Editors' ChoiceCancer

Nanoreactors get tumor cells hot (but not bothered)

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Science Translational Medicine  08 Apr 2020:
Vol. 12, Issue 538, eabb5666
DOI: 10.1126/scitranslmed.abb5666


A near-infrared light-responsive nanoreactor enables heat ablation of tumors while preventing the inflammatory response to this approach.

Photothermal therapy (PTT) is a promising approach for selective tumor suppression, although inflammation generated during PTT can contribute to tumor recurrence and treatment resistance. Previous studies on PTT used near-infrared lasers to selectively heat nanoparticles in or adjacent to tumor beds. Although tumor growth is initially suppressed by this treatment, localized inflammation can contribute to local recurrence and treatment resistance.

In a series of elegant experiments, Wang et al. demonstrated the synthesis and biological function of an infrared-responsive nanoreactor that can simultaneously heat the surrounding area and catalyze the conversion of local carbon dioxide to carbon monoxide. While the heat destroys cancer cells, the CO acts as a powerful local anti-inflammatory agent suppressing the increase in proinflammatory cytokines that is usually seen in heat-induced necrosis. The researchers used tungsten oxide nanosheets with a critical density of oxygen vacancies to create a material that catalyzes the formation of CO from CO2. They conjugated bicarbonate to the surface to provide a local source of CO2 when heated and added polyethylene glycol to improve the biocompatibility of the material. The resulting nanoreactors were studied in vitro, in cell culture, and in mice. Animals treated with the nanoreactors had their tumors suppressed for the duration of the 60-day experiment without a detectable increase in inflammatory markers. Mice treated with a more traditional PTT material (tungsten sulfide) also had initial suppression of their tumors but had increased inflammatory markers and local tumor recurrence.

Overall, this effort shows a new method of using infrared-activated nanoparticles to simultaneously deliver a treatment and prevent an unwanted side effect. Similar approaches could lead to more targeted, minimally invasive cancer therapies. Although it is important to note that this study uses a single cell line and a single mouse tumor model, it provides a pathway to making PTT a much more useful and widely applied therapy.

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