Enhanced Cytotoxic Effect of TAT–PLGA-Embedded DOXO Carried by Biomimetic Magnetic Nanoparticles upon Combination with Magnetic Hyperthermia and Photothermia Jabalera Ruz, Ylenia María Sola Leyva, Alberto Carrasco Jiménez, María Paz Iglesias Salto, Guillermo Ramón Jiménez López, Concepción Phothermia Hyperthermia BMNPs PLGA Magnetic nanoparticles TAT peptide Doxorubicin This research work was supported by the Ministerio de Economia y Competitividad (CGL2016-76723), the Ministerio de Ciencia e Innovacion (PID2019-109294RB-100) projects, Ramon y Cajal program (RYC-2014-16901), the Junta de Andalucia Programa Operativo FEDER 2014-2020 (A1-FQM-341-UGR18, C-FQM-497-UGR18, A-BIO-376-UGR18), and the Proyectos de I + D + I, del Plan Andaluz de Investigacion, Desarrollo e Innovacion (P20_00208 and P20_00346). This research was also aided by the Andalusian regional government (CTS-236) and by the FUR (Fondo Unico della Ricerca, University of Verona)of Dr. M. Perduca. Alberto Sola-Leyva holds a Formacion de Doctores 2018 grant (ref. PRE2018-085440) from the Ministerio de Ciencia, Innovacion, y Universidades (Spain). Ylenia Jabalera wants to acknowledge an FPU2016 grant (ref. FPU16_04580) from the Ministerio de Educacion, Ciencia, y Deporte y Competitividad (Spain). The synergy between directed chemotherapy and thermal therapy (both magnetic hyperthermia and photothermia) mediated by a nanoassembly composed of functionalized biomimetic magnetic nanoparticles (BMNPs) with the chemotherapeutic drug doxorubicin (DOXO) covered by the polymer poly(lactic-co-glycolic acid) (PLGA), decorated with TAT peptide (here referred to as TAT–PLGA(DOXO-BMNPs)) is explored in the present study. The rationale behind this nanoassembly lies in an optimization of the nanoformulation DOXO-BMNPs, already demonstrated to be more efficient against tumor cells, both in vitro and in vivo, than systemic traditional therapies. By embedding DOXO-BMNPs into PLGA, which is further functionalized with the cell-penetrating TAT peptide, the resulting nanoassembly is able to mediate drug transport (using DOXO as a drug model) and behaves as a hyperthermic agent (induced by an alternating magnetic field (AMF) or by laser irradiation with a laser power density of 2 W/cm2). Our results obtained using the HepG2 cell line show that there is a synergy between chemotherapy and thermal therapy that results in a stronger cytotoxic effect when compared to that caused by the soluble DOXO. This is probably due to the enhanced DOXO release occurring upon the application of the thermal therapy, as well as the induced local temperature rise mediated by BMNPs in the nanoassembly following exposition to AMF or to near-infrared (NIR) laser irradiation. These results represent a proof of concept demonstrating that TAT–PLGA(DOXO-BMNPs) can be used to efficiently combine therapies against tumor cells, which is a step forward in the transition from systemic to local treatments. 2021-10-08T06:35:09Z 2021-10-08T06:35:09Z 2021-07-28 journal article Jabalera, Y... [et al.]. Enhanced Cytotoxic Effect of TAT–PLGA-Embedded DOXO Carried by Biomimetic Magnetic Nanoparticles upon Combination with Magnetic Hyperthermia and Photothermia. Pharmaceutics 2021, 13, 1168. [https://doi.org/10.3390/pharmaceutics13081168] http://hdl.handle.net/10481/70731 10.3390/pharmaceutics13081168 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España MDPI