Editors' ChoiceCancer

Bugging cancer with guided swarming

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Science Translational Medicine  07 Sep 2016:
Vol. 8, Issue 355, pp. 355ec142
DOI: 10.1126/scitranslmed.aah6432

Damaging side effects from chemotherapies often delay treatments and can incur fatalities. Even with current drug delivery methods, only a small percentage of the total administered dose reaches its tumor target. The disconnect between increasing drug payloads and reducing patient harm has motivated the development of new drug delivery strategies. Felfoul et al. recently harnessed naturally occurring “magneto-aerotactic” bacteria capable of orienting and migrating along magnetic fields and hypoxic gradients, respectively. The researchers equipped greater than 100 million bacteria with chemotherapy-loaded liposomes, creating an army poised for targeted tumor damage through magnetic guidance. Here, computer-controlled magnetic fields attracted chains of magnetic iron-oxide nanocrystals contained within bacterial magnetosomes. Once propelled to the general zip code of the tumor, aerotactic attraction fine-tuned bacterial transit into low oxygen regions within tumors. As proof-of-concept, peritumoral injections of drug-loaded bacteria into murine xenografts followed by magnetic guidance resulted in greater tumor penetration depths compared with no magnetic guidance.

Selective delivery of treatment to oxygen-depleted regions within tumors offers high potential for therapeutic applications, considering that these regions are often resistant to current therapies. This pilot work, however, needs further expansion to have widespread clinical impact. First, magnetotactic bacteria are notoriously difficult to culture. In particular, they require specific oxygen conditions to form magnetosomes, thus challenging their mass cultivation in standard labs. Second, in the current iteration, magnetic guidance of bacteria within murine xenografts requires specialized, bulky instruments. Customizing such systems for human use could be challenging in terms of required field strengths and system size. Third, guidance of magnetotactic bacteria to deeply situated tumors will likely require molecular imaging modalities. Last, although the current work has reported successful magneto-aerotactic targeting, it has yet to demonstrate therapeutic efficacy using well-controlled animal trials.

Downstream progress should exploit the fruits of artificial intelligence, computer science, drug release chemistry, and microbiology, among other disciplines. Coupled with advanced imaging to visualize and guide future hybrid delivery systems, opportunities for disruptive therapeutic technologies using deployed medical nanorobots offer tremendous promise.

O. Felfoul et al., Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions. Nat. Nanotechnol. 10.1038/nnano.2016.137 (2016). [Abstract]

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