Engineering of stealth (maghemite/PLGA)/chitosan (core/shell)/shell nanocomposites with potential applications for combined MRI and hyperthermia against cancer Fernández Álvarez, Fátima Caro, Carlos García García, Gracia García Martín, María Luisa Arias Mediano, José Luis Financial support was provided by grants from the 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 Ministerio de Economia y Competitividad (Spain, CTQ2017-86655-R to Maria Luisa Garcia-Martin). The authors also thank the Nanoimaging Unit, unit U28 of NanBiosis - Infraestructuras Cientifico-Tecnologicas Singulares (ICTS) (Spain), where the relaxivity and MRI experiments were performed. (Maghemite/poly(d,l-lactide-co-glycolide))/chitosan (core/shell)/shell nanoparticles have been prepared reproducibly by nanoprecipitation solvent evaporation plus coacervation (production performance approximate to 45%, average size approximate to 325 nm). Transmission electron microscopy, energy dispersive X-ray spectroscopy, electrophoretic determinations, and X-ray diffraction patterns demonstrated the satisfactory embedment of iron oxide nanocores within the solid polymer matrix and the formation of an external shell of chitosan in the nanostructure. The adequate magnetic responsiveness of the nanocomposites was characterized in vitro by hysteresis cycle determinations and by visualization of the nanosystem under the influence of a 0.4 T permanent magnet. Safety and biocompatibility of the (core/shell)/shell particles were based on in vitro haemocompatibility studies and cytotoxicity tests against HFF-1 human foreskin fibroblasts and on ex vivo toxicity assessments on tissue samples from Balb/c mice. Transversal relaxivities, determined in vitro at a low magnetic field of 1.44 T, demonstrated their capability as T-2 contrast agents for magnetic resonance imaging, being comparable to that of some iron oxide-based contrast agents. Heating properties were evaluated in a high frequency alternating electromagnetic gradient: a constant maximum temperature of approximate to 46 degrees C was generated within approximate to 50 min, while antitumour hyperthermia tests on T-84 colonic adenocarcinoma cells proved the relevant decrease in cell viability (to approximate to 39%) when treated with the nanosystem under the influence of that electromagnetic field. Finally, in vivo magnetic resonance imaging studies and ex vivo histology determinations of iron deposits postulated the efficacy of chitosan to provide long-circulating capabilities to the nanocomposites, retarding nanoparticle recognition by the mononuclear phagocyte system. To our knowledge, this is the first study describing such a type of biocompatible and long-circulating nanoplatform with promising theranostic applications (biomedical imaging and hyperthermia) against cancer. 2021-07-01T11:29:32Z 2021-07-01T11:29:32Z 2021-05-21 info:eu-repo/semantics/article J. Mater. Chem. B, 2021, 9, 4963-4980. DOI: [10.1039/d1tb00354b] http://hdl.handle.net/10481/69461 10.1039/d1tb00354b eng http://creativecommons.org/licenses/by-nc/3.0/es/ info:eu-repo/semantics/openAccess Atribución-NoComercial 3.0 España Royal Society of Chemistry