Editors' ChoiceNanomedicine

Nano Decoy Tricks Venom

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Science Translational Medicine  08 May 2013:
Vol. 5, Issue 184, pp. 184ec78
DOI: 10.1126/scitranslmed.3006451

The cell membrane is a sophisticated border control, regulating the flow of vital compounds into and out of the cell. When this border is compromised, the consequences can be deadly. Most microbes attempt to disrupt this border by using pore-forming toxins (PFTs) to poke holes in the membrane. To “bait” the PFTs before they can damage the cell membrane, Hu et al. designed a material for eliminating different classes of these toxins. Removing the PFTs before they reached the cells extended survival in mice.

Different types of PFTs function similarly in how they integrate into cell membranes; thus, in principle, they can be all targeted at once. Hu and colleagues leveraged this functional similarity and created “nanosponges” by fusing polymer nanoparticles with red blood cell (RBC) membrane vesicles, which absorb PFTs independent of their structural differences. The authors first exposed human endothelial cells to several PFTs, including α-toxin, along with the nanosponges or other therapeutic controls, such as RBC vesicles without the polymeric cores. The nanosponges, in comparison with the controls, were able to neutralize the toxins and thus maintain cell viability. Researchers then subcutaneously injected α-toxin alone or together with the nanosponges into mice. Histology showed that the treatment significantly reduced the inflammatory response and skin and muscle tissue damage. Last, the authors evaluated systemic efficacy of the nanosponges by intraveneously inoculating mice with a lethal dose of α-toxin followed by immediate injection of therapeutic particles. Although none of the mice treated with the controls survived, the nanosponge treatment reduced the mortality rates to 56%.

This work by Hu et al. shows that the RBC membrane vesicles stabilized on polymer nanoparticles are highly effective in neutralizing PFTs, without relying on their immunogenic surface markers. This nanotechnology has the potential to translate into treatments for bacterial infections as well as venomous bites. However, for the system to be ready for the clinic the nanosponges need to prove that they can efficiently clear toxins in much larger blood volumes than mice and when they are administered later than a few minutes after toxin exposure.

C.-M. J. Hu et al., A biomimetic nanosponge that absorbs pore-forming toxins. Nature Nanotechnology, 14 April 2013 (10.1038/nnano.2013.54). [Full Text]

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