Low generation PAMAM dendrimer and CpG free plasmids allow targeted and extended transgene expression in tumors after systemic delivery

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review

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Author(s)

  • Gemma Navarro
  • Gelja Maiwald
  • Rudolf Haase
  • Ernst Wagner
  • Conchita Tros de Ilarduya
  • Manfred Ogris

Detail(s)

Original languageEnglish
Pages (from-to)99-105
Journal / PublicationJournal of Controlled Release
Volume146
Issue number1
Publication statusPublished - Aug 2010

Abstract

Polyplexes consisting of a standard CMV promoter driven luciferase plasmid condensed with PAMAM starburst dendrimers (generation 4 and 5) efficiently transfected tumor cells in vitro. Tail vein injection of PAMAM polyplexes into immune competent mice bearing subcutaneous, well vascularized murine neuroblastoma tumors (Neuro2A) led to predominant luciferase reporter gene expression in the tumor, and negligible transgene expression levels in other organs. Repeated PAMAM polyplex applications were well tolerated and prolonged transgene expression in the tumor. In vivo imaging studies using polyplexes fluorescently labeled with near infrared emitting semiconductor quantum dots (quantoplexes) revealed lung accumulation for both PAMAM and linear PEI (LPEI) based polyplexes, but only LPEI polyplexes induced high luciferase expression in lung, demonstrating that biodistribution and transgene expression of polyplexes does not necessarily correlate. With a luciferase plasmid devoid of immune modulatory CpG sequences and a combination of human CMV enhancer and human elongation factor 1 alpha promoter elements, Neuro2A tumor transgene expression after a single intravenous injection of generation 5 PAMAM polyplexes was observed for up to 1. week as measured by luciferase bioluminescence imaging. Utilizing a human xenograft model (HUH7) in immune compromised nude mice, a low level of luciferase activity in the tumor area was observed after systemic PAMAM polyplex application. © 2010 Elsevier B.V.

Research Area(s)

  • CpG free plasmid, PAMAM dendrimer, Tumor targeting

Citation Format(s)

Low generation PAMAM dendrimer and CpG free plasmids allow targeted and extended transgene expression in tumors after systemic delivery. / Navarro, Gemma; Maiwald, Gelja; Haase, Rudolf et al.
In: Journal of Controlled Release, Vol. 146, No. 1, 08.2010, p. 99-105.

Research output: Journal Publications and ReviewsRGC 21 - Publication in refereed journalpeer-review