Evidence map›Paper›PMID 40667189›Full record

ArticlebioRxiv : the preprint server for biology2025

Sustained Lysosomal Delivery of Enhanced Cy3-Labeled Acid Nanoparticles Restores Lysosomal pH in Retinal Pigment Epithelial Cells and Astrocytes.

Jiaqi Li, Tianchen Wang, Wennan Lu, Davit Jishkariani, Andrew Tsourkas, Simon Kaja, Rohini M Nair, Joshua L Dunaief, Claire H Mitchell

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

9 authors.

Jiaqi LiDepartment of Chemistry, School of Arts and Science, Health Sciences Campus, Maywood, IL, USA.
Tianchen WangDepartment of Chemistry, School of Arts and Science, Health Sciences Campus, Maywood, IL, USA.
Wennan LuDepartment of Basic and Translational Science, School of Dental Medicine.
Davit JishkarianiChemical and Nanoparticle Synthesis Core, University of Pennsylvania, Philadelphia, Pennsylvania, USA United States.
Andrew TsourkasChemical and Nanoparticle Synthesis Core, University of Pennsylvania, Philadelphia, Pennsylvania, USA United States.
Simon KajaOphthalmology and Molecular Pharmacology and Neuroscience, Loyola University Chicago, Health Sciences Campus, Maywood, IL, USA.
Rohini M NairDepartment of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA United States.
Joshua L DunaiefDepartment of Ophthalmology, University of Pennsylvania, Philadelphia, Pennsylvania, USA United States.
Claire H MitchellDepartment of Basic and Translational Science, School of Dental Medicine.

Funding

Purines and the Health of Retinal Ganglion CellsR01EY015537 · NEI · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, CLAIRE H · 2005 to 2023
$6.7M
REGULATION OF LYSOSOMAL PH IN RPE CELLSR01EY013434 · NEI · UNIVERSITY OF PENNSYLVANIA · PI MITCHELL, CLAIRE H · 2002 to 2020
$5.3M
NEI NIH HHS R01 EY013434NEI NIH HHS R01 EY015537
6 · The paper itself

Abstract

Lysosomal pH is frequently elevated in age-dependent neurodegenerations like Age-related Macular Degeneration (AMD), Alzheimer's Disease (AD), and Parkinson's Disease (PD). Tools that restore lysosomal pH to an optimal acidic range could enhance enzymatic degradation and reduce waste accumulation. Acidic nanoparticles offer a promising strategy for restoring lysosomal function, but accurate tracking of organelle delivery and long-term retention is needed to optimize dosage. To improve detection and enhance delivery, nanoparticles were synthesized from Poly(D,L-lactide-co-glycolide) (PLGA) polymers covalently linked to the fluorescent Cyanine3 amine (Cy3) probe. Nanoparticle concentration and loading times were optimized to achieve >90% delivery to lysosomes in cultured induced pluripotent stem cell-derived retinal pigment epithelial (iPS-RPE) cells. Uptake was heterogeneous, varying between adjacent cells. Once loaded into lysosomes, the nanoparticles were stably retained, with no detectable changes in concentration, distribution, or size for at least 28 days. iPS-RPE cells internalized more nanoparticles than the ARPE-19 cell line or mouse optic nerve head astrocyte cultures. Functionally, PLGA nanoparticles restored an acidic pH and cathepsin D levels in compromised lysosomes. In summary, Cy3-PLGA nanoparticles enabled improved tracking and long-term delivery to lysosomes, supporting future

Indexed as

age dependent neurodegenerationsautophagycathepsin DLysosomal pHnanoparticle labelingnanoparticle trafficking

Identifiers

PMID40667189
PMCPMC12262198

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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.