Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery
- 주제(키워드) Nanobiotechnology , Nanomedicine
- 후원정보 This work was supported by the National Institutes of Health (EB000244), the Center for Cancer Nanotechnology Excellence (U54 CA151884), Alnylam Pharmaceuticals and the National Research Foundation of Korea (NRF-2011-357-D00063).
- 설명문(URI) http://www.nature.com/nnano/journal/v7/n6/covers/index.html
- 등재 SCIE, SCOPUS
- 발행기관 Nature Publishing Group
- 발행년도 2012
- 원문페이지 5 p.
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000072989
- 본문언어 영어
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
Nanoparticles are used for delivering therapeutics into cells1, 2. However, size, shape, surface chemistry and the presentation of targeting ligands on the surface of nanoparticles can affect circulation half-life and biodistribution, cell-specific internalization, excretion, toxicity and efficacy3, 4, 5, 6, 7. A variety of materials have been explored for delivering small interfering RNAs (siRNAs)—a therapeutic agent that suppresses the expression of targeted genes8, 9. However, conventional delivery nanoparticles such as liposomes and polymeric systems are heterogeneous in size, composition and surface chemistry, and this can lead to suboptimal performance, a lack of tissue specificity and potential toxicity10, 11, 12. Here, we show that self-assembled DNA tetrahedral nanoparticles with a well-defined size can deliver siRNAs into cells and silence target genes in tumours. Monodisperse nanoparticles are prepared through the self-assembly of complementary DNA strands. Because the DNA strands are easily programmable, the size of the nanoparticles and the spatial orientation and density of cancer-targeting ligands (such as peptides and folate) on the nanoparticle surface can be controlled precisely. We show that at least three folate molecules per nanoparticle are required for optimal delivery of the siRNAs into cells and, gene silencing occurs only when the ligands are in the appropriate spatial orientation. In vivo, these nanoparticles showed a longer blood circulation time (t1/2 ≈ 24.2 min) than the parent siRNA (t1/2 ≈ 6 min).
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