POTENTIAL OF HOMING PEPTIDES TARGETING PRIMARY TUMOR-ASSOCIATED MACROPHAGES FOR NANOTECHNOLOGY SOLID TUMOR TREATMENT

MARIA JOSE GATTAS; ENRIQUE SEBASTIAN CORAPI; AMPARO LAGO HUVELLE; MARIA INES DIAZ BESSONE; DIEGO LADERACH; MARINA SIMIAN

Mar del Plata

Congreso; REUNIÓN ANUAL DE SOCIEDADES DE BIOCIENCIA 2019; 2019

SAIC, SAFE, SAB, SAP, NANOMEDar, AACyTAL

The tumor microenvironment plays a key role in solid tumor growth and progression. A plethora of interactions between the stroma and different types of immune cells are established in a dynamic equilibrium defining patient prognosis. Among these cells we are interested in tumor associated macrophages (TAMs). TAMs originated from blood monocytes display a variety of phenotypes depending on the tumor generated microenvironment. In general, they acquire aM1 antitumoral phenotype during the first stages of cancer progression but as the disease proceeds, they develop a protumoral M2 phenotype, enhancing angiogenesis and contributing to chemotherapy resistance. Our group is focused in developing new strategies for solid tumor treatment using TAM targeted nanoparticles. To do so, we are developing nanoparticles coated with peptides that specifically target M2 macrophages. We established a M2 macrophage mice model to test the effectiveness of multifunctional nanoparticles. We developed M2 macrophages by growing C57BL/C mice bone marrow precursors in different mediums. The control group (CG) grown in DMEM 20 % FCS (D20F), group one (G1) grown in D20F with GMCSF and IL4 and group 2 (G2) grown in D20F and conditioned medium of C6 tumoral cells. Flow citometry of these cells at day 5 reveal that G1 and G2 conditions enhance the expression of CD206, a M2A specific receptor while CG did not. Furthermore, we tested the binding of two different peptides that target TAMs. The CSPGAKVRC peptide (codenamed ?UNO?) that binds specifically to CD206 receptor and the CKRGARSTC peptide (known as ?TT1?) that has affinity for the mitochondrial p32 protein also membrane located in TAMs. Peptides showed specificity in after 30 min incubation at 4º C setting the bases for a potential nanotechnology based strategy for solid tumor treatment.