Evidence map›Paper›PMID 28694032›Full record

ArticleJournal of controlled release : official journal of the Controlled Release Society2017

Biodegradable brain-penetrating DNA nanocomplexes and their use to treat malignant brain tumors.

Panagiotis Mastorakos, Clark Zhang, Eric Song, Young Eun Kim, Hee Won Park, Sneha Berry, Won Kyu Choi, Justin Hanes, Jung Soo Suk

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

Article in Journal of controlled release : official journal of the Controlled Release Society, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.5field-weighted citation impact, top 10% 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

28 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
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  10. Mannosylated Polycations Target CD206Biomacromolecules · 2022
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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

9 authors at 2 institutions in 1 country.

Panagiotis MastorakosCenter for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Clark ZhangCenter for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Eric SongCenter for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Biotechnology Education, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, USA.
Young Eun KimDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Hee Won ParkDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Sneha BerryCenter for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Center for Biotechnology Education, Krieger School of Arts and Sciences, Johns Hopkins University, Baltimore, MD, USA.
Won Kyu ChoiDepartment of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA.
Justin HanesCenter for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, USA; Department of Oncology, Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pharmacology & Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: hanes@jhmi.edu.
Jung Soo SukCenter for Nanomedicine, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jsuk@jhmi.edu.
Johns Hopkins Medicine · USJohns Hopkins University · US

Funding

Wilmer Core Grant for Vision ResearchP30EY001765 · NEI · JOHNS HOPKINS UNIVERSITY · PI Ji Yi · 1985 to 2026
$22.1M
Brain Tumor-Penetrating Nanoparticle Delivery with MR-Guided Focused UltrasoundR01CA164789 · NCI · UNIVERSITY OF VIRGINIA · PI HANES, JUSTIN S., PRICE, RICHARD J. · 2012 to 2016
$3.1M
Immunotherapeutic Nanoparticle Delivery to Melanoma With MR-Guided Focused UltrasoundR01CA197111 · NCI · UNIVERSITY OF VIRGINIA · PI BULLOCK, TIMOTHY N, ENGELHARD, VICTOR H · 2015 to 2019
$2.6M
Targeted Delivery of Brain Penetrating DNA Nanoparticles to Brain TumorsR01CA204968 · NCI · JOHNS HOPKINS UNIVERSITY · PI HANES, JUSTIN S., SUK, JUNG SOO · 2016 to 2020
$2.5M
MRI-Guided miRNA Nanoparticle Delivery to Glioblastoma With Focused UltrasoundR01EB020147 · NIBIB · UNIVERSITY OF VIRGINIA · PI HANES, JUSTIN S., PRICE, RICHARD J. · 2015 to 2018
$2.4M
NCI NIH HHS R01 CA164789NCI NIH HHS R01 CA197111NCI NIH HHS R01 CA204968NEI NIH HHS P30 EY001765NIBIB NIH HHS R01 EB020147
6 · The paper itself

Abstract

The discovery of powerful genetic targets has spurred clinical development of gene therapy approaches to treat patients with malignant brain tumors. However, lack of success in the clinic has been attributed to the inability of conventional gene vectors to achieve gene transfer throughout highly disseminated primary brain tumors. Here, we demonstrate ex vivo that small nanocomplexes composed of DNA condensed by a blend of biodegradable polymer, poly(β-amino ester) (PBAE), with PBAE conjugated with 5kDa polyethylene glycol (PEG) molecules (PBAE-PEG) rapidly penetrate healthy brain parenchyma and orthotopic brain tumor tissues in rats. Rapid diffusion of these DNA-loaded nanocomplexes observed in fresh tissues ex vivo demonstrated that they avoided adhesive trapping in the brain owing to their dense PEG coating, which was critical to achieving widespread transgene expression throughout orthotopic rat brain tumors in vivo following administration by convection enhanced delivery. Transgene expression with the PBAE/PBAE-PEG blended nanocomplexes (DNA-loaded brain-penetrating nanocomplexes, or DNA-BPN) was uniform throughout the tumor core compared to nanocomplexes composed of DNA with PBAE only (DNA-loaded conventional nanocomplexes, or DNA-CN), and transgene expression reached beyond the tumor edge, where infiltrative cancer cells are found, only for the DNA-BPN formulation. Finally, DNA-BPN loaded with anti-cancer plasmid DNA provided significantly enhanced survival compared to the same plasmid DNA loaded in DNA-CN in two aggressive orthotopic brain tumor models in rats. These findings underscore the importance of achieving widespread delivery of therapeutic nucleic acids within brain tumors and provide a promising new delivery platform for localized gene therapy in the brain.

Indexed as

Brain NeoplasmsDNANanoparticlesPolyethylene GlycolsPolymersAnimalsBrainFemaleGene ExpressionGenetic TherapyGreen Fluorescent ProteinsRatsRats, Inbred F344Thymidine KinaseTransgenesTumor Suppressor Protein p53DNAGreen Fluorescent Proteinspoly(beta-amino ester)Polyethylene GlycolsPolymersThymidine Kinasethymidine kinase 1Tumor Suppressor Protein p53Viral ProteinsBiodegradable polymerConvection enhanced deliveryDNA nanocomplexNon-viral gene therapyTumor tissue barrier

Identifiers

PMID28694032
PMCPMC5824426
OpenAlexW2729859843

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.