Evidence map›Paper›PMID 31026613›Full record

ArticleBiomaterials2019

Cancer-selective nanoparticles for combinatorial siRNA delivery to primary human GBM in vitro and in vivo.

Kristen L Kozielski, Alejandro Ruiz-Valls, Stephany Y Tzeng, Hugo Guerrero-Cázares, Yuan Rui, Yuxin Li, Hannah J Vaughan, Marissa Gionet-Gonzales, Casey Vantucci, Jayoung Kim and 4 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
4.5field-weighted citation impact, top 4% 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

57 citing papers in PubMed, 106 citations in OpenAlex.

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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 at 3 institutions in 2 countries.

Kristen L KozielskiDepartment of Biomedical Engineering, Translational Tissue Engineering Center, And Institute for NanoBioTechnology, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA; Max Planck Institute for Intelligent Systems, Heisenbergstr. 3, Stuttgart, 70569, Germany.
Alejandro Ruiz-VallsDepartments of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
Stephany Y TzengDepartment of Biomedical Engineering, Translational Tissue Engineering Center, And Institute for NanoBioTechnology, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA.
Hugo Guerrero-CázaresDepartments of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA; Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, 32224, USA.
Yuan RuiDepartment of Biomedical Engineering, Translational Tissue Engineering Center, And Institute for NanoBioTechnology, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA.
Yuxin LiDepartments of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
Hannah J VaughanDepartment of Biomedical Engineering, Translational Tissue Engineering Center, And Institute for NanoBioTechnology, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA.
Marissa Gionet-GonzalesDepartment of Biomedical Engineering, Translational Tissue Engineering Center, And Institute for NanoBioTechnology, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA.
Casey VantucciDepartment of Biomedical Engineering, Translational Tissue Engineering Center, And Institute for NanoBioTechnology, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA.
Jayoung KimDepartment of Biomedical Engineering, Translational Tissue Engineering Center, And Institute for NanoBioTechnology, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA.
Paula SchiapparelliDepartments of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA; Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, 32224, USA.
Rawan Al-KharbooshDepartments of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA; Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, 32224, USA.
Alfredo Quiñones-HinojosaDepartments of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA; Department of Neurosurgery, Mayo Clinic, Jacksonville, FL, 32224, USA. Electronic address: Quinones@mayo.edu.
Jordan J GreenDepartment of Biomedical Engineering, Translational Tissue Engineering Center, And Institute for NanoBioTechnology, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA; Departments of Neurosurgery and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA; Department of Materials Science and Engineering, Department of Chemical and Biomolecular Engineering, Department of Ophthalmology, The Sidney Kimmel Comprehensive Cancer, And the Bloomberg∼Kimmel Institute for Cancer Immunotherapy, Johns Hopkins School of Medicine, Baltimore, MD, 21231, USA. Electronic address: Green@jhu.edu.
Johns Hopkins University · USJohns Hopkins Medicine · USBloomberg (United States) · US

Funding

T32: Predoctoral and Postdoctoral Training Program in Nanotechnology for Cancer ResearchT32CA153952 · NCI · JOHNS HOPKINS UNIVERSITY · PI Denis Wirtz · 2015 to 2026
$3.5M
Gene Delivery Nanoparticles to Treat GlioblastomaR01EB016721 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI GREEN, JORDAN · 2013 to 2017
$1.9M
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
Gene Delivery Nanoparticles to Treat GlioblastomaR01CA228133 · NCI · JOHNS HOPKINS UNIVERSITY · PI GREEN, JORDAN · 2019 to 2023
$1.9M
T-32 NIH Postdoctoral Training Program in Nanotechnology for Cancer Medicine NTCMT32CA130840 · NCI · JOHNS HOPKINS UNIVERSITY · PI WIRTZ, DENIS · 2008 to 2012
$1.2M
Role of Human Cerebrospinal Fluid Chemokines in the Invasiveness of Human GlioblastomaR21CA199295 · NCI · MAYO CLINIC JACKSONVILLE · PI GUERRERO-CAZARES, HUGO · 2016 to 2017
$384k
Nanoparticles for selective and combinatorial delivery of siRNA to brain cancerF31CA196163 · NCI · JOHNS HOPKINS UNIVERSITY · PI KOZIELSKI, KRISTEN LYNN · 2015 to 2016
$68k
NCI NIH HHS F31 CA196163NCI NIH HHS R01 CA195503NCI NIH HHS R01 CA228133NCI NIH HHS R21 CA199295NCI NIH HHS T32 CA130840NCI NIH HHS T32 CA153952NIBIB NIH HHS R01 EB016721
6 · The paper itself

Abstract

Novel treatments for glioblastoma (GBM) are urgently needed, particularly those which can simultaneously target GBM cells' ability to grow and migrate. Herein, we describe a synthetic, bioreducible, biodegradable polymer that can package and deliver hundreds of siRNA molecules into a single nanoparticle, facilitating combination therapy against multiple GBM-promoting targets. We demonstrate that siRNA delivery with these polymeric nanoparticles is cancer-selective, thereby avoiding potential side effects in healthy cells. We show that we can deliver siRNAs targeting several anti-GBM genes (Robo1, YAP1, NKCC1, EGFR, and survivin) simultaneously and within the same nanoparticles. Robo1 (roundabout homolog 1) siRNA delivery by biodegradable particles was found to trigger GBM cell death, as did non-viral delivery of NKCC1, EGFR, and survivin siRNA. Most importantly, combining several anti-GBM siRNAs into a nanoparticle formulation leads to high GBM cell death, reduces GBM migration in vitro, and reduces tumor burden over time following intratumoral administration. We show that certain genes, like survivin and EGFR, are important for GBM survival, while NKCC1, is more crucial for cancer cell migration. This represents a powerful platform technology with the potential to serve as a multimodal therapeutic for cancer.

Indexed as

Gene Transfer TechniquesAnimalsBrain NeoplasmsCell Line, TumorGene Knockdown TechniquesGlioblastomaHumansMice, NudeNanoparticlesPolymersRNA, Small Interferingpoly(beta-amino ester)PolymersRNA, Small InterferingCancer therapyCombination therapyGene therapyNanoparticlesiRNA

Identifiers

PMID31026613
PMCPMC7122460
OpenAlexW2935899679

What OpenQuestion holds

Textmetadata
LicenceTDM
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.