Targeted multicomponent polysomes for high efficiency, simultaneous anti-sense and gene delivery

Subhra Mandal, Natalia Rosso, Claudio Tiribelli, Giacinto Scoles, Silke Krol

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Gene therapy is an elegant alternative to chemotherapy, with its well known severe side-effects, as cancer therapy. While viral gene delivery systems bear the risk of infection, polymer-aided delivery suffers low transfection efficacy combined with a relatively high cell toxicity by the used polycations. Here we introduce a targeted polymeric multicomponent submicrometric delivery system delivering simultaneously siRNA and a plasmid to guarantee that both nucleic acids are entering the same cell. The biodegradable 300 nm multilayer particles release siRNA against c-Myc mRNA in order to arrest cell proliferation and then subsequently transfect cancer cells with a wild-type p53 plasmid to induce apoptosis. A high selectivity along with a comparably high transfection efficacy in cancer cells was reached by an electrostatic binding of folic acid to the particle surface. As a result a transfection efficacy and gene expression of around 80-90% was reached in vitro in different cancer cell lines but the particles cause toxicity or apoptosis in only 15% of the healthy cells. The multifunctionality of the electrostatically assembled multilayer nanoparticles significantly improves the transfection efficacy of the non-toxic polycation, chitosan and the combined delivery of siRNA and a plasmid to the same cells holds promises for future gene therapies.

Original languageEnglish
Pages (from-to)9424-9434
Number of pages11
JournalSoft Matter
Volume7
Issue number19
DOIs
Publication statusPublished - Oct 7 2011

Fingerprint

genes
plasmids
delivery
Genes
cancer
Cells
Small Interfering RNA
gene therapy
Gene therapy
Plasmids
apoptosis
cells
toxicity
Toxicity
Multilayers
folic acid
Apoptosis
Chemotherapy
gene expression
Cell proliferation

ASJC Scopus subject areas

  • Chemistry(all)
  • Condensed Matter Physics

Cite this

Targeted multicomponent polysomes for high efficiency, simultaneous anti-sense and gene delivery. / Mandal, Subhra; Rosso, Natalia; Tiribelli, Claudio; Scoles, Giacinto; Krol, Silke.

In: Soft Matter, Vol. 7, No. 19, 07.10.2011, p. 9424-9434.

Research output: Contribution to journalArticle

Mandal, S, Rosso, N, Tiribelli, C, Scoles, G & Krol, S 2011, 'Targeted multicomponent polysomes for high efficiency, simultaneous anti-sense and gene delivery', Soft Matter, vol. 7, no. 19, pp. 9424-9434. https://doi.org/10.1039/c1sm05942d
Mandal, Subhra ; Rosso, Natalia ; Tiribelli, Claudio ; Scoles, Giacinto ; Krol, Silke. / Targeted multicomponent polysomes for high efficiency, simultaneous anti-sense and gene delivery. In: Soft Matter. 2011 ; Vol. 7, No. 19. pp. 9424-9434.
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