Non-adhesive and highly stable biodegradable nanoparticles that provide widespread and safe transgene expression in orthotopic brain tumors.

ABSTRACT: Several generations of poly(β-amino ester) (PBAE) polymers have been developed for efficient cellular transfection. However, PBAE-based gene vectors, similar to other cationic materials, cannot readily provide widespread gene transfer in the brain due to adhesive interactions with the extracellular matrix (ECM). We thus engineered eight vector candidates using previously identified lead PBAE polymer variants but endowed them with non-adhesive surface coatings to facilitate their spread through brain ECM. Specifically, we screened for the ability to provide widespread gene transfer in tumor spheroids and healthy mouse brains. We then confirmed that a lead formulation provided widespread transgene expression in orthotopically established brain tumor models with an excellent in vivo safety pr

SUBMITTER: Negron K 

PROVIDER: S-EPMC8094120 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature