Development of a polymeric nanostructured system functionalized with a cell membrane and loaded with Imatinib to combat Chronic Myeloid Leukemia

• Grant number: 23/05402-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2023
• End date: May 31, 2024
• Field of knowledge: Engineering - Biomedical Engineering
• Principal Investigator: Valtencir Zucolotto
• Grantee: Flávia Langellotti Silva
• Host Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Leukemia is the most common cancer among children and teenager under the age of 15, in which normal cells are replaced by cancer cells, thus promoting an overproduction of abnormal white blood cells. In this sense, one of the forms of this disease is chronic myeloid leukemia (CML) and, although there are several drugs used in the treatment, such as Imatinib, problems related to that use are noticeable, such as nausea, diarrhea and fatigue, in addition to the development of compound resistance. A possible solution for this problem is the use of nanocarriers, as they can encapsulate drugs, which causes better targeting and reduction of the applied dose. By reducing the drug doses to which the patient is exposed, there is a decrease in the chance of developing resistance to therapy. In addition, these nanostructures can be functionalized with the coating of cell membranes, which increases the targeting of these structures to their targets of action. In the proposed project, polymeric nanoparticles will be synthesized using PLGA, a non-toxic polymer to humans, which will carry the drug Imatinib. These nanoparticles will be functionalized with the cell membrane of the K562 lineage (CML), so that there is both an improvement in the delivery of the drug to its binding site and a disguise of the nanoparticle against the attack of the patient's immune system, which acts against these structures. Furthermore, the tumor microenvironment (TME) will undergo a pre-treatment, before the addition of functionalized nanoparticles, with Esomeprazole, to reduce endocytosis by macrophages and thus increase circulation and therapy performance. As results, it is expected that the nanoparticles are competent in delivering Imatinib with more specificity to cancer cells, resulting in a decrease in the side effects and an increase in treatment success. It is also expected to lower the endocytosis of nanoparticles through the application of Esomeprazole. Thus, it is intended to study a possible new alternative to the treatment of chronic myeloid leukemia, with an improvement in the quality of life during therapy and the prospect of cure.