Evidence map›Paper›PMID 39289695›Full record

ArticleFluids and barriers of the CNS2024

Truncated mini LRP1 transports cargo from luminal to basolateral side across the blood brain barrier.

Laura Fritzen, Katharina Wienken, Lelia Wagner, Magdalena Kurtyka, Katharina Vogel, Jakob Körbelin, Sascha Weggen, Gert Fricker, Claus U Pietrzik

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In one paragraph

Article in Fluids and barriers of the CNS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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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

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3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Laura FritzenMolecular Neurodegeneration, Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University of Mainz, Duesbergweg 6, 55099, Mainz, Germany. fritzenl@uni-mainz.de.ORCID https://orcid.org/0000-0002-2094-6368
Katharina WienkenInstitute for Pharmacy and Molecular Biotechnology, University Heidelberg, Heidelberg, Germany.
Lelia WagnerInstitute for Pharmacy and Molecular Biotechnology, University Heidelberg, Heidelberg, Germany.
Magdalena KurtykaMolecular Neurodegeneration, Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University of Mainz, Duesbergweg 6, 55099, Mainz, Germany.
Katharina VogelDepartment of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany.
Jakob KörbelinDepartment for Oncology and Hematology, University Medical Center Hamburg-Eppendorf, Hubertus Wald Cancer Center, Hamburg, Germany.
Sascha WeggenDepartment of Neuropathology, Heinrich-Heine-University, Düsseldorf, Germany.
Gert FrickerInstitute for Pharmacy and Molecular Biotechnology, University Heidelberg, Heidelberg, Germany.
Claus U PietrzikMolecular Neurodegeneration, Institute for Pathobiochemistry, University Medical Center of the Johannes Gutenberg-University of Mainz, Duesbergweg 6, 55099, Mainz, Germany. pietrzik@uni-mainz.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe most crucial area to focus on when thinking of novel pathways for drug delivery into the CNS is the blood brain barrier (BBB). A number of nanoparticulate formulations have been shown in earlier research to target receptors at the BBB and transport therapeutics into the CNS. However, no mechanism for CNS entrance and movement throughout the CNS parenchyma has been proposed yet. Here, the truncated mini low-density lipoprotein receptor-related protein 1 mLRP1_DIV* was presented as blood to brain transport carrier, exemplified by antibodies and immunoliposomes using a systematic approach to screen the receptor and its ligands' route across endothelial cells in vitro.

methodsThe use of mLRP1_DIV* as liposomal carrier into the CNS was validated based on internalization and transport assays across an in vitro model of the BBB using hcMEC/D3 and bEnd.3 cells. Trafficking routes of mLRP1_DIV* and corresponding cargo across endothelial cells were analyzed using immunofluorescence. Modulation of γ-secretase activity by immunoliposomes loaded with the γ-secretase modulator BB25 was investigated in co-cultures of bEnd.3 mLRP1_DIV* cells and CHO cells overexpressing human amyloid precursor protein (APP) and presenilin 1 (PSEN1).

resultsWe showed that while expressed in vitro, mLRP1_DIV* transports both, antibodies and functionalized immunoliposomes from luminal to basolateral side across an in vitro model of the BBB, followed by their mLRP1_DIV* dependent release of the cargo. Importantly, functionalized liposomes loaded with the γ-secretase modulator BB25 were demonstrated to effectively reduce toxic Aß

conclusionTogether, the data strongly suggest mLRP1_DIV* as a promising tool for drug delivery into the CNS, as it allows a straight transport of cargo from luminal to abluminal side across an endothelial monolayer and it's release into brain parenchyma in vitro, where it exhibits its intended therapeutic effect.

Indexed as

Blood-Brain BarrierCricetulusLow Density Lipoprotein Receptor-Related Protein-1Amyloid Precursor Protein SecretasesAnimalsBiological TransportCHO CellsCoculture TechniquesEndothelial CellsHumansLiposomesMiceProtein TransportAmyloid Precursor Protein SecretasesLiposomesLow Density Lipoprotein Receptor-Related Protein-1LRP1 protein, humanBlood-brain barrier (BBB)Drug deliveryLiposomesLow-density lipoprotein receptor-related protein 1 (LRP1)Nanocarrierγ-secretase modulator (GSM)

Identifiers

PMID39289695
PMCPMC11409491

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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.