Details

Autor(en) / Beteiligte

• El-Mahdy, Ahmed F. M
• Shibata, Takayuki
• Kabashima, Tsutomu
• Zhu, Qinchang
• Kai, Masaaki

Titel

Delivery of siRNA using siRNA/cationic vector complexes encapsulated in dendrimer-like polymeric DNAs

Ist Teil von

• RSC advances, 2015-01, Vol.5 (41), p.32775-32785

Erscheinungsjahr

2015

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Small interfering RNA (siRNA) is a powerful gene silencing tool and has been considered a potential agent for the treatment of many diseases. However, development of safe and effective siRNA delivery systems still remains a great challenge. In this study, we developed a new siRNA delivery system based on the electrostatic encapsulation of siRNA/cationic vector complexes with dendrimer-like polymeric DNAs (YY-DNAs). The binary complexes of siRNA with cationic vectors such as lipofectamine (LP), polyethylenimine (PEI) and poly- l -lysine (PLL) were first constructed. Then, the encapsulation was performed by the addition of YY-DNAs to the binary complexes in order to form stable complexes of siRNA/LP/YY-DNAs, siRNA/PEI/YY-DNAs and siRNA/PLL/YY-DNAs. The encapsulated siRNA complexes showed nearly spherical morphology with about 13-37 nm average hydrodynamic size and their ζ -potentials were negative. The cationic complexes of siRNA/LP, siRNA/PEI and siRNA/PLL showed a high cytotoxicity towards the cells and strong aggregation with erythrocytes, while their encapsulation into YY-DNAs dramatically decreased the toxicities of complexes. Furthermore, these anionic encapsulated siRNA complexes were highly taken up by the HeLa cells and showed extremely high cellular uptake efficiencies and gene silencing effects without such cytotoxicity and aggregation. The stability of these complexes in 10% FBS and human serum was investigated and they showed high stability even after incubation for 72 h and 48 h, respectively. Therefore, we have newly identified safe and efficient anionic complexes of siRNA for clinical uses. A safe and efficient siRNA delivery system based on the electrostatic encapsulation of binary complexes of siRNA/cationic vector with dendrimer-like polymeric DNAs (YY-DNAs) was developed.