Breathe nanoparticles

At Wake Forest Medical School, which is part of Wake Forest Baptist Health, USA, scientists used mouse models of metastatic lung cancer to determine whether the tumor responds to a system of inhaled immunotherapy with nanoparticles in combination with accepted radiation therapy.

Lung cancer is the second most common malignant tumor and the main cause of cancer death among both men and women. Lung cancer is more likely to die than colon, breast and prostate cancer combined. Despite the rapid development of immunotherapy strategies, they currently work in less than 20% of patients with lung cancer.

An impressive amount of clinical data indicates that at the time of diagnosis in patients, cancer tissue is poorly infiltrated by immune cells. This "cold" immune environment in the tumor does not allow the body's immune system to recognize and destroy tumor cells. Overcoming this immunosuppressive tumor environment to effectively fight cancer is currently an area of scientific interest for researchers.

Previously created methods included direct injection of immunomodulators directly into the tumor to enhance the immune response. However, this approach is limited to use only in cases of superficial and easily accessible tumors and is less effective in cases where repeated injections are necessary to maintain the immune response.

The purpose of this study was to develop a means to transform "cold" tumors into "hot" ones, that is, sensitive to immunity. The researchers wanted it to be non-invasive, allow access to multiple lung tumors at the same time, and be safe for reuse. This new approach would increase the effectiveness of the body's immune system's fight against lung cancer.

The nanoparticle immunotherapy system developed by Douen Zhao and his group delivers immunostimulants to mouse models of metastatic lung cancer by aerosol inhalation. The nanoparticle loaded with an immunostimulator, when deposited in the alveoli of the lung, is absorbed by a specific type of immune cells – antigen-presenting cells.

Then an immunostimulator, cyclic guanosine-adenosine monophosphate, is released from the nanoparticle inside the cell and triggers a certain signaling pathway (interferon gene stimulator, STING), activating antigen-presenting cells. This cascade is an important step for creating a systemic immune response.

The team also showed that inhalation of nanoparticles combined with exposure to radiation therapy on only part of one lung led to regression of tumors in both lungs and prolonged survival of mice. In some mice, tumors in the lungs were completely eliminated.

With the help of mechanistic tests, the group confirmed that the inhalation system transformed the initially "cold" tumors in both lungs into "hot" ones available for powerful anti-cancer immunity.

Zhao's inhaled immunotherapy has several key advantages over previous methods, including the possibility of access to deep lung tumors, because an aerosol with nanoparticles is able to reach all parts of the lung. Another advantage of the new method is the possibility of repeated treatment due to the inhalation dosage form.

It has been shown that the treatment is safe, it is well tolerated by animals, without causing undesirable effects from the immune system.

The authors have filed a preliminary patent application for an inhaled nanoparticle immunotherapy system.

Article Y.Liu et al. An inhalable nanoparticulate STING agonist synergizes with radiotherapy to confer long-term control of lung metastases is published in the journal Nature Communications.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on EurekAlert: Newly developed nanoparticles help fight lung cancer in animal model.