Biodegradable polymeric nanoparticles show high efficacy and specificity at DNA delivery to human glioblastoma in vitro and in vivo

ACS Nano. 2014 May 27;8(5):5141-53. doi: 10.1021/nn501197v. Epub 2014 Apr 29.


Current glioblastoma therapies are insufficient to prevent tumor recurrence and eventual death. Here, we describe a method to treat malignant glioma by nonviral DNA delivery using biodegradable poly(β-amino ester)s (PBAEs), with a focus on the brain tumor initiating cells (BTICs), the tumor cell population believed to be responsible for the formation of new tumors and resistance to many conventional therapies. We show transfection efficacy of >60% and low biomaterial-mediated cytotoxicity in primary human BTICs in vitro even when the BTICs are grown as 3-D oncospheres. Intriguingly, we find that these polymeric nanoparticles show intrinsic specificity for nonviral transfection of primary human BTICs over primary healthy human neural progenitor cells and that this specificity is not due to differences in cellular growth rate or total cellular uptake of nanoparticles. Moreover, we demonstrate that biodegradable PBAE/DNA nanoparticles can be fabricated, lyophilized, and then stored for at least 2 years without losing efficacy, increasing the translational relevance of this technology. Using lyophilized nanoparticles, we show transgene expression by tumor cells after intratumoral injection into an orthotopic murine model of human glioblastoma. PBAE/DNA nanoparticles were more effective than naked DNA at exogenous gene expression in vivo, and tumor cells were transfected more effectively than noninvaded brain parenchyma in vivo. This work shows the potential of nonviral gene delivery tools to target human brain tumors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Biocompatible Materials / chemistry*
  • Biotechnology
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival
  • DNA / chemistry*
  • Drug Delivery Systems
  • Freeze Drying
  • Gene Expression Regulation
  • Gene Transfer Techniques
  • Genetic Vectors
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Green Fluorescent Proteins / chemistry
  • Humans
  • Mice
  • Nanoparticles / chemistry*
  • Nanotechnology / methods
  • Neoplasm Transplantation
  • Neurons / metabolism
  • Polymers / chemistry
  • Stem Cells / cytology
  • Transfection
  • Transgenes


  • Antineoplastic Agents
  • Biocompatible Materials
  • Polymers
  • Green Fluorescent Proteins
  • DNA