Bactericidal activity and biocompatibility of ceragenin-coated magnetic nanoparticles.
BACKGROUND
Ceragenins, synthetic mimics of endogenous antibacterial peptides, are promising candidate antimicrobial agents. However, in some settings their strong bactericidal activity is associated with toxicity towards host cells. To modulate ceragenin CSA-13 antibacterial activity and biocompatibility, CSA-13-coated magnetic nanoparticles (MNP-CSA-13) were synthesized. Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to characterize MNP-CSA-13 physicochemical properties. Bactericidal action and ability of these new compounds to prevent Pseudomonas. aeruginosa biofilm formation were assessed using a bacteria killing assay and crystal violet staining, respectively. Release of hemoglobin from human red blood cells was measured to evaluate MNP-CSA-13 hemolytic activity. In addition, we used surface activity measurements to monitor CSA-13 release from the MNP shell. Zeta potentials of P. aeruginosa cells and MNP-CSA-13 were determined to assess the interactions between the bacteria and nanoparticles. Morphology of P. aeruginosa subjected to MNP-CSA-13 treatment was evaluated using atomic force microscopy (AFM) to determine structural changes indicative of bactericidal activity.


RESULTS
Our studies revealed that the MNP-CSA-13 nanosystem is stable and may be used as a pH control system to release CSA-13. MNP-CSA-13 exhibits strong antibacterial activity, and the ability to prevent bacteria biofilm formation in different body fluids. Additionally, a significant decrease in CSA-13 hemolytic activity was observed when the molecule was immobilized on the nanoparticle surface.


CONCLUSIONS
Our results demonstrate that CSA-13 retains bactericidal activity when immobilized on a MNP while biocompatibility increases when CSA-13 is covalently attached to the nanoparticle.
Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2c, 15-222, Bialystok, Poland. mikro.nano@umb.edu.pl.
Katarzyna
K
Niemirowicz
Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2c, 15-222, Bialystok, Poland. urszula.surel@umb.edu.pl.
Urszula
U
Surel
Institute of Chemistry, University of Bialystok, 1 Hurtowa, 15-399, Bialystok, Poland. agawilcz@uwb.edu.pl.
Agnieszka Z
AZ
Wilczewska
Department of Materials and Biomedical Engineering, Białystok University of Technology, 15-351, Białystok, Poland. j.mystkowska@pb.edu.pl.
Joanna
J
Mystkowska
Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2c, 15-222, Bialystok, Poland. ewelina.piktel@wp.pl.
Ewelina
E
Piktel
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA. guxbo1@gmail.com.
Xiaobo
X
Gu
Department of Physiology, Medical University of Białystok, 15-230, Białystok, Poland. namiotz@poczta.onet.pl.
Zbigniew
Z
Namiot
Department of Neurology, Medical University of Bialystok, 15-230, Bialystok, Poland. alakul@umb.edu.pl.
Alina
A
Kułakowska
Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT, USA. paul_savage@byu.edu.
Paul B
PB
Savage
Department of Microbiological and Nanobiomedical Engineering, Medical University of Bialystok, Mickiewicza 2c, 15-222, Bialystok, Poland. buckirobert@gmail.com.|Department of Physiology, Pathophysiology and Microbiology of Infections, The Faculty of Health Sciences of the Jan Kochanowski University in Kielce, 25-317, Kielce, Poland. buckirobert@gmail.com.
Robert
R
Bucki
D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects; D002152:Calorimetry, Differential Scanning; D004912:Erythrocytes / Q000187:drug effects; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D046529:Microscopy, Electron, Transmission; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D017550:Spectroscopy, Fourier Transform Infrared; D013256:Steroids / Q000737:chemistry* / Q000494:pharmacology; D013818:Thermogravimetry
D000900:Anti-Bacterial Agents; D058185:Magnetite Nanoparticles; D013256:Steroids; C521528:ceragenin CSA-13