Single stranded siRNA complexation through non-electrostatic interactions.
As double stranded, single stranded siRNA (ss-siRNA) has demonstrated gene silencing activity but still requires efficient carriers to reach its cytoplasmic target. To better understand the fundamental aspect driving the complexation of ss-siRNA with nanocarriers, the interactions between surfaces of various compositions across a ss-siRNA solution were investigated using the Surface Forces Apparatus. The results show that ss-siRNA can adsorb onto hydrophilic (positively and negatively charged) as well as on hydrophobic substrates suggesting that the complexation can occur through hydrophobic interactions and hydrogen bonding in addition to electrostatic interactions. Moreover, the binding strength and the conformation of ss-siRNA depend on the nature of the interactions between the ss-siRNA and the surfaces. The binding of ss-siRNA with nanocarriers, such as micelles or liposomes through non-electrostatic interactions was also evidenced by a SYBR®Gold cyanine dye. We evidenced the presence of interactions between the dye and oligonucleotides already complexed to non-cationic nanovectors biasing the quantification of the encapsulation. These results suggest that non-electrostatic interactions could be exploited to complement electrostatic interactions in the design of nanocarriers. In particular, the different highlighted interactions can be used to complex ss-siRNA with uncharged or anionic carriers which are related to lower toxicity compared to cationic carriers.
Faculty of Pharmacy, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada.
Lucie
L
Giraud
Faculty of Pharmacy, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada.
Warren
W
Viricel
Faculty of Pharmacy, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada.
Jeanne
J
Leblond
Faculty of Pharmacy, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada; Department of Chemistry, Université de Montréal, C.P. 6128, Succursale Centre-ville, Montréal, Québec H3C 3J7, Canada. Electronic address: suzanne.giasson@umontreal.ca.
Suzanne
S
Giasson
D000327:Adsorption; D001665:Binding Sites; D002412:Cations / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes / Q000737:chemistry*; D008823:Micelles; D009690:Nucleic Acid Conformation; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry; D055672:Static Electricity
D002412:Cations; D008081:Liposomes; D008823:Micelles; D034741:RNA, Small Interfering
Hydrogen bonding; Hydrophobic interactions; Single stranded RNA; Surfaces Forces Apparatus