Molecularly self-assembled nucleic acid nanoparticles for targeted in vivo siRNA delivery View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-06

AUTHORS

Hyukjin Lee, Abigail K. R. Lytton-Jean, Yi Chen, Kevin T. Love, Angela I. Park, Emmanouil D. Karagiannis, Alfica Sehgal, William Querbes, Christopher S. Zurenko, Muthusamy Jayaraman, Chang G. Peng, Klaus Charisse, Anna Borodovsky, Muthiah Manoharan, Jessica S. Donahoe, Jessica Truelove, Matthias Nahrendorf, Robert Langer, Daniel G. Anderson

ABSTRACT

Nanoparticles are used for delivering therapeutics into cells. 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 efficacy. A variety of materials have been explored for delivering small interfering RNAs (siRNAs)--a therapeutic agent that suppresses the expression of targeted genes. 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 toxicity. 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 (t(1/2) ≈ 24.2 min) than the parent siRNA (t(1/2) ≈ 6 min). More... »

PAGES

389

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/nnano.2012.73

DOI

http://dx.doi.org/10.1038/nnano.2012.73

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1009035919

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22659608


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