and he holds an equity interest of Spinnaker Biosciences and Cend Therapeutics. He also has a financial interest (as a consultant, shareholder, scientific advisor and/or board member) with Bejing ITEC Technologies, Illumina, Matrix Technologies, Pacific Integrated Energy, TruTag Technologies and Well-Healthcare Technologies. MJ Sailor is a Guest Professor at Zhejiang University, China. Although one or more of the grants that supported this research has been identified for conflict-of-interest management based on the overall scope of the project and its potential benefit to one or more of these companies, the research findings included in this particular publication may not necessarily relate to their interests. The terms of this arrangement have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All animal studies were performed using New Zealand pigmented rabbits, which were treated in accordance with the University of California, San Diego, American Association for Laboratory Animal Science the Institutional Animal Care and Use Committee (IACUC) standards of practice, and in accordance with the Association for Research in Vision and Ophthalmology statement for the use of animals in ophthalmic and vision research.

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