Evidence map›Paper›PMID 41773824›Full record

ArticleACS biomaterials science & engineering2026

AAV9-Mimetic Peptides and Electroporation Synergistically Enhance Nanoparticle Transport through the Blood-Brain Barrier.

Nina Butkovich, Yifei Xu, Yuchen Song, Lu Wang, Aaron Ramirez, Enya Li, Nikhil Tien Chi Siao, Eric Velazquez-Rivera, Liangzhong Xiang, Xiangmin Xu and 1 more

Abstract read
In one paragraph

Article in ACS biomaterials science & engineering, 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

11 authors.

Nina ButkovichDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, California 92697, United States.
Yifei XuDepartment of Biomedical Engineering, University of California, Irvine, California 92697, United States.
Yuchen SongDepartment of Biomedical Engineering, University of California, Irvine, California 92697, United States.
Lu WangDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, California 92697, United States.
Aaron RamirezDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, California 92697, United States.
Enya LiDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, California 92697, United States.
Nikhil Tien Chi SiaoDepartment of Biomedical Engineering, University of California, Irvine, California 92697, United States.
Eric Velazquez-RiveraDepartment of Anatomy and Neurobiology, University of California, Irvine, California 92697, United States.
Liangzhong XiangDepartment of Biomedical Engineering, University of California, Irvine, California 92697, United States.
Xiangmin XuDepartment of Biomedical Engineering, University of California, Irvine, California 92697, United States.
Szu-Wen WangDepartment of Chemical and Biomolecular Engineering, University of California, Irvine, California 92697, United States.ORCID 0000-0001-7398-0220

Funding

UC Irvine Center for the production and distribution of cell-type-specific viral targeting reagentsU24MH133236 · NIMH · UNIVERSITY OF CALIFORNIA-IRVINE · PI FISHELL, GORDON J, XU, XIANGMIN · 2023 to 2025
$3.6M
Enhancer AAV-based genetic access and manipulation of specific brain cell types implicated in aging and Alzheimer's DiseaseR61AG094609 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI XU, XIANGMIN · 2025 to 2025
$2.2M
The UC Irvine Center for Neural Circuit Mapping training program in Alzheimer's disease researchT32AG081185 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI Todd C Holmes, XIANGMIN XU · 2024 to 2026
$833k
NIA NIH HHS R61 AG094609NIA NIH HHS T32 AG081185NIMH NIH HHS U24 MH133236
6 · The paper itself

Abstract

Crossing the blood-brain barrier (BBB) remains a major hurdle in neurotherapeutics delivery. However, adeno-associated virus serotype 9 (AAV9) variants can cross from the bloodstream to accumulate in brain tissue, with their tropism facilitated by surface peptide loops. In this work, we examined the feasibility of grafting AAV9-based peptides (AAV.PHP.eB, AAV.X1, and AAV.CPP.16) onto nanoparticles (NPs) to increase transport through brain endothelial cells. We also evaluated the effects of combining the cell-mediated transcytosis strategy with nanosecond pulsed electric fields (nsPEFs). To test the importance of the AAV9-mimetic peptide structural presentation, we chemically conjugated linear peptides or recombinantly inserted peptides into external loops of a protein NP delivery scaffold (E2). E2 shares similar size, symmetry, and nanostructure features to AAV9 but is based on a non-viral source. Computational modeling, particle sizes, and circular dichroism data showed that NPs were folded and intact, even after peptide insertion. NP uptake by brain endothelial cells was 6.2- and 3.4-fold greater (after 4 h) for designs that integrated AAV.X1 or AAV.CPP.16 loop peptides into the NP, relative to chemical conjugation of their respective linear peptides; this highlights the importance of retaining the structural context of the AAV9-derived peptide loops. Using a transwell BBB assay which was optimized to be conducted with nsPEF, we showed that the highest transcellular passage of NPs through the endothelial monolayer was obtained by combining the dual delivery strategies of AAV9 peptide loop incorporation and treatment with nsPEFs. This study also determined the AAV.CPP.16 loop to be the most effective peptide, with E2 NP transport to the basolateral side to be almost twice that of the AAV.X1 peptide in E2 (with nsPEFs). These results support the integration of AAV9-mimetic peptides into biomolecules and drug delivery carriers to facilitate their passage through the BBB.

Indexed as

Blood-Brain BarrierDependovirusElectroporationNanoparticlesPeptidesAnimalsBiological TransportEndothelial CellsHumansPeptidesAAV9blood−brain barriernanoparticlesprotein nanoparticlessurface peptides

Identifiers

PMID41773824
PMCPMC13179674

What OpenQuestion holds

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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.