Evidence map›Paper›PMID 42576929›Full record

ArticleMaterials today. Bio2026

Supramolecular Nrf2-activating peptide nanotherapeutics enable deep retinal penetration and RPE targeting for dry age-related macular degeneration.

Zihan Zheng, Guangyu Rong, Gengji Li, Yujiao Zhai, Yu Liang, Mingsu Shi, Jiaqiu Huang, Yihan Zhang, Xinyi Zhao, Qiao Zhuo and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Materials today. Bio, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Zihan ZhengEye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Guangyu RongEye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Gengji LiEye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Yujiao ZhaiFrontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Yu LiangEye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Mingsu ShiEye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Jiaqiu HuangEye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Yihan ZhangEye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Xinyi ZhaoEye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Qiao ZhuoEye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Jiaxu HongEye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Weiyi XiaEye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Yiyun ChengFrontiers Science Center of Genome Editing and Cell Therapy, Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai, 200241, China.
Chen ZhaoEye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dry age-related macular degeneration (AMD) is a leading cause of blindness that currently lacks effective therapies. Restoring redox homeostasis in the retinal pigment epithelium (RPE) via the Keap1-Nrf2 axis offers a compelling precise therapeutic strategy. While peptide-based protein-protein interaction (PPI) inhibitors are highly specific for this axis, the delivery to the deep RPE layer remains a formidable challenge, typically restricted by electrostatic entrapment within the vitreous matrix or limited transretinal penetration. Herein, we developed a novel, mechanism-driven, supramolecular peptide nanotherapeutic (FNBP) engineered to bypass these barriers and reach the RPE layer. Driven by distinct fluorophilic self-assembly, FNBP spontaneously organizes into bio-inert nanostructures that evade vitreous adhesion and exhibit superior transretinal diffusivity and accumulation to the RPE layer. Upon RPE internalization, the assembly leverages its physicochemical properties to trigger efficient cytosolic release, allowing the payload to disrupt the Keap1-Nrf2 interaction, thereby enabling potent Nrf2 activation and restoring redox homeostasis. In a murine model of retinal degeneration, a single intravitreal injection provided sustained preservation of retinal integrity for 28 days, significantly outperforming conventional peptide formulations and clinical supplements. This work offers a precise, mechanism-based solution for RPE-targeted regulation therapies and establishes a paradigm for designing peptide nanotherapeutics that circumvent the intrinsic limitations of retinal drug delivery.

Indexed as

Deep retinal penetrationDry age-related macular degenerationFluoroalkylationKeap1/Nrf2 pathwayPeptide deliveryRPE targeting

Identifiers

PMID42576929
PMCPMC13453495

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.