pH-Responsive polymer boosts cytosolic siRNA release for retinal neovascularization therapy
Open accessAbstract
Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.
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PACD/siRNA polyplexes showed remarkable intracellular endosomal escape efficiency, prominent gene silencing effects, and potent anti-angiogenesis impacts.
“Encouragingly, the PACD/siRNA polyplexes showed remarkable intracellular endosomal escape efficiency, prominent gene silencing effects, and potent anti-angiogenesis impacts.”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [171]
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- Authors
- Guo, S., Li, C., Wang, C., Cao, X., Liu, X., Liang, X.-J., Huang, Y., & Weng, Y.
- Affiliations
- Beijing Institute of Technology (CN)
- Binzhou Medical University (CN)
- Wenzhou Medical University (CN)
- Chinese Academy of Sciences (CN)
- Corresponding author
- Weng, Yuhua
- ORCID
- Venue
- Acta Pharmaceutica Sinica B
- Publisher
- Elsevier BV
- Published
- 2024-02
- Volume
- 14
- Issue
- 2
- Pages
- 781-794
- ISSN
- 2211-3835 (ISSN-L)
- PMC
- PMC10840400
- OpenAlex
- W4386573774
- Cited by
- 36
- References
- 27
- Citations by year
- 2026: 9 · 2025: 21 · 2024: 6
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Acta Pharmaceutica Sinica B (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Beijing Nova Program
- Beijing Municipal Science and Technology Commission, Adminitrative Commission of Zhongguancun Science Park (20220484207)
- National Key Research and Development Program of China (2021YFA1201000, 2021YFC2302400, 2021YFE0106900)
- Wenzhou Medical University
- Fundamental Research Funds for the Central Universities (2022CX01013)
- National Natural Science Foundation of China (31901053, 32001008, 32101148, 32101157, 32171394, 82202338)
- Beijing Institute of Technology
- 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
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- siRNA delivery, retinal neovascularization, pH-responsive polymers, polymeric micelles, polyplexes, endosomal escape, ocular drug delivery, angiogenesis inhibition, hypoxia-induced angiogenesis, gene silencing
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