Nonviral polymeric nanoparticles for gene therapy in pediatric CNS malignancies

Publication date: Available online 23 October 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): 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. JacksonAbstractTogether, 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 provides proof of principle for using biodegradable PBAE nanoparticles as a safe and effective nanomedicine for treating pediatric CNS malignancies.Graphical AbstractPoly(beta-amino ester)s (PBAEs) are biodegradable, cationic polymers that can self-asse...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - Category: Nanotechnology Source Type: research