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.

Targeted Multicomponent Polysomes for High Efficiency, Simultaneous Anti-sense and Gene Delivery.

ROSSO, NATALIA CAROLINA;TIRIBELLI, CLAUDIO;
2011

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11368/2656124
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