Embedding Biomimetic Magnetic Nanoparticles Coupled with Peptide AS-48 into PLGA to Treat Intracellular Pathogens Calogero Gaglio, Salvatore Jabalera Ruz, Ylenia María Montalbán López, Manuel Lázaro Callejón, Marina Maqueda Abreu, Mercedes Carrasco Jiménez, María Paz Laso, Alejandro Iglesias Salto, Guillermo Ramón Jiménez López, Concepción BMNPs PLGA AS-48 Photothermia Hyperthermia Magnetic nanoparticles Antimicrobial peptide Monocytes Mycobacterium tuberculosis Among the strategies employed to overcome the development of multidrug-resistant bacteria, directed chemotherapy combined with local therapies (e.g., magnetic hyperthermia) has gained great interest. A nano-assembly coupling the antimicrobial peptide AS-48 to biomimetic magnetic nanoparticles (AS-48-BMNPs) was demonstrated to have potent bactericidal effects on both Gram-positive and Gram-negative bacteria when the antimicrobial activity of the peptide was combined with magnetic hyperthermia. Nevertheless, intracellular pathogens remain challenging due to the difficulty of the drug reaching the bacterium. Thus, improving the cellular uptake of the nanocarrier is crucial for the success of the treatment. In the present study, we demonstrate the embedding cellular uptake of the original nano-assembly into THP-1, reducing the toxicity of AS-48 toward healthy THP-1 cells. We optimized the design of PLGA[AS-48-BMNPs] in terms of size, colloidal stability, and hyperthermia activity (either magnetic or photothermal). The stability of the nano-formulation at physiological pH values was evaluated by studying the AS-48 release at this pH value. The influence of pH and hyperthermia on the AS-48 release from the nano-formulation was also studied. These results show a slower AS-48 release from PLGA[AS-48-BMNPs] compared to previous nano-formulations, which could make this new nano-formulation suitable for longer extended treatments of intracellular pathogens. PLGA[AS-48-BMNPs] are internalized in THP-1 cells where AS-48 is liberated slowly, which may be useful to treat diseases and prevent infection caused by intracellular pathogens. The treatment will be more efficient combined with hyperthermia or photothermia. 2023-01-31T08:44:40Z 2023-01-31T08:44:40Z 2022-12-08 journal article Gaglio, S.C... [et al.]. Embedding Biomimetic Magnetic Nanoparticles Coupled with Peptide AS-48 into PLGA to Treat Intracellular Pathogens. Pharmaceutics 2022, 14, 2744. [https://doi.org/10.3390/pharmaceutics14122744] https://hdl.handle.net/10481/79462 10.3390/pharmaceutics14122744 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional MDPI