Double nano-impact
One of the main obstacles to creating effective targeted cancer treatments is the diversity of cancer cells. Because of this heterogeneity, it is difficult for the immune system to recognize, respond to a tumor and actively fight cancer cells. However, recent advances in nanotechnology make it possible to deliver targeted personalized "vaccines" for cancer treatment.
A new study demonstrates the use of charged nanoscale organometallic structures to generate free radicals in tumor tissue using X-rays and directly destroy cancer cells. In addition, these same structures can be used to deliver a pathogen-associated molecular pattern (PAMP) that activates an immune response against tumor cells. Combining these two strategies, a new easily administered "vaccine" can become a means for local and systemic therapy of intractable forms of cancer.
A research team from the Faculty of Chemistry and the University of Chicago Medical Center combined the experience of inorganic chemistry and oncology to solve the complex problem of correctly targeting and activating the innate immune response against cancer. In this work, we used the unique properties of nanoscale organometallic lattices (nanoscale metal-organic frameworks, nMOF) – structures constructed from repeating elements capable of penetrating tumors.
If nMOF is exposed to X-rays, the concentration of free radicals in the surrounding tissue will sharply increase, which directly kill cancer cells and, like a vaccine, generate antigens and inflammatory molecules that help the immune system recognize and destroy cancer cells. The lattice structure also makes nMOF ideal carriers of anti-cancer drugs directly into the tumor. The problem for the researchers was the difficulty of activating innate and adaptive immune mechanisms needed to eliminate tumors.
In their new study, the group refined the approach. The new type of nMOF structure allows you to load it with medicines, in particular, PAMP. Now irradiating the tissue had a double effect: it activated nMOF, which killed cancer cells to produce antigens for the immune system, and released PAMP, which then caused a much stronger activation of the immune response to tumor antigens. This two-in-one system was able to kill colon cancer and pancreatic cancer cells with high efficiency, even in tumor models that are highly resistant to other types of immunotherapy.
A model of a nanoscale organometallic framework. Source: Lin Group.
In further experiments on mice, the researchers saw that they could extend the action of nMOF even to distant tumors using checkpoint inhibitors, which gives new hope for cancer treatment using this approach both locally and systemically.
Thus, the nMOF plus PAMP strategy can influence all aspects necessary for the activation of the immune system. The new modification of nMOF can be used for personalized cancer vaccination, and it will be effective because it does not depend on the heterogeneity of cancer cells.
Researchers are already working on improving the technology. They are finalizing the design of nMOF and PAMP delivery for clinical trials. Other versions of nMOF technology are already being tested on humans, and so far the results are encouraging.
Article K.Ni et al. Nanoscale metal-organic frameworks for x-ray activated in situ cancer vaccination is published in the journal Science Advances.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of UChicagoMedicine: New nanotechology design provides hope for personalized vaccination for treating cancer.