Labile catalytic packaging of DNA/siRNA: control of gold nanoparticles "out" of DNA/siRNA complexes

ACS Nano. 2010 Jul 27;4(7):3679-88. doi: 10.1021/nn901796n.

Abstract

A novel approach was developed to efficiently package and deliver nucleic acids with low generation polypropylenimine (PPI) dendrimers by using Au nanoparticles as a "labile catalytic" packaging agent. The gold nanoparticles (Au NPs) helped low generation dendrimers to package nucleic acids into discrete nanoparticles but are not included in the final DNA/siRNA complexes. Therefore it becomes possible to eliminate the potential toxic problems associated with Au NPs by selectively removing the Au NPs from the resulting nucleic acid complexes before their delivery to targeted cells. This is a new concept in using inorganic engineered nanoparticles in nucleic acid packaging and delivery applications. Furthermore, compared to the siRNA nanostructures (mainly randomly aggregated nanofibers) fabricated by low generation dendrimer alone (Generation 3), the siRNA nanoparticles packaged using this novel approach (by Au NPs modified with G3 PPI) can be internalized by cancer cells and the delivered siRNAs can efficiently silence their target mRNA. The efficiency of mRNA silencing by this novel approach is even superior to higher generation dendrimers (Generation 5).

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

  • Base Pairing
  • Base Sequence
  • Biological Transport
  • Catalysis
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA / chemistry*
  • DNA / metabolism
  • Dendrimers / chemistry
  • Drug Carriers / chemistry*
  • Drug Carriers / metabolism
  • Drug Carriers / toxicity
  • Flow Cytometry
  • Gene Knockdown Techniques
  • Gold / chemistry*
  • Gold / metabolism
  • Gold / toxicity
  • Humans
  • Metal Nanoparticles / chemistry*
  • Metal Nanoparticles / toxicity
  • Microscopy, Fluorescence
  • Polypropylenes / chemistry
  • RNA, Small Interfering / chemistry*
  • RNA, Small Interfering / genetics
  • RNA, Small Interfering / metabolism

Substances

  • Dendrimers
  • Drug Carriers
  • Polypropylenes
  • RNA, Small Interfering
  • poly(propyleneimine)
  • Gold
  • DNA