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

Karina Negron, Casey Zhu, Shun Wen Chen, Shubin Shahab, Divya Rao, Eric H. Raabe, Charles G. Eberhart, Justin Hanes, Jung Soo Suk

Research output: Contribution to journalArticle

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 profile. Lastly, we developed a method to store it long-term while fully retaining its brain-penetrating property. This new platform provides a broad utility in evaluating novel genetic targets for gene therapy of brain tumors and neurological disorders in preclinical and clinical settings. [Figure not available: see fulltext.].

Original languageEnglish (US)
Pages (from-to)572-581
Number of pages10
JournalDrug Delivery and Translational Research
Volume10
Issue number3
DOIs
StatePublished - Jun 1 2020

Keywords

  • Biodegradable nanoparticles
  • Brain extracellular matrix
  • Brain gene therapy
  • Convection-enhanced delivery
  • Multicellular tumor spheroids

ASJC Scopus subject areas

  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Non-adhesive and highly stable biodegradable nanoparticles that provide widespread and safe transgene expression in orthotopic brain tumors'. Together they form a unique fingerprint.

  • Cite this