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

Hugo Guerrero Cazares, Stephany Y. Tzeng, Noah P. Young, Ameer O. Abutaleb, Alfredo Quinones-Hinojosa, Jordan J. Green

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5141-5153
Number of pages13
JournalACS Nano
Volume8
Issue number5
DOIs
StatePublished - May 27 2014
Externally publishedYes

Fingerprint

Glioblastoma
Brain Neoplasms
Nanoparticles
Neoplastic Stem Cells
Tumors
delivery
DNA
tumors
deoxyribonucleic acid
nanoparticles
brain
Brain
Neoplasms
Transfection
Cells
Biocompatible Materials
Transgenes
Glioma
therapy
Esters

Keywords

  • glioblastoma
  • nanomedicine
  • nonviral gene delivery
  • targeted delivery

ASJC Scopus subject areas

  • Engineering(all)
  • Materials Science(all)
  • Physics and Astronomy(all)
  • Medicine(all)

Cite this

Biodegradable polymeric nanoparticles show high efficacy and specificity at DNA delivery to human glioblastoma in vitro and in vivo. / Guerrero Cazares, Hugo; Tzeng, Stephany Y.; Young, Noah P.; Abutaleb, Ameer O.; Quinones-Hinojosa, Alfredo; Green, Jordan J.

In: ACS Nano, Vol. 8, No. 5, 27.05.2014, p. 5141-5153.

Research output: Contribution to journalArticle

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