Embedding Biomimetic Magnetic Nanoparticles Coupled with Peptide AS-48 into PLGA to Treat Intracellular Pathogens
Salvatore Calogero Gaglio,
Ylenia Jabalera,
Manuel Montalbán-López,
Ana Cristina Millán-Placer,
Marina Lázaro-Callejón,
Mercedes Maqueda,
María Paz Carrasco-Jimenez,
Alejandro Laso,
José A. Aínsa,
Guillermo R. Iglesias,
Massimiliano Perduca,
Concepción Jiménez López
Affiliations
Salvatore Calogero Gaglio
Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134 Verona, Italy
Ylenia Jabalera
Department of Microbiology, Faculty of Sciences, University of Granada, 18071 Granada, Spain
Manuel Montalbán-López
Department of Microbiology, Faculty of Sciences, University of Granada, 18071 Granada, Spain
Ana Cristina Millán-Placer
Departamento de Microbiología, Pediatría, Radiología y Salud Publica (Facultad de Medicina) & BIFI, Universidad de Zaragoza, 50009 Zaragoza, Spain
Marina Lázaro-Callejón
Department of Applied Physics and Instituto de Investigación Biosanitaria ibs. GRANADA, NanoMag Laboratory, University of Granada, 18071 Granada, Spain
Mercedes Maqueda
Department of Microbiology, Faculty of Sciences, University of Granada, 18071 Granada, Spain
María Paz Carrasco-Jimenez
Department of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, Spain
Alejandro Laso
Department of Biochemistry and Molecular Biology I, University of Granada, 18071 Granada, Spain
José A. Aínsa
Departamento de Microbiología, Pediatría, Radiología y Salud Publica (Facultad de Medicina) & BIFI, Universidad de Zaragoza, 50009 Zaragoza, Spain
Guillermo R. Iglesias
Department of Applied Physics and Instituto de Investigación Biosanitaria ibs. GRANADA, NanoMag Laboratory, University of Granada, 18071 Granada, Spain
Massimiliano Perduca
Department of Biotechnology, University of Verona, Strada Le Grazie 15, 37134 Verona, Italy
Concepción Jiménez López
Department of Microbiology, Faculty of Sciences, University of Granada, 18071 Granada, Spain
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.
