Cyclic RGD-targeting of reversibly stabilized DNA nanoparticles enhances cell uptake and transfection in vitro

Qing Hui Zhou, Ye Zi You, Chao Wu, Yi Huang, David Oupický

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

Reversibly stabilized DNA nanoparticles (rSDN) were prepared by coating reducible polycation/DNA complexes with multivalent N-(2-hydroxypropyl) methacrylamide (HPMA) copolymers. RGD-targeted rSDN were formulated by linking cyclic c(RGDyK) to the surface layer of rSDN. Cellular uptake in B16F10 mouse melanoma cells, human umbilical vein endothelial cells (HUVEC), and THLE immortalized hepatic cells was quantified by real-time PCR. RGD-targeted rSDN exhibited approximately twofold higher cell uptake in integrin-positive cells: B16F10 and HUVEC compared to THLE cells with low integrin content. RGD-targeting mediated increased transfection activity in B16F10 cells but not in THLE cells. Overall, the studies show that rSDN can be effectively targeted with RGD while exhibiting reduced nonspecific cell interactions and favorable stability. As such, these gene delivery vectors have the potential to permit targeting therapeutic genes to tumors by systemic delivery. In addition, the study shows that real-time PCR could be used effectively for the quantification of cellular uptake of gene delivery vectors.

Original languageEnglish (US)
Pages (from-to)364-373
Number of pages10
JournalJournal of Drug Targeting
Volume17
Issue number5
DOIs
StatePublished - Jun 2009
Externally publishedYes

Keywords

  • Gene delivery
  • Gene therapy
  • HPMA
  • RGD
  • Real-time PCR
  • Tumor targeting

ASJC Scopus subject areas

  • Pharmaceutical Science

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