Crack the shell of cancer
A research group from Southwest Texas University has created a method of microbubble-assisted Ultrasound-guided Immunotherapy of cancer with ultrasound guidance (Microbubble-assisted Ultrasound-guided Immunotherapy of Cancer, MUSIC), which consists in the introduction of microbubbles followed by ultrasound exposure. It can be used to obtain a clearer ultrasound image of the heart, to overcome the blood-brain barrier in the delivery of drugs against Alzheimer's disease or the destruction of arterial plaque. The technology can also be used to treat cancer: if micro-bubbles are injected into a malignant cell and then blown up with ultrasound, mechanical stress will destroy the cell.
The creators of MUSIC suggested using the system for drug delivery, and not for the direct destruction of cancer cells. Under the influence of an ultrasonic field, microbubbles oscillate, and if these bubbles bind to cells, then when exposed to a sufficiently high intensity of ultrasound, the vibrations will push and pull the cell membrane. This creates pores through which the contents of the microbubbles enter the cell.
The researchers placed a cyclic dinucleotide c GAMP inside the microbubbles, which enhances the immune response to tumors by activating the c GAS-STING signaling pathway. Previously, cGAMP delivery was limited due to instability and low penetration rate into the cell.
Microbubbles also carry antibodies that help them specifically target antigen-presenting cells, penetrate them, thanks to ultrasound-induced vibrations of the cell membrane, and trigger cGAS-STING. This, in turn, activates immune T cells to attack tumor cells.
In experiments on mouse models of triple negative breast cancer, it was found that the described method significantly reduces tumor growth, 60% of treated mice showed complete eradication of the tumor. In addition, the method generated antitumor immune memory in T cells, which prevented tumor recurrence.
In separate experiments on mouse models of metastatic cancer, the group found that MUSIC activates a powerful T-cell response that forces cells to travel long distances to fight metastases in different parts of the body. The addition of the immunotherapy drug pemrolizumab , a PD–1 inhibitor, to the mixture prevented further progression of the disease. This combination therapy resulted in a 76% higher average survival rate than isolated treatment with a PD-1 inhibitor.
The fact that microbubbles are already widely used as a contrast agent in ultrasound diagnostics speaks in favor of the imminent clinical use of the technology. MUSIC appears to have low toxicity, and the authors believe that such a delivery method will help avoid inflammatory complications often observed with other methods of administration of c GAMP.
Article X.Li et al. Cancer immunotherapy based on image-guided STING activation by nucleotide nanocomplex-decorated ultrasound microbubbles is published in the journal Nature Nanotechnology.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru