Patch with microneedles against melanoma
Researchers from North Carolina State University and the University of North Carolina at Chapel Hill have developed a technology that allows the use of a biodegradable patch coated with microneedles to deliver antitumor immunopreparations directly to a skin tumor – melanoma.
According to statistics, 67,000 people were diagnosed with melanoma in the United States in 2012 alone. With early detection, the 5-year survival rate for this type of cancer is more than 98%. However, if the tumor has time to metastasize before diagnosis and treatment, this figure drops to 16.6%. Melanoma therapy consists of surgical removal of the tumor focus and chemo- and/or radiotherapy. A new promising area of antitumor therapy is immunotherapy, which mobilizes the body's own immune system to fight the tumor.
The functions of T-lymphocyte immune cells are to identify and destroy tumor cells. To do their job, these cells use specialized receptors that allow them to distinguish healthy cells from cancer cells. However, malignant cells are able to deceive T-lifocytes. One of the misleading techniques of the immune system is the expression of a protein ligand that binds to T-lymphocyte receptors and thus prevents the recognition and destruction of a cancer cell.
Recently, researchers engaged in the development of cancer immunotherapy methods have focused on the use of anti-PD-1 antibodies to prevent the masking of cancer cells from T-lymphocytes.
However, the authors note that the use of such drugs is associated with a number of problems. Firstly, they are usually injected into the bloodstream, which does not allow effective action on the tumor. Secondly, excessive amounts of antibodies can cause side effects, such as the development of autoimmune diseases.
The technology they developed makes it possible to solve both problems simultaneously, since the antibody-coated patch ensures the delivery of anti-PD-1 antibodies directly to the tumor area.
The microneedles covering the patch consist of hyaluronic acid, which is a biocompatible material, into which nanoparticles loaded with antibodies and the enzyme glucose oxidase are integrated.
When applying a patch to a tumor-affected area of the skin, blood penetrates into the microneedles, and the glucose contained in it is converted into gluconic acid under the action of glucose oxidase. The resulting increased acidity of the medium contributes to the gradual destruction of nanoparticles and the release of therapeutic antibodies directly in the tumor area.
A drawing from an article in Nano Letters.
The researchers tested their technique on a mouse model of melanoma. As a comparison therapy, they used intravenous and intra-tumor administration of anti-PD-1. 40 days after the therapy, 40% of the experimental group of mice remained alive, while the surviving animals showed no signs of melanoma. At the same time, the mortality rate of animals of both control groups was 100%.
To further improve the effectiveness of therapy, the authors filled nanoparticles with a cocktail, in addition to anti-PD-1 antibodies containing anti-CTLA-4 antibodies, which also contribute to the effective destruction of tumors by T-lymphocytes. The use of this combination increased the survival rate of animals 40 days after therapy to 70%.
According to the authors, the stable and localized release of drugs provided by microneedles makes it possible to achieve the desired therapeutic effects when using relatively low dosages of drugs, which reduces the risk of developing autoimmune diseases. Currently, they are looking for funding for further research and, ultimately, the introduction of the methodology into clinical practice.
Article by Chao Wang et al. Enhanced Cancer Immunotherapy by Microneedle Patch-Assisted Delivery of Anti-PD1 Antibody is published in the journal Nano Letters.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru Based on materials from North Carolina State University: Microneedle Patch Delivers Localized Cancer Immunotherapy to Melanoma.
25.03.2016