Non-viral gene delivery nanoparticles based on poly(β-amino esters) for treatment of glioblastoma

Biomaterials. 2011 Aug;32(23):5402-10. doi: 10.1016/j.biomaterials.2011.04.016. Epub 2011 May 4.

Abstract

Glioblastoma (GB) is currently characterized by low survival rates and therapies with insufficient efficacy. Here, we describe biodegradable polymers that can deliver genes to primary GB cells as well as GB tumor stem cells in vitro with low non-specific toxicity and transfection efficiencies of up to 60.6 ± 5% in normal (10%) serum conditions. We developed polymer-DNA nanoparticles that remained more stable in normal serum and could also be stored for at least 3 months in ready-to-use form with no measurable decrease in efficacy, expanding their potential in a practical or clinical setting. A subset of polymers was identified that shows a high degree of specificity to tumor cells compared with healthy astrocytes and human neural stem cells when cultured (separately or in co-culture), yielding higher transfection in GB cells while having little to no apparent effect on healthy cells.

Publication types

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

MeSH terms

  • Astrocytes / cytology
  • Astrocytes / metabolism
  • Carbocyanines / chemistry
  • Cell Line, Tumor
  • Cell Survival
  • Cryoprotective Agents / chemistry
  • DNA / chemistry
  • DNA / metabolism
  • Fetal Stem Cells / cytology
  • Fetal Stem Cells / metabolism
  • Freeze Drying / methods
  • Gene Expression / genetics
  • Gene Transfer Techniques*
  • Glioblastoma / therapy*
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / metabolism
  • Humans
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Nanoparticles / chemistry*
  • Neoplastic Stem Cells / cytology
  • Neoplastic Stem Cells / metabolism
  • Polymers / chemical synthesis
  • Polymers / chemistry*
  • Red Fluorescent Protein
  • Spheroids, Cellular / cytology
  • Spheroids, Cellular / metabolism
  • Sucrose / chemistry
  • Time Factors
  • Transfection

Substances

  • Carbocyanines
  • Cryoprotective Agents
  • Luminescent Proteins
  • Polymers
  • cyanine dye 3
  • enhanced green fluorescent protein
  • poly(beta-amino ester)
  • Green Fluorescent Proteins
  • Sucrose
  • DNA