Issue 11, 2009

Evaluation of specific delivery of chimeric phi29 pRNA/siRNA nanoparticles to multiple tumor cells

Abstract

The pRNA (packaging RNA) of bacteriophage phi29 DNA packaging motor has been reported to have novel applications in nanotechnology and nanomedicine. The unique ability of pRNA to form dimers, trimers, hexamers and patterned superstructures via the interaction of two reengineered interlocking loops makes it a promising polyvalent vehicle to load siRNA and other therapeutic molecules and be applied as a therapeutic nanoparticle in tumor therapy. In this study, several tumor cell lines were used to evaluate the previously reported pRNA nanotechnology for specific siRNA delivery and for the silencing of targeted gene. It was found that MCF-7 and HeLa cells, out of twenty-five tested tumor cell lines, expressed high levels of folate receptors and exhibited specific binding of the FITC-folate-pRNA nanoparticles, while the others expressed low levels and thus, for these, delivery was not feasible using folate as a targeting agent. Folate receptor positive tumor cells were then incubated with the chimeric pRNA dimer harboring both the folate-pRNA and the chimeric pRNA/siRNA (survivin). Knock down effects of survivin expression in these tumor cells were detected at the mRNA level by real time-PCR and at the protein level by western blot. Apoptosis was detected by flow cytometry analysis with dual staining of annexinV-FITC and PI. The data suggest that the chimeric pRNA nanoparticles containing folate-pRNA and pRNA/siRNA (survivin) could be specifically taken up by tumor cells through folate receptor-mediated endocytosis, resulting in significant inhibition of both transcription and expression of survivin in tumor cells and triggering cell apoptosis. Using such protein-free nanoparticles as therapeutic reagents would not only allow specific delivery and extend the in vivo retaining time but also allow long-term administration of therapeutic particles, therefore avoiding the induction of antibodies caused by repeated treatment for chronic diseases.

Graphical abstract: Evaluation of specific delivery of chimeric phi29 pRNA/siRNA nanoparticles to multiple tumor cells

Additions and corrections

Article information

Article type
Paper
Submitted
26 Feb 2009
Accepted
12 Jun 2009
First published
27 Jul 2009

Mol. BioSyst., 2009,5, 1361-1368

Evaluation of specific delivery of chimeric phi29 pRNA/siRNA nanoparticles to multiple tumor cells

L. Li, J. Liu, Z. Diao, D. Shu, P. Guo and G. Shen, Mol. BioSyst., 2009, 5, 1361 DOI: 10.1039/B903428E

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