Nanoliposomes with miRNA against triple negative breast cancer
Researchers at Case Western Reserve University, working under the guidance of Professor William Schiemann, have developed a promising approach to the treatment of triple-negative breast cancer, which consists in combining nanoparticles with small interfering RNAs (miRNAs).
Thrice-negative breast cancer is the most aggressive type of this disease, which currently does not have an approved targeted therapy. In the United States, this type of cancer, mainly affecting women of African descent aged 20 to 40 years, accounts for almost 15% of breast cancer cases. With early detection and timely initiation of treatment, the five-year survival rate of patients with non-metastasized thrice-negative breast cancer is 98%. However, in the presence of distant metastases, this indicator does not even reach 25%.
The process of metastasis of a cancerous tumor is based on the mechanism of epithelial-mesenchymal transition, as a result of which cells change their properties and acquire the ability to break away from the primary tumor and move around the body. One of the necessary conditions for triggering this mechanism is the expression of a gene that regulates the expression of the beta-3-integrin protein.
The researchers suggested that the process of metastasis can be stopped by exposing this gene to miRNA specific to it. Lipid nanoparticles, previously developed by the university staff, called ESO, were chosen as a carrier for therapeutic miRNA. These nanoparticles are able to penetrate the hemato-encephalic barrier, which is the key to successful treatment, since metastatic cells of triple-negative breast cancer often form secondary tumors in brain tissue.
In addition, the ESOs do not degrade in the bloodstream and do not cause reactions from the immune system. They penetrate into malignant cells by induction of the endosomal mechanism, while their composition prevents their adhesion to the endosome membrane and enzymatic cleavage in lysosomes.
Arginylglycylaspartic acid molecules deposited on the surface of nanoparticles (RGD-peptide, tripeptide consisting of L-arginine, glycine and L-aspartic acid, a common element of recognition and protein-protein interaction of cellular proteins) they ensure their selective interaction with the target gene, after attachment to which the nanoparticles release miRNAs that block the production of beta-3-integrin.
The researchers injected the nanoparticle drug into five mice with a mouse analogue of thrice-negative breast cancer every five days for 14 weeks. As a result, the animals had a significant decrease in tumor size and pronounced inhibition of metastases, which was not observed in the control group mice. Similar results were obtained when nanoparticles were injected into mice with implanted tumors of thrice-negative human breast cancer.
Four weeks after the end of treatment, no signs of tumors were detected in the experimental animals, while the tumors of the control group mice continued to grow actively.
The assessment of the condition of animals indicates a slight toxicity of experimental nanoparticles. Currently, researchers are assessing the safety of the therapeutic molecule delivery system they have developed and plan to prepare for its clinical trials in the near future. They note that this technology can be used to target any genes in order to treat not only various types of cancer, but also other diseases.
Article by J. G. Parvani et al. Silencing 3 Integrin by Targeted ECO/siRNA Nanoparticles Inhibits EMT and Metastasis of Triple Negative Breast Cancer is published in the journal Cancer Research.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Case Western Reserve University:
siRNA-toting nanoparticles inhibit breast cancer metastasis.
14.05.2015