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Nanomedicine applied to acute promyelocytic leukemia treatment via CD44 receptors of macrophages

Grant number: 20/02386-7
Support type:Scholarships in Brazil - Master
Effective date (Start): August 01, 2020
Effective date (End): July 31, 2022
Field of knowledge:Engineering - Materials and Metallurgical Engineering - Nonmetallic Materials
Principal Investigator:Valtencir Zucolotto
Grantee:Luana Corsi Antonio
Home Institution: Instituto de Física de São Carlos (IFSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Macrophages are cells that can adopt distinct polarizations in response to extracellular cues related to several diseases, including cancer. Abundant in solid tumors, tumor-associated macrophages (TAM) are important therapeutic targets. However, not all cancer becomes a solid tumor, for example acute promyelocytic leukemia, although macrophages are also associated with leukemia progression. Nanocarriers (NCs) have been shown to be efficient carriers for macrophage-targeted therapy, e.g. PLGA NCs, which provide a great capacity to carry molecules in their biodegradable and non-toxic core. Several physicochemical properties affect the efficiency of the uptake of NCs by macrophages, including size, shape, charge, and surface binding. Custer determinant 44 (CD44) is a glycoprotein expressed in macrophages that functions as a receptor that binds to hyaluronic acid (HA) and can activate particle uptake, as well as having distinct levels of expression for different macrophage polarizations. Thus, we propose to study the uptake of three PLGA NCs configurations loaded with oxorrubicin - PLGA, PLGA-PEG and PLGA-PEG-AH - in co-cultures of macrophages and leukemic cells. The levels of internalization will be evaluated for all configurations. In addition, the effect of NCs will be studied by cell viability assays, generation of reactive oxygen species and comparison of cell morphology in the absence and presence of NCs, besides observing the internalization of the PLGA-HA NCs by lipopolysaccharide (LPS) activated macrophages. (AU)