Evidence map›Paper›PMID 37290232›Full record

ArticleBiomaterials2023

Polymeric nanoparticle gel for intracellular mRNA delivery and immunological reprogramming of tumors.

Sarah Y Neshat, Chun Hei Ryan Chan, Jawaun Harris, Osamah M Zmily, Savannah Est-Witte, Johan Karlsson, Sydney R Shannon, Manav Jain, Joshua C Doloff, Jordan J Green and 1 more

Open access · greenAbstract read
In one paragraph

Article in Biomaterials, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
7.1field-weighted citation impact, top 2% 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

22 citing papers in PubMed, 46 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Unlock the sustained therapeutic efficacy of mRNA.Journal of controlled release : official journal of the Controlled Release Society · 2025
    Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Cellular functions and biomedical applications of circular RNAs.Acta biochimica et biophysica Sinica · 2024
    Review
  17. Article
  18. Review
  19. Review
  20. Article
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

11 authors at 2 institutions in 1 country.

Sarah Y NeshatDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Chun Hei Ryan ChanDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Jawaun HarrisDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Osamah M ZmilyDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Savannah Est-WitteDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Johan KarlssonDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Sydney R ShannonDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Manav JainDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
Joshua C DoloffDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, 21218, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA; Department of Oncology, Sidney-Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
Jordan J GreenDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA; Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD, 21218, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA; Department of Oncology, Sidney-Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA; Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA; Departments of Ophthalmology and Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
Stephany Y TzengDepartment of Biomedical Engineering, Translational Tissue Engineering Center, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. Electronic address: stzeng1@jhmi.edu.
Johns Hopkins University · USBloomberg (United States) · US

Funding

TR&D Project 3P41EB028239 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI Jamie Berta Spangler · 2019 to 2026
$11.5M
A PLATFORM TECHNOLOGY TO GENETICALLY REPROGRAM CANCER CELLS FOR ENHANCED IMMUNOTHERAPYR37CA246699 · NCI · JOHNS HOPKINS UNIVERSITY · PI TZENG, STEPHANY YI · 2020 to 2025
$2.6M
A Non-Viral Genetic Vaccine for Prevention and Treatment of Multiple SclerosisR21AI160738 · NIAID · JOHNS HOPKINS UNIVERSITY · PI GREEN, JORDAN · 2021 to 2022
$450k
Tri-Signal Artificial Antigen Presenting Cells for Cancer ImmunotherapyF31CA284859 · NCI · JOHNS HOPKINS UNIVERSITY · PI SHANNON, SYDNEY ROSE · 2023 to 2025
$129k
NCI NIH HHS F31 CA284859NCI NIH HHS R37 CA246699NIAID NIH HHS R21 AI160738NIBIB NIH HHS P41 EB028239
6 · The paper itself

Abstract

Immuno-oncology therapies have been of great interest with the goal of inducing sustained tumor regression, but clinical results have demonstrated the need for improved and widely applicable methods. An antigen-free method of cancer immunotherapy can stimulate the immune system to recruit lymphocytes and produce immunostimulatory factors without prior knowledge of neoantigens, while local delivery reduces the risk of systemic toxicity. To improve the interactions between tumor cells and cytotoxic lymphocytes, a gene delivery nanoparticle platform was engineered to reprogram the tumor microenvironment (TME) in situ to be more immunostimulatory by inducing tumor-associated antigen-presenting cells (tAPCs) to activate cytotoxic lymphocytes against the tumor. Biodegradable, lipophilic poly (beta-amino ester) (PBAE) nanoparticles were synthesized and used to co-deliver mRNA constructs encoding a signal 2 co-stimulatory molecule (4-1BBL) and a signal 3 immuno-stimulatory cytokine (IL-12), along with a nucleic acid-based immunomodulatory adjuvant. Nanoparticles are combined with a thermoresponsive block copolymer for gelation at the injection site for local NP retention at the tumor. The reprogramming nanoparticle gel synergizes with immune checkpoint blockade (ICB) to induce tumor regression and clearance in addition to resistance to tumor rechallenge at a distant site. In vitro and in vivo studies reveal increases in immunostimulatory cytokine production and recruitment of immune cells as a result of the nanoparticles. Intratumoral injection of nanoparticles encapsulating mRNA encoding immunostimulatory agents and adjuvants via an injectable thermoresponsive gel has great translational potential as an immuno-oncology therapy that can be accessible to a wide range of patients.

Indexed as

Antineoplastic AgentsNanoparticlesNeoplasmsAdjuvants, ImmunologicHumansInterleukin-12PolymersRNA, MessengerTumor MicroenvironmentAdjuvants, ImmunologicAntineoplastic AgentsInterleukin-12PolymersRNA, MessengerImmunoengineeringImmuno-oncologyImmunotherapymRNANanoparticlesNonviral gene delivery

Identifiers

PMID37290232
PMCPMC10330908
OpenAlexW4378840474

What Socratic 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 Socratic graph.