Editors' ChoiceNanotechnology

Nanocarriers deliver DNA to brain tumors

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Science Translational Medicine  25 Feb 2015:
Vol. 7, Issue 276, pp. 276ec34
DOI: 10.1126/scitranslmed.aaa8331

Unraveling the molecular mechanisms involved in brain cancer has opened the door to developing new gene therapy approaches. Despite advances in clever therapeutic payloads, there are special challenges that complicate introducing genetic material into cancer cells inside the brain. Mangraviti et al. identify and test polymer formulations capable of transferring DNA into glioma cells. The authors loaded polymeric poly(β-amino ester) particles with genes for herpes simplex virus type 1 thymidine kinase, which converts the prodrug ganciclovir into a cytotoxic compound. The HSVtk nanoparticles were delivered to tumor-bearing rats. The team found that “convection-enhanced delivery”—which relies on positive pressure and constant flow through an infusion pump—through an intracranial catheter allowed the nanoparticles to spread throughout the brain tumors, inducing glioma cells to express the HSVtk enzyme. When ganciclovir was administered to the animals systemically, it resulted in a significant survival benefit for treated rats compared with controls treated with nanoparticles encoding green fluorescent protein—presumably because the toxic ganciclovir derivative was produced in the transfected cancer cells.

This new approach to treating brain tumors is preliminary. Although inexpensive and safe, the nanoparticles were not directly compared with viral vectors, which are costly and may elicit undesired immune responses, but are already undergoing clinical testing. If the polymeric nanoparticles translate to the clinic, brain cancer patients could be treated without eliciting strong neutralizing antibody responses, which is currently one of the biggest setbacks for oncolytic virus therapy. In the future, these nanoparticles may also be targeted to molecules expressed on brain tumors and administered intravenously rather than directly to the brain, which would spare patients from repetitive operations and extended hospital stays.

A. Mangraviti et al., Polymeric nanoparticles for nonviral gene therapy extend brain tumor survival in vivo. ACS Nano 10.1021/nn504905q (2015). [Full Text]

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