Editors' ChoiceNanomedicine

Friendly Bacteria

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Science Translational Medicine  22 Jan 2014:
Vol. 6, Issue 220, pp. 220ec15
DOI: 10.1126/scitranslmed.3008435

Bacteria—the body’s usual foe—has become a friend. By commandeering bacteria’s internal machinery, Gujrati et al. created genetically engineered bacteria that produced nanometer-sized vesicles. These vesicles attacked cancer cells and prevented tumor growth in mice.

Although nanoparticle drug delivery vehicles are promising for cancer therapy, their potential accumulation in the body remains a challenge for translation. Therefore, Gujrati and colleagues turned to Gram-negative bacteria, which shed degradable outer membrane vesicles (OMVs) 30 to 250 nm in diameter, as novel drug delivery vehicles. The OMVs display proteins against specific cellular targets and are customizable by genetically tweaking the bacteria. In addition, the vesicles can carry therapeutics for delivery to the target cells in vivo. To prevent an immune response once given to animals, the authors chose the Escherichia coli strain K-12 W3110 that produces a less-potent form of lipopolysaccharide (a pro-inflammatory molecule) and disabled blood-damaging toxins by fusing them with affibodies. In this case, these highly specific small, antibody-like proteins, called affibodies, targeted human epidermal growth factor receptor (HER2), which is overexpressed in cancer cells. For the therapeutic function, the authors loaded the engineered OMVs with small interfering RNA (siRNA) against kinesin spindle protein, which plays an important role in cell division and cancer cell proliferation. The scientists injected several doses of siRNA-loaded OMVs every other day to mice with human tumors that overexpressed HER2. Compared with controls—including free siRNA, nontargeting OMVs, and saline-loaded OMVs—the test particles selectively and significantly reduced tumor growth with minimal side effects.

Overall, bacterial OMVs have high translational potential because of their customizable targeting membrane proteins and therapeutic cargo, as well as compatibility with mass production in bacterial growth tanks. However, before clinical use, more studies are necessary to ensure that OMVs are nontoxic in larger animals and can indeed be scaled up to the quantities needed for treating patients.

V. Gujrati et al., Bioengineered bacterial outer membrane vesicles as cell-specific drug-delivery vehicles for cancer therapy. ACS Nano published online 10 January 2014 (10.1021/nn405724x). [PubMed]

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