Evidence map›Paper›PMID 31326657›Full record

ArticleBiomaterials2019

Intranasal delivery of targeted polyfunctional gold-iron oxide nanoparticles loaded with therapeutic microRNAs for combined theranostic multimodality imaging and presensitization of glioblastoma to temozolomide.

Uday K Sukumar, Rajendran J C Bose, Meenakshi Malhotra, Husam A Babikir, Rayhaneh Afjei, Elise Robinson, Yitian Zeng, Edwin Chang, Frezghi Habte, Robert Sinclair and 3 more

Abstract 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 107 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 1 pooled it
–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

107 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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  8. PEG-NHInternational journal of nanomedicine · 2026
    Article
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  15. cGAS-agonistic spherical nucleic acids reprogram the glioblastoma immune microenvironment and promote antitumor immunity.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
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47 more citing papers are in PubMed but not listed here.

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

13 authors.

Uday K SukumarCellular Pathway Imaging Laboratory (CPIL), Molecular Imaging Program at Stanford, Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA, 94305, USA.
Rajendran J C BoseCellular Pathway Imaging Laboratory (CPIL), Molecular Imaging Program at Stanford, Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA, 94305, USA.
Meenakshi MalhotraLaboratory of Experimental and Molecular Neuroimaging (LEMNI), Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Drive, Grant Bldg. S031, Stanford, CA, 94305, USA.
Husam A BabikirLaboratory of Experimental and Molecular Neuroimaging (LEMNI), Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Drive, Grant Bldg. S031, Stanford, CA, 94305, USA.
Rayhaneh AfjeiLaboratory of Experimental and Molecular Neuroimaging (LEMNI), Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Drive, Grant Bldg. S031, Stanford, CA, 94305, USA.
Elise RobinsonCellular Pathway Imaging Laboratory (CPIL), Molecular Imaging Program at Stanford, Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA, 94305, USA.
Yitian ZengDepartment of Materials Science and Engineering, Stanford University, Stanford, CA, 94305-4034, United States.
Edwin ChangMultimodality Molecular Imaging Laboratory (MMIL), Molecular Imaging Program at Stanford, Stanford University School of Medicine, Clark Center, 318 Campus Drive, Stanford, CA, 94305, USA.
Frezghi HabteCellular Pathway Imaging Laboratory (CPIL), Molecular Imaging Program at Stanford, Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA, 94305, USA.
Robert SinclairDepartment of Materials Science and Engineering, Stanford University, Stanford, CA, 94305-4034, United States.
Sanjiv S GambhirMultimodality Molecular Imaging Laboratory (MMIL), Molecular Imaging Program at Stanford, Stanford University School of Medicine, Clark Center, 318 Campus Drive, Stanford, CA, 94305, USA.
Tarik F MassoudLaboratory of Experimental and Molecular Neuroimaging (LEMNI), Molecular Imaging Program at Stanford, Stanford University School of Medicine, 300 Pasteur Drive, Grant Bldg. S031, Stanford, CA, 94305, USA. Electronic address: tmassoud@stanford.edu.
Ramasamy PaulmuruganCellular Pathway Imaging Laboratory (CPIL), Molecular Imaging Program at Stanford, Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA, 94305, USA. Electronic address: paulmur8@stanford.edu.

Funding

Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Melinda L. Telli · 2007 to 2026
$71.4M
Nano Characterization and Nano Fabrication CoreU54CA199075 · NCI · STANFORD UNIVERSITY · PI GAMBHIR, SANJIV S · 2015 to 2019
$9.6M
Therapeutic miRNA Modulation of Hepatocellular Carcinoma Using Ultrasound Guided Drug DeliveryR01CA209888 · NCI · STANFORD UNIVERSITY · PI DAHL, JEREMY, PAULMURUGAN, RAMASAMY · 2017 to 2021
$3.1M
Predoctoral Training in Biomedical Imaging at Stanford UniversityT32EB009653 · NIBIB · STANFORD UNIVERSITY · PI BUTTS-PAULY, KIM · 2010 to 2019
$2.1M
3D Passive Cavitation Imaging-Guided Therapeutic Delivery of MicroRNA into CancerR21EB022298 · NIBIB · STANFORD UNIVERSITY · PI PAULMURUGAN, RAMASAMY · 2016 to 2017
$441k
NCI NIH HHS P30 CA124435NCI NIH HHS R01 CA209888NCI NIH HHS U54 CA199075NIBIB NIH HHS R21 EB022298NIBIB NIH HHS T32 EB009653
6 · The paper itself

Abstract

The prognosis for glioblastoma (GBM) remains depressingly low. The biological barriers of the brain present a major challenge to achieving adequate drug concentrations for GBM therapy. To address this, we explore the potential of the nose-to-brain direct transport pathway to bypass the blood-brain barrier, and to enable targeted delivery of theranostic polyfunctional gold-iron oxide nanoparticles (polyGIONs) surface loaded with therapeutic miRNAs (miR-100 and antimiR-21) to GBMs in mice. These nanoformulations would thus allow presensitization of GBM cells to the systemically delivered chemotherapy drug temozolomide (TMZ), as well as in vivo multimodality molecular and anatomic imaging of nanoparticle delivery, trafficking, and treatment effects. First, we synthesized GIONs coated with β-cyclodextrin-chitosan (CD-CS) hybrid polymer, and co-loaded with miR-100 and antimiR-21. Then we decorated their surface with PEG-T7 peptide using CD-adamantane host-guest chemistry. The resultant polyGIONs showed efficient miRNA loading with enhanced serum stability. We characterized them for particle size, PDI, polymer functionalization, charge and release using dynamic light scattering analysis, TEM and qRT-PCR. For in vivo intranasal delivery, we used U87-MG GBM cell-derived orthotopic xenograft models in mice. Intranasal delivery resulted in efficient accumulation of Cy5-miRNAs in mice treated with T7-targeted polyGIONs, as demonstrated by in vivo optical fluorescence and MR imaging. We measured the therapeutic response of these FLUC-EGFP labelled U87-MG GBMs using bioluminescence imaging. Overall, there was a significant increase in survival of mice co-treated with T7-polyGIONs loaded with miR-100/antimiR-21 plus systemic TMZ, compared to the untreated control group, or the animals receiving non-targeted polyGIONs-miR-100/antimiR-21, or TMZ alone. Once translated clinically, this novel theranostic nanoformulation and its associated intranasal delivery strategy will have a strong potential to potentiate the effects of TMZ treatment in GBM patients.

Indexed as

Animalsbeta-CyclodextrinsCell Line, TumorChitosanDrug Delivery SystemsDrug Resistance, NeoplasmFerric CompoundsGlioblastomaGoldHumansMiceMicroRNAsTemozolomideTheranostic NanomedicineXenograft Model Antitumor Assaysbeta-CyclodextrinsbetadexChitosanFerric Compoundsferric oxideGoldMicroRNAsTemozolomideCancer nanotheranosticsGlioblastomaGold iron oxide nanoparticlesLuciferasemiRNA therapeuticsMolecular imagingMR imaging

Identifiers

PMID31326657
PMCPMC6663564

What OpenQuestion holds

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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.