Nonviral polymeric nanoparticles for gene therapy in pediatric CNS malignancies

John Choi, Yuan Rui, Jayoung Kim, Noah Gorelick, David R. Wilson, Kristen Kozielski, Antonella Mangraviti, Eric Sankey, Henry Brem, Betty Tyler, Jordan J. Green, Eric M. Jackson

Research output: Contribution to journalArticle

Abstract

Together, medulloblastoma (MB) and atypical teratoid/rhabdoid tumors (AT/RT) represent two of the most prevalent pediatric brain malignancies. Current treatment involves radiation, which has high risks of developmental sequelae for patients under the age of three. New safer and more effective treatment modalities are needed. Cancer gene therapy is a promising alternative, but there are challenges with using viruses in pediatric patients. We developed a library of poly(beta-amino ester) (PBAE) nanoparticles and evaluated their efficacy for plasmid delivery of a suicide gene therapy to pediatric brain cancer models—specifically herpes simplex virus type I thymidine kinase (HSVtk), which results in controlled apoptosis of transfected cells. In vivo, PBAE-HSVtk treated groups had a greater median overall survival in mice implanted with AT/RT (P = 0.0083 vs. control) and MB (P < 0.0001 vs. control). Our data provide proof of principle for using biodegradable PBAE nanoparticles as a safe and effective nanomedicine for treating pediatric CNS malignancies.

Original languageEnglish (US)
Article number102115
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume23
DOIs
StatePublished - Jan 2020

Fingerprint

Gene therapy
Pediatrics
Genetic Therapy
Nanoparticles
Viruses
Esters
Medulloblastoma
Thymidine Kinase
Simplexvirus
Tumors
Brain
Neoplasms
Nanomedicine
Medical nanotechnology
Neoplasm Genes
Cell death
Brain Neoplasms
Suicide
Libraries
Plasmids

Keywords

  • Atypical teratoid/rhabdoid tumor
  • Cancer
  • Medulloblastoma
  • Pediatrics
  • Poly(beta-amino ester) nanoparticle

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

Cite this

Nonviral polymeric nanoparticles for gene therapy in pediatric CNS malignancies. / Choi, John; Rui, Yuan; Kim, Jayoung; Gorelick, Noah; Wilson, David R.; Kozielski, Kristen; Mangraviti, Antonella; Sankey, Eric; Brem, Henry; Tyler, Betty; Green, Jordan J.; Jackson, Eric M.

In: Nanomedicine: Nanotechnology, Biology, and Medicine, Vol. 23, 102115, 01.2020.

Research output: Contribution to journalArticle

Choi, John ; Rui, Yuan ; Kim, Jayoung ; Gorelick, Noah ; Wilson, David R. ; Kozielski, Kristen ; Mangraviti, Antonella ; Sankey, Eric ; Brem, Henry ; Tyler, Betty ; Green, Jordan J. ; Jackson, Eric M. / Nonviral polymeric nanoparticles for gene therapy in pediatric CNS malignancies. In: Nanomedicine: Nanotechnology, Biology, and Medicine. 2020 ; Vol. 23.
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