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Nano-delivery could help tackle HIV

Tiny plastic particles could smuggle therapies into cells.

Nanosized spheres could help to stop HIV infection in future. Credit: Nature Materials

Biomedical engineers have found a way of safely delivering potentially therapeutic RNAs into vaginal cells using nanoparticles. The researchers hope similar particles could be used to make topical creams containing anti-HIV RNAs.

Mark Saltzman and his colleagues at Yale University wanted to find a better way to deliver short interfering RNAs (siRNAs) into vaginal cells that might come into contact with HIV. These short snippets of RNA can be designed to repress specific genes, and siRNAs against HIV genes have been shown to stop the virus reproducing in humanized mice. The most common way of getting siRNAs into cells is by attaching it to lipids, but this, Saltzman and colleagues say, is expensive and can be toxic.

Instead, they found a surprisingly simple way to pack thousands of siRNAs into nano-sized bits of a biodegradable and biocompatible plastic that is already approved for medical uses by the US Food and Drug Administration. Such nanoparticles could then be incorporated into a vaginal gel, which could be applied by women before sex to help prevent infection.

"It's surprising that you can load as much siRNA as you can into particles like this," says Saltzman. "It wasn't obvious that it would work."

Spermidine cocktail

The team first mixed the siRNA molecules with spermidine — a natural condensing agent (the name's resemblance to 'sperm' is only a coincidence in this case). This formed the siRNA into clumps, which were then encapsulated in porous plastic particles 100 nanometres across.

Some siRNAs can stop the HIV virus replicating. Credit: Punchstock / Photodisc

Saltzman and his colleagues tested this delivery technique in mice using siRNA that 'silences' or prevents the production of a green fluorescent protein (EGFP). When the loaded nanoparticles were squirted into the vaginas of female mice engineered to produce EGFP, the team could easily see how well their 'medicine' worked by checking if the vaginal cells stopped fluorescing. The nanoparticle-delivery system silenced fluorescence just as well as a traditional lipid delivery system. But, reporting in Nature Materials1 today, the researchers found that the lipid-treated mice developed signs of vaginal irritation, whereas those given the nanoparticles did not.

The nanoparticles also did a good job of spreading siRNA around — deep into vaginal tissue and into the uterus — and released their cargo slowly over a month.

Special delivery

There are a lot of delivery mechanisms for siRNAs, notes John Rossi of the Beckman Research Institute of the City of Hope, Duarte, California, who works on RNAi therapy. Researchers have used everything from cholesterol to empty yeast shells. "None of them is ideal," says Rossi. Some require high doses and so would be too expensive, or aren't targeted enough to the specific organ where the medical problem lurks. The nanoparticle approach is a nice addition, he says: "It's better to have a lot of options."

The Yale team hasn't yet shown their nanoparticles acting against a virus, so it's hard to see how well it stacks up against other microbicides, says Rossi. Besides, he adds, using a topical microbicide of any sort against HIV is a tall order. "It has to be super effective — if just one cell gets by then you've got an infection." Other anti-HIV creams in clinical trials have so far failed to fulfill their early promise (see 'Microbicide gel may help against HIV').

Saltzman is now testing his nanoparticles against the monkey version of HIV, and says it "looks good". But there's a long way to go yet. "The challenge is to show it works against disease," he says.

References

  1. Woodrow K.A. et al. Nature Mater. advanced online publication doi: 10.1038/NMAT2444 (2009).

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Jones, N. Nano-delivery could help tackle HIV. Nature (2009). https://doi.org/10.1038/news.2009.435

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  • DOI: https://doi.org/10.1038/news.2009.435

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