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Spherical nucleic acid (SNA) nanoparticle conjugates to knock down oncogene expression

Systemic delivery of SNAs conjugated to siRNAs could be used to treat glioma. SNAs consist of gold nanoparticles covalently modified with densely packed, oriented siRNA duplexes. In cultured human glioma cell lines and patient- and mouse-derived neurospheres, SNAs conjugated to siRNAs targeting BCL2-like 12 (BCL2L12) decreased expression of BCL2L12 compared with SNAs conjugated to scrambled siRNAs. In mouse models of human glioma, i.v. injection of the SNAs led to their accumulation in tumor but not normal tissue, and SNAs conjugated to siRNAs targeting BCL2L12 decreased expression of BCL2L12 protein and RNA, decreased tumor burden and increased survival compared with control SNAs. Next steps could include elucidating the mechanism of SNA uptake into glioma cells and tumors or using SNA-based systemic delivery of siRNAs to study glioma.

SciBX 6(48); doi:10.1038/scibx.2013.1409
Published online Dec. 19, 2013

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Jensen, S.A. et al. Sci. Transl. Med.; published online Oct. 30, 2013;
doi:10.1126/scitranslmed.3006839
Contact: Alexander H. Stegh, Northwestern University, Chicago, Ill.
e-mail:
a-stegh@northwestern.edu
Contact: Chad A. Mirkin, same affiliation as above
e-mail:
chadnano@northwestern.edu