Double blow to the tumor

Gold nanostars enhanced the effect of anti-cancer immunotherapy and prevented relapse

Daria Spasskaya, N+1

Researchers from Duke University have combined two well–known cancer therapies – immunotherapy and thermophototherapy - to treat a model metastatic tumor in mice. To improve thermophototherapy, gold nanoparticles in the form of stars, which researchers had previously learned to synthesize, were used as an "energy carrier" heated by a laser. With the help of nanostars, scientists managed to significantly strengthen the antitumor immune response in the body and not only completely cure some mice, but also "vaccinate" them against the development of the same type of tumor. The article Synergistic Immuno Photothermal Nanotherapy (SYMPHONY) for the Treatment of Unresectable and Metastatic Cancers is published in the journal Scientific Reports.

Cancer cells often carry signals on the surface that something is wrong with them - for example, mutated protein molecules recognized by the immune system. However, cancer cells have learned to deceive the immune system. To suppress the immune response against themselves, such cells can express a large amount of the PD-L1 receptor, interaction with which reduces the activity of T-lymphocytes. One of the approaches in cancer immunotherapy is to block the interaction with PD-L1 receptors and thereby restore the natural anti-cancer immune response. This type of therapy is approved for the treatment of solid and metastatic (that is, spreading malignant cells throughout the body) tumors, such as melanoma, lung cancer and bladder cancer.

In order to strengthen the body's natural response to cancer cells, it is better to destroy the tumor – so a larger number of malignant cells will be available for recognition by the immune system. This can be done with the help of thermotherapy – local heating of the tumor site, for example, with a laser. When using nanoparticles, the effectiveness of thermotherapy increases significantly, since the particles increase the conversion of laser energy into heat (they heat up themselves and warm up the surrounding tissues). The authors decided to combine this approach with anti-PD-L1 immunotherapy to enhance the effect of the latter.

In previous work, scientists synthesized gold nanoparticles in the form of stars, which, thanks to a large number of rays, distribute laser energy most efficiently. It has been shown that such particles can be used to visualize tumors, and now the authors have used them for thermotherapy.

In the experiment, tumors were formed in two limbs in mice by injecting cancer cells under the skin. One paw acted as a "primary tumor", and the second as a "metastasis". Nanoparticles were injected into the "primary tumor" and thermotherapy was performed. After that, the mice were injected with a drug used for anti-PD-L1 immunotherapy. In each of the groups (combination of approaches; only thermotherapy; only immunotherapy; only nanoparticles; no treatment) there were five animals.

It turned out that thermotherapy using nanostars significantly improved the effectiveness of immunotherapy. In all mice from this experimental group, both "primary tumors" and "metastases" decreased, which meant activation of their own immune antitumor response. In two mice, all tumors completely disappeared. This effect was not observed in any of the control groups. In the group where only immunotherapy was used, only one mouse had a "secondary tumor" that began to shrink.

Survival schedule of animals with tumors in different groups. In the group with a combination of thermo- and immunotherapy (black squares), 40% of mice survived by the end of the experiment.

One of the cured mice was injected with cancer cells of the same type again a few months after the experiment, but she did not develop a tumor - the animal's own immunity recognized and destroyed the malignant cells. Thus, thermophototherapy with nanoparticles worked as a kind of "vaccination" against this type of cancer (bladder cancer cells were used in the work).

The spread of cancer cells throughout the body (metastasis) and the formation of secondary tumors is a huge problem in the treatment of malignant tumors. The combination of therapeutic approaches, which the authors called SYMPHONY (Synergistic Immuno Photothermal Nanotherapy), has shown promising results for the treatment of metastases, but so far only on a mouse model. At the same time, the use of gold nanoparticles in the thermotherapy of patients is already being tested and may appear in the clinic in the coming years. In the meantime, scientists will have to reproduce the results at least on a larger sample of animals.

Portal "Eternal youth" http://vechnayamolodost.ru  30.08.2017