Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles Vurro, Federica Jabalera Ruz, Ylenia María Sola Leyva, Alberto Iglesias Salto, Guillermo Ramón Carrasco Jiménez, María Paz Biomimetic magnetic nanoparticles Poly (lactic-co-glycolic) acid PLGA Penetrating TAT peptide Nanoparticles Magnetic Hyperthermia Cellular uptake This research was funded by the FUR (Fondo Unico della Ricerca—University of Verona) of M. Perduca. C.J.-L. acknowledges funding from projects CGL2016-76723 from the Ministerio de Economía y Competitividad from Spain and Fondo Europeo de Desarrollo Regional (FEDER) and Programa Operativo FEDER 2014–2020 (A-BIO-376-UGR18) Junta de Andalucia. M.P.C.-J. acknowledges funding from projects PID2019-109294RB-100 from the Ministerio de Ciencia e Innovación from Spain. We are grateful to the “Centro Piattaforme Tecnologiche” of the University of Verona for giving access to DLS equipment. CJL acknowledges. the Unidad Cientıfica de Excelencia UCE PP 2016.05 (U. Granada) and Instituto de Biotecnología. Y.J. wants to acknowledge a FPU2016 grant (ref. FPU16_04580) from the Ministerio de Educación, Ciencia y Deporte y Competitividad (Spain). AS-L is funded by the Spanish Ministry of Science, Innovation and Universities: Formación de Doctores 2018 (ref. PRE2018-0854409). Thanks go to the Scientific Instrumentation Center (CIC) personnel of the University of Granada for technical assistance with the TEM.We also thank Salvatore Calogero Gaglio for his help in preparing Figure S4. Magnetococcus marinus magnetosome-associated protein MamC, expressed as recombinant, has been proven to mediate the formation of novel biomimetic magnetic nanoparticles (BMNPs) that are successful drug nanocarriers for targeted chemotherapy and hyperthermia agents. These BMNPs present several advantages over inorganic magnetic nanoparticles, such as larger sizes that allow the former to have larger magnetic moment per particle, and an isoelectric point at acidic pH values, which allows both the stable functionalization of BMNPs at physiological pH value and the molecule release at acidic (tumor) environments, simply based on electrostatic interactions. However, difficulties for BMNPs cell internalization still hold back the efficiency of these nanoparticles as drug nanocarriers and hyperthermia agents. In the present study we explore the enhanced BMNPs internalization following upon their encapsulation by poly (lactic-co-glycolic) acid (PLGA), a Food and Drug Administration (FDA) approved molecule. Internalization is further optimized by the functionalization of the nanoformulation with the cell-penetrating TAT peptide (TATp). Our results evidence that cells treated with the nanoformulation [TAT-PLGA(BMNPs)] show up to 80% more iron internalized (after 72 h) compared to that of cells treated with BMNPs (40%), without any significant decrease in cell viability. This nanoformulation showing optimal internalization is further characterized. In particular, the present manuscript demonstrates that neither its magnetic properties nor its performance as a hyperthermia agent are significantly altered due to the encapsulation. In vitro experiments demonstrate that, following upon the application of an alternating magnetic field on U87MG cells treated with BMNPs and TAT-PLGA(BMNPs), the cytotoxic effect of BMNPs was not affected by the TAT-PLGA enveloping. Based on that, difficulties shown in previous studies related to poor cell uptake of BMNPs can be overcome by the novel nanoassembly described here. 2021-04-26T06:50:47Z 2021-04-26T06:50:47Z 2021-03-18 journal article Vurro, F.; Jabalera, Y.; Mannucci, S.; Glorani, G.; Sola-Leyva, A.; Gerosa, M.; Romeo, A.; Romanelli, M.G.; Malatesta, M.; Calderan, L.; et al. Improving the Cellular Uptake of Biomimetic Magnetic Nanoparticles. Nanomaterials 2021, 11, 766. [https://doi.org/10.3390/nano11030766] http://hdl.handle.net/10481/68097 10.3390/nano11030766 eng http://creativecommons.org/licenses/by/3.0/es/ open access Atribución 3.0 España MDPI