Research ArticleNanomedicine

Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma

Science Translational Medicine  30 Oct 2013:
Vol. 5, Issue 209, pp. 209ra152
DOI: 10.1126/scitranslmed.3006839

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Nanotechnology Fights Brain Cancer

Glioblastoma brain tumors are notoriously difficult to kill because the cancer typically recurs after surgical, chemotherapeutic, and biological assault. Now, Jensen and colleagues describe a new nanoparticle conjugate that can cross the blood-brain barrier (BBB), enter the tumor, and target a known oncogene, thus dismantling the cancer-promoting signals and inducing apoptosis of glioma cells.

The nanoparticles, called spherical nucleic acids (SNAs), consisted of densely packed small interfering RNA (siRNA) surrounding a gold core. The siRNA, in this case, targeted the oncogene Bcl2L12 to shut down gene activity in human glioma cell lines and patient-derived tumor neurospheres. When delivered systemically to mice, the SNA nanoparticles rapidly accumulated in the brain—primarily in the tumors—demonstrating their ability to cross the BBB. Animals harboring human brain tumors were then treated with the siRNA-loaded SNAs. Jensen et al. noted impaired tumor growth, likely as the result of increased glioma cell apoptosis, and hence increased survival.

This nanomedicine-based strategy could overcome many of the limitations of traditional cancer therapeutics, including inability to cross the BBB and disseminate throughout brain tissue. To move into patients, however, more optimization of the SNA platform will be necessary, as well as additional testing in animal models of human glioblastoma.