Evidence map›Paper›PMID 41950645›Full record

ArticleBiomaterials2026

Human blood-brain barrier tissue model to characterize lipid nanoparticle delivery and transport mechanisms.

Xiaohan Zhang, Zhongfeng Ye, Shangyuan Cui, Taisia Shmushkovich, Hiroaki Tani, Ying Chen, Marly Coe, Artem Arkhangelskiy, Mariah L Arral, Maria G Savvidou and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

22 authors.

Xiaohan ZhangDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA; Eli Lilly and Company, Indianapolis, USA.
Zhongfeng YeDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Shangyuan CuiDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Taisia ShmushkovichEli Lilly and Company, Indianapolis, USA.
Hiroaki TaniEli Lilly and Company, Indianapolis, USA.
Ying ChenDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Marly CoeDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Artem ArkhangelskiyDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Mariah L ArralDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Maria G SavvidouDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Liam PowerDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Lihan LiuDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Yuchen ZhaoDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Julia HowellEli Lilly and Company, Indianapolis, USA.
Xingyan LiuEli Lilly and Company, Indianapolis, USA.
Evan C MarcetDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Seok-Man HoEli Lilly and Company, Indianapolis, USA.
Zhefu QueEli Lilly and Company, Indianapolis, USA.
Glenn LeungDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Adam S MullisDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA.
Qiaobing XuDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA. Electronic address: qiaobing.xu@tufts.edu.
David L KaplanDepartment of Biomedical Engineering, Tufts University, Medford, MA, 02155, USA. Electronic address: david.kaplan@tufts.edu.

Funding

Tissue Engineering Resource Center: TTDP41EB027062 · NIBIB · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Gordana Vunjak-Novakovic · 2019 to 2026
$12.6M
Tufts IRACDAK12GM133314 · NIGMS · TUFTS UNIVERSITY BOSTON · PI CLAIRE L MOORE, Jamie Lynn Maguire · 2019 to 2026
$8.4M
Develop lung-targeted synthetic lipid nanoparticles for mRNA medicine treating pulmonary lymphangioleiomyomatosisR01HL171728 · NHLBI · TUFTS UNIVERSITY MEDFORD · PI Yan Tang, Qiaobing Xu · 2024 to 2026
$1.9M
NHLBI NIH HHS R01 HL171728NIBIB NIH HHS P41 EB027062NIGMS NIH HHS K12 GM133314
6 · The paper itself

Abstract

Crossing the blood-brain barrier (BBB) to deliver lipid nanoparticles (LNPs) for central nervous system (CNS) therapies remains a major challenge. Here, we present a compartmentalized, human-derived 3D BBB tissue model incorporating five cell types, integrating a BBB with a protein composite scaffold system, to support parenchymal elements within a single integrated brain tissue system. This tissue model recapitulates key structural and functional features of the native human BBB, including enhanced tight junction formation, neuronal maturation, polarized endothelial morphology, low permeability, and a more homeostatic microenvironment. The silk-collagen composite provided physiologically relevant extracellular matrix stiffness that supported long-term culture stability and parenchymal development. Translational utility for evaluating CNS-penetrating LNPs was demonstrated by showing that LNP transport efficiency and parenchyma penetration capability in vitro correlated with in vivo brain delivery following systemic administration in mice. Furthermore, this in vitro tissue model enables mechanistic investigation of LNP transport via receptor modulation using siRNA knockdown and pharmacological inhibition, revealing scavenger receptor class B type I (SR-B1) and insulin receptor (INSR) as key mediators of receptor-dependent transcytosis. By enabling the integrated assessment of permeability, transport mechanisms, and toxicity within a single human-relevant in vitro tissue platform, this model serves as a tool to bridge the translational gap between LNP design, in vitro screening, and in vivo validation, to support the optimization of CNS drug delivery. Among the tested formulations, LNP1 exhibited superior BBB penetration, neuronal transfection, and low toxicity, highlighting its potential as a promising lead candidate for CNS mRNA therapeutics for neurological diseases.

Indexed as

Blood-Brain BarrierLipidsModels, BiologicalNanoparticlesAnimalsBiological TransportDrug Delivery SystemsHumansLiposomesMiceLipid NanoparticlesLipidsLiposomes3D human tissue modelBlood–brain barrierCNS drug deliveryLipid nanoparticlesTranslational model

Identifiers

PMID41950645
PMCPMC13488598

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.