Evidence map›Paper›PMID 31612183›Full record

ArticleNanoscale2019

Engineered nanoparticles for systemic siRNA delivery to malignant brain tumours.

Johan Karlsson, Yuan Rui, Kristen L Kozielski, Amanda L Placone, Olivia Choi, Stephany Y Tzeng, Jayoung Kim, Jamal J Keyes, Max I Bogorad, Kathleen Gabrielson and 4 more

Abstract read
In one paragraph

Article in Nanoscale, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing 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

31 citing papers in PubMed.

  1. Review
  2. Article
  3. Polymeric nanocarriers for therapeutic gene delivery.Asian journal of pharmaceutical sciences · 2025
    Review
  4. Review
  5. Article
  6. Review
  7. Article
  8. Review
  9. Review
  10. Article
  11. Biodegradable lipophilic polymeric mRNA nanoparticles for ligand-free targeting of splenic dendritic cells for cancer vaccination.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  12. Article
  13. Review
  14. Nucleic acid drug vectors for diagnosis and treatment of brain diseases.Signal transduction and targeted therapy · 2023
    Review
  15. Review
  16. Review
  17. Review
  18. Article
  19. Article
  20. 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

14 authors.

Johan KarlssonDepartment of Biomedical Engineering and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. green@jhu.edu and Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21218, USA. searson@jhu.edu and Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Yuan RuiDepartment of Biomedical Engineering and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. green@jhu.edu and Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21218, USA. searson@jhu.edu.
Kristen L KozielskiDepartment of Biomedical Engineering and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. green@jhu.edu and Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21218, USA. searson@jhu.edu.
Amanda L PlaconeInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21218, USA. searson@jhu.edu and Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Olivia ChoiDepartment of Biomedical Engineering and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. green@jhu.edu and Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21218, USA. searson@jhu.edu.
Stephany Y TzengDepartment of Biomedical Engineering and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. green@jhu.edu and Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21218, USA. searson@jhu.edu.
Jayoung KimDepartment of Biomedical Engineering and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. green@jhu.edu and Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21218, USA. searson@jhu.edu.
Jamal J KeyesDepartment of Biomedical Engineering and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. green@jhu.edu and Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21218, USA. searson@jhu.edu.
Max I BogoradInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21218, USA. searson@jhu.edu and Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Kathleen GabrielsonDepartment of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Hugo Guerrero-CazaresDepartment of Neurosurgery, Mayo Clinic Florida, Jacksonville, FL 32224, USA.
Alfredo Quiñones-HinojosaDepartment of Neurosurgery, Mayo Clinic Florida, Jacksonville, FL 32224, USA.
Peter C SearsonInstitute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21218, USA. searson@jhu.edu and Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.ORCID http://orcid.org/0000-0002-5417-0828
Jordan J GreenDepartment of Biomedical Engineering and the Translational Tissue Engineering Center, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA. green@jhu.edu and Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21218, USA. searson@jhu.edu and Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA and Departments of Neurosurgery, Oncology, and Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA and Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21231, USA and Sidney Kimmel Comprehensive Cancer Center and the Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.ORCID http://orcid.org/0000-0003-4176-3808

Funding

Nanoparticle Modified Human Fat Derived Mesenchymal Stem Cells for Brain Cancer (Change of Organization Application)R01CA195503 · NCI · MAYO CLINIC JACKSONVILLE · PI GREEN, JORDAN, QUINONES-HINOJOSA, ALFREDO · 2016 to 2020
$1.9M
BMP4 Engineered Mesenchymal Stem Cell Therapy for GlioblastomaR01CA183827 · NCI · MAYO CLINIC JACKSONVILLE · PI QUINONES-HINOJOSA, ALFREDO · 2015 to 2019
$1.9M
Gene Delivery Nanoparticles to Treat GlioblastomaR01CA228133 · NCI · JOHNS HOPKINS UNIVERSITY · PI GREEN, JORDAN · 2019 to 2023
$1.9M
Cancer-specific nanoparticle-mediated gene therapy to treat hepatocellular carcinomaR01EB022148 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI GREEN, JORDAN · 2016 to 2019
$1.5M
NCI NIH HHS R01 CA183827NCI NIH HHS R01 CA195503NCI NIH HHS R01 CA228133NIBIB NIH HHS R01 EB022148
6 · The paper itself

Abstract

Improved delivery materials are needed to enable siRNA transport across biological barriers, including the blood-brain barrier (BBB), to treat diseases like brain cancer. We engineered bioreducible nanoparticles for systemic siRNA delivery to patient-derived glioblastoma cells in an orthotopic mouse tumor model. We first utilized a newly developed biomimetic in vitro model to evaluate and optimize the performance of the engineered bioreducible nanoparticles at crossing the brain microvascular endothelium. We performed transmission electron microscopy imaging which indicated that the engineered nanoparticles are able to cross the BBB endothelium via a vesicular mechanism. The nanoparticle formulation engineered to best cross the BBB model in vitro led to safe delivery across the BBB to the brain in vivo. The nanoparticles were internalized by human brain cancer cells, released siRNA to the cytosol via environmentally-triggered degradation, and gene silencing was obtained both in vitro and in vivo. This study opens new frontiers for the in vitro evaluation and engineering of nanomedicines for delivery to the brain, and reports a systemically administered biodegradable nanocarrier for oligonucleotide delivery to treat glioma.

Indexed as

Blood-Brain BarrierBrain NeoplasmsDrug Delivery SystemsGene SilencingGlioblastomaNanoparticlesRNA, Small InterferingAnimalsHumansMaleMiceMice, NudeXenograft Model Antitumor AssaysRNA, Small Interfering

Identifiers

PMID31612183
PMCPMC6924015

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.