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Abstract
For siRNA therapeutics, the use of positively charged amine-rich delivery vectors has been indispensable, but the amine-associated toxicological responses remain a clinical conundrum. Herein, we report a new strategy of harnessing a biocompatible, biodegradable and well-tolerated nanomaterial as an amine-free non-positive carrier for siRNA delivery. By employing mesoporous silica nanoparticles (MSNs) as a biocompatible vector, siRNA is loaded nonconventionally through calcium ion (Ca2+)-mediated interconnection (calcium gluing) between phosphates of siRNA and surface silicates of MSNs in a sequential, cumulative and directional way. The "one-pot" gluing process utilizing endogenously abundant Ca2+ ions offers a simple but robust means of siRNA loading on the non-positive bare surface of MSNs without the aid of multi-amine functionalization, and thus minimizes the risk of amine-associated cytotoxicity and immunogenicity while keeping the intrinsic biocompatibility of MSNs. As demonstrated with loading of an anticancer siRNA, this strategy allows stable in vivo delivery of siRNA for targeted gene silencing, and capitalizes on the unique structural versatility of MSNs by simultaneously delivering a pore-loaded chemodrug to synergistically enhance the treatment efficacy. Therefore, the Ca2+-glued MSNs as a general siRNA carrier platform provide a less toxic, less laborious and more utilitarian delivery tool for more effective and safer siRNA therapeutics.

Author information

Choi E1, Lee J2, Kwon IC1, Lim DK3, Kim S4.
1
Center for Theragnosis, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea.
2
Department of Chemistry, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon, 24341, Republic of Korea.
3
KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea.
4
Center for Theragnosis, Korea Institute of Science and Technology (KIST), Seoul, 136-791, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea; Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology (UST), Seoul, 136-791, Republic of Korea. Electronic address: sehoonkim@kist.re.kr.