Embedding Biomimetic Magnetic Nanoparticles Coupled with Peptide AS-48 into PLGA to Treat Intracellular Pathogens
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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, ConcepciónEditorial
MDPI
Materia
BMNPs PLGA AS-48 Photothermia Hyperthermia Magnetic nanoparticles Antimicrobial peptide Monocytes Mycobacterium tuberculosis
Date
2022-12-08Referencia bibliográfica
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]
Sponsorship
FEDER Operational Program; Proyectos de I + D + I, del Plan Andaluz de Investigacion, Desarrollo e Innovacion B-BIO-432-UGR20 B-BIO-268-UGR20 B-CTS-216-UGR20 A-FQM-492-UGR20; Instituto de Salud Carlos III European Commission P20-00346 P20_00339 P20-00233; Spanish Government PI20-01658; Federation of European Microbiological Societies (FEMS) EC2019-005930-P PDC2021-121135.100 FEMS-GO-2020-201Abstract
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.