The stiffness of tumors and the collateral damage of standard cancer treatments often block efforts to defeat cancer tumors.

Now, a team of researchers from CNRS, the French National Institute of Health and Medical Research (INSERM), Paris Descartes University, and Paris Diderot University has successfully softened malignant tumors by heating them, using nanomaterial photothermal therapy.

The method, called nanohyperthermia, makes the tumors more vulnerable to therapeutic agents. First, carbon nanotubes (CNTs) are directly injected into the tumors. Then, laser irradiation activates the nanotubes, while the surrounding healthy tissue remains intact.

Double-edged Swords

Researchers are increasingly turning their attention to the mechanical factors impacting the development of cancer tumors. These tumors stiffen due to the abnormal organization of the collagen fibers and extracellular matrix (ECM) that hold cells from the same tissue together.

In addition to being a marker of malignancy, such stiffening may help cancer cells proliferate and metastasize. Furthermore, the ECM forms a physical barrier that limits tumor penetration by therapeutic agents.

Various treatments attempt to disrupt the structure of tumors but are double-edged swords: as extracellular matrix is common to tumors and healthy organs, degrading it does as much harm as good.

The research team found a way around this problem for mouse tumors. After being directly injected into the tumors, CNTs were activated with near-infrared light.

Nanomaterial Photothermal Therapy

The laser only acts on areas of CNT concentration, heating them up. The researchers monitored tumor stiffness noninvasively using ultrasound shear wave elastography. This technique uses the shear or secondary wave produced by ultrasound to map tissue elasticity.

In two consecutive sessions at a day’s interval, the tumors were exposed to nanohyperthermia, or localized heating to 52 °C for a duration of 3 minutes. Tumors initially became more rigid before gradually softening over the 10 days or so that followed the procedure.

Nanohyperthermia denatures collagen fibers locally and reduces the rigidity and volume of tumors over the long term. It disrupts the tumor microenvironment and may prove effective as an adjuvant treatment with chemotherapy.

The research was supported by the Agence Nationale de la Recherche (ANR) P2N program and the LabEx SEAM (Science and Engineering for Advanced Materials and devices), by the Centre National de la Recherche Scientifique (CNRS), and by the International Center for Frontier Research in Chemistry (icFRC).

Iris Marangon et al. Tumor Stiffening, a Key Determinant of Tumor Progression, is Reversed by Nanomaterial-Induced Photothermal Therapy Theranostics (2017). DOI: 10.7150/thno.17574

Image: laser irradiation of nanotube-injected tumor in an anaesthetized mouse. The bar on the right indicates surface temperatures (°C). Credit: Iris Marangon

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