A Tri-Stimuli Responsive (Maghemite/PLGA)/Chitosan Nanostructure with Promising Applications in Lung Cancer

This research was funded by Instituto de Salud Carlos III (ISCIII) (project PI19/01478) (FEDER), Programa Operativo FEDER de Andalucia 2014-2020 (Junta de Andalucia, project I + D + i A1-FQM-341-UGR18), and Programa de Ayudas a Proyectos I + D + i destinadas a Universidades y Entidades Publicas de Investigacion (Junta de Andalucia, project PY20_00346).A (core/shell)/shell nanostructure (production performance 50%,mean diameter 330 nm) was built using maghemite, PLGA, and chitosan. An extensive characterization proved the complete inclusion of the maghemite nuclei into the PLGA matrix (by nanoprecipitation solvent evaporation) and the disposition of the chitosan shell onto the nanocomposite (by coacervation). Short-term stability and the adequate magnetism of the nanocomposites were demonstrated by size and electrokinetic determinations, and by defining the first magnetization curve and the responsiveness of the colloid to a permanent magnet, respectively. Safety of the nanoparticles was postulated when considering the results from blood compatibility studies, and toxicity assays against human colonic CCD-18 fibroblasts and colon carcinoma T-84 cells. Cisplatin incorporation to the PLGA matrix generated appropriate loading values ( 15%), and a dual pH- and heat (hyperthermia)-responsive drug release behaviour ( 4.7-fold faster release at pH 5.0 and 45 C compared to pH 7.4 and 37 C). The half maximal inhibitory concentration of the cisplatin-loaded nanoparticles against human lung adenocarcinoma A-549 cells was 1.6-fold less than that of the free chemotherapeutic. Such a biocompatible and tri-stimuli responsive (maghemite/PLGA)/chitosan nanostructure may found a promising use for the effective treatment of lung cancer.Instituto de Salud Carlos III European Commission PI19/01478Programa Operativo FEDER de Andalucia 2014-2020 (Junta de Andalucia, project I + D + i) A1-FQM-341-UGR18Programa de Ayudas a Proyectos I + D + i destinadas a Universidades y Entidades Publicas de Investigacion (Junta de Andalucia) PY20_0034