HISTAMINE COMBINED STRATEGIES TO IMPROVE THE THERAPEUTIC EFFICACY OF PACLITAXEL IN TRIPLE NEGATIVE BREAST CANCER

NICOUD M.B.; OSPITAL I.; TAQUEZ DELGADO M.; RIEDEL J.; FUENTES P.; BERNABEU E.; MORETTON M.A.; SALGUEIRO J.; CHIAPPETTA D.A.; MEDINA V.A.

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2021; 2021

Breast cancer is the most frequently diagnosed neoplasia and a leading cause of cancer related death in women worldwide. Triple negative breast cancer (TNBC) is an aggressive subtype, associated with poor prognosis. The standard treatment regimen for TNBC is based on the administration of highly toxic chemotherapeutic drugs (anthracyclines/taxanes). Paclitaxel (PTX) is a first-line therapy for TNBC and has low water solubility, poor permeability, and produces severe adverse effects, which limit its clinical use. The aim of this work was to improve the therapeutic index of PTX through the design of combined strategies. For that purpose, we developed nanomicellar polymeric formulations of Soluplus® (S) and Soluplus® surface decorated with glucose residues (SG) co-loaded with histamine (HA, 5 mg/mL) and PTX (4 mg/mL). The micellar size, evaluated by dynamic light scattering, showed a hydrodynamic diameter between 80 and 100 nm for loaded nanoformulations with a unimodal size distribution. Cytotoxicity and apoptosis assays were performed to assess their efficacy in vitro in human MDA-MB-231 and murine 4T1 TNBC cells. Results showed that histamine improved the antitumoral activity of free PTX and Genexol® (commercial micellar-based PTX- nanoformulation) at low concentrations (0.01-0.1 uM) in both cell lines (P