Editors' ChoiceCancer

A new approach to local drug delivery bubbling under the surface

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Science Translational Medicine  31 Jul 2019:
Vol. 11, Issue 503, eaay3582
DOI: 10.1126/scitranslmed.aay3582

Abstract

Ultrasound is coupled with a needle-based minimally invasive electrode to enhance targeted drug delivery to superficial tumors.

Conventional chemotherapeutics are delivered systemically and are often not that well targeted to specific tumor sites. Therefore, it is unsurprising that when only a fraction of the chemotherapeutics administered end up at the tumor site; the remainder can lead to significant side effects. Getting more drug to act at the target tumor could lead to dose-sparing and associated health benefits.

One of the strategies proposed to increase drug uptake in superficial tumors is to create microbubbles that temporarily disrupt the membranes of cells locally using an ultrasound probe, a process known as sonoporation. Zandi and colleagues identified a potential deficiency with this approach: The microcavitations induced by ultrasound alone may be insufficient to cause significant changes in local drug uptake. To overcome this issue, they coupled ultrasound-assisted drug delivery with a custom microfabricated needle electrode. When the electrode is inserted transcutaneously into the tumor and electrolyzes the local interstitial fluid, more microbubbles appear that can be popped by the ultrasound wave. To test the efficacy of their system, they tested various combinations of these approaches in a breast tumor model in mice. When the electrolysis and ultrasound were combined with a low dose of intravenously administered chemotherapeutic, the tumors shrank drastically (by 82%) within 10 days and had disappeared entirely after 16 days. This shrinkage was in marked contrast to other study groups with only some of these interventions, where modest shrinkage or growth occurred.

Many questions remain before this type of approach could translate to clinical use. Although the tumor shrinkage results are encouraging, it would be valuable to see direct visual evidence of enhanced drug permeation in vivo, perhaps through the addition of fluorescent agents. As this treatment scales to larger models that are more representative of human anatomy its efficacy may be challenged. The additional microbubbles required could increase the risk of air embolism and other potential complications. Despite using a very sharp low profile, the relative invasiveness and clinical acceptance of the needle electrode are not yet determined. For now, though, it is satisfying to see microbubbles in cancer cells go pop.

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