Evidence map›Paper›PMID 32630415›Full record

ArticlePharmaceutics2020

Targeting Activated Hepatic Stellate Cells Using Collagen-Binding Chitosan Nanoparticles for siRNA Delivery to Fibrotic Livers.

Menna Azzam, Sara El Safy, Sarah A Abdelgelil, Ralf Weiskirchen, Anastasia Asimakopoulou, Federica de Lorenzi, Twan Lammers, Samar Mansour, Salma Tammam

Open access · goldAbstract read
In one paragraph

Article in Pharmaceutics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.5field-weighted citation impact, top 9% of its field
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

17 citing papers in PubMed, 39 citations in OpenAlex.

  1. Tissue-specific gene delivery approaches.Bioengineering & translational medicine · 2026
    Review
  2. Review
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  4. Article
  5. Article
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  8. Article
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  10. The landscape of nanoparticle-based siRNA delivery and therapeutic development.Molecular therapy : the journal of the American Society of Gene Therapy · 2024
    Review
  11. Article
  12. Article
  13. Nanoparticles and cytokine response.Frontiers in bioengineering and biotechnology · 2023
    Review
  14. Review
  15. Article
  16. Article
  17. Repurpose but also (nano)-reformulate! The potential role of nanomedicine in the battle against SARS-CoV2.Journal of controlled release : official journal of the Controlled Release Society · 2021
    Review
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 at 2 institutions in 2 countries.

Menna AzzamDepartment of Pharmaceutical Technology, Faculty of Pharmacy & Biotechnology, The German University in Cairo (GUC), 11835 Cairo, Egypt.
Sara El SafyDepartment of Pharmaceutical Technology, Faculty of Pharmacy & Biotechnology, The German University in Cairo (GUC), 11835 Cairo, Egypt.
Sarah A AbdelgelilDepartment of Pharmaceutical Technology, Faculty of Pharmacy & Biotechnology, The German University in Cairo (GUC), 11835 Cairo, Egypt.
Ralf WeiskirchenInstitute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital, D-52074 Aachen, Germany.ORCID 0000-0003-3888-0931
Anastasia AsimakopoulouInstitute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital, D-52074 Aachen, Germany.
Federica de LorenziDepartment of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, D-52074 Aachen, Germany.
Twan LammersDepartment of Nanomedicine and Theranostics, Institute for Experimental Molecular Imaging, RWTH Aachen University Clinic, D-52074 Aachen, Germany.
Samar MansourDepartment of Pharmaceutical Technology, Faculty of Pharmacy & Biotechnology, The German University in Cairo (GUC), 11835 Cairo, Egypt.
Salma TammamDepartment of Pharmaceutical Technology, Faculty of Pharmacy & Biotechnology, The German University in Cairo (GUC), 11835 Cairo, Egypt.
German University in Cairo · EGRWTH Aachen University · DE

Funding

Aachen Interdisciplinary Center for Clinical Research NADeutsche Forschungsgemeinschaft DFG: SFB/TRR57, SFB1066 and GRK2375 (#331065168)Deutscher Akademischer Austausch Dienst Kairo NA
6 · The paper itself

Abstract

Activated hepatic stellate cells (aHSCs) are the main orchestrators of the fibrotic cascade in inflamed livers, with transforming growth factor-beta (TGF-β) being the most potent pro-fibrotic cytokine. Hence, aHSCs serve as interesting therapeutic targets. However, drug delivery to aHSCs is hindered by excessive collagen deposition in the extracellular matrix (ECM) and capillarization of liver sinusoids. Chitosan-nanoparticles (CS-NPs) show intrinsic affinity for collagen, holding potential for drug delivery to fibrotic livers. Here, we employed CS-NPs for anti-TGF-β siRNA delivery, promoting delivery into aHSCs via modification with platelet-derived growth factor receptor-beta binding peptides. In-vitro experiments using aHSCs demonstrated the association of unmodified CS-NPs to the collagen-rich ECM, with reduced intracellular accumulation. Peptide-modified CS-NPs showed a higher propensity to localize intracellularly; however, this was only the case upon ECM-collagen reduction via collagenase treatment. Peptide-modified CS-NPs were more potent than unmodified CS-NPs in reducing TGF-β expression, implying that while collagen binding promotes liver accumulation, it hinders cell-specific siRNA delivery. In-vivo, CS-NPs successfully accumulated in fibrotic livers via collagen binding. Similar to in-vitro findings, when mice were pretreated with collagenase-loaded CS-NPs, the accumulation of peptide-modified NPs increased. Our findings demonstrate the usefulness of NPs modification with targeting ligands and collagenase treatment for aHSCs targeting and highlight the importance of chitosan-collagen binding in drug delivery to fibrotic diseases.

Indexed as

activated hepatic stellate cellsactive targetingchitosan nanoparticlescollagencollagenaseliver fibrosissiRNA deliveryTGF-β

Identifiers

PMID32630415
PMCPMC7356502
OpenAlexW3037261121

What OpenQuestion holds

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LicenceCC BY
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.