Nanoantibiotics containing membrane-active human cathelicidin LL-37 or synthetic ceragenins attached to the surface of magnetic nanoparticles as novel and innovative therapeutic tools: current status and potential future applications

Abstract

Nanotechnology-based therapeutic approaches have attracted attention of scientists, in particular due to the special features of nanomaterials, such as adequate biocompatibility, ability to improve therapeutic efficiency of incorporated drugs and to limit their adverse effects. Among a variety of reported nanomaterials for biomedical applications, metal and metal oxide-based nanoparticles offer unique physicochemical properties allowing their use in combination with conventional antimicrobials and as magnetic field-controlled drug delivery nanocarriers. An ever-growing number of studies demonstrate that by combining magnetic nanoparticles with membrane-active, natural human cathelicidin-derived LL-37 peptide, and its synthetic mimics such as ceragenins, innovative nanoagents might be developed. Between others, they demonstrate high clinical potential as antimicrobial, anti-cancer, immunomodulatory and regenerative agents. Due to continuous research, knowledge on pleiotropic character of natural antibacterial peptides and their mimics is growing, and it is justifying to stay that the therapeutic potential of nanosystems containing membrane active compounds has not been exhausted yet.

<p>NDM-1 Carbapenemase-Producing Enterobacteriaceae are Highly Susceptible to Ceragenins CSA-13, CSA-44, and CSA-131</p>

“…Therefore, CSAs can be considered as a new approach to eradicate MDR pathogens. 16,20,29,38,39 Moreover, bacteria are unable to achieve high levels of resistance to CSAs. It should be pointed out that ceragenins appear to be well tolerated and exhibits no degradation in the presence of bacterial and host proteases, making these properties a significant area of the antimicrobial research.…”

“…15 The molecular architecture of ceragenins is founded on a cholic acid, which is appended by amine groups, therefore ceragenins are also known as cationic steroid antimicrobials (CSAs). 16 Describing in more detail, CSAs demonstrate positive charges arranged on one face and hydrophobic residues on the other. 17 The mechanism of the bactericidal action proposed for these compounds comprises an electrostatic connection between ceragenins and the negatively charged molecules of the bacterial surface.…”

“…This association enables the further direct and rapid antimicrobial activity of CSAs resulting in the microbial membrane insertion, ultimately leading to changes in the membrane organization of phospholipids and sudden membrane depolarization. 16 This affinity of CSAs for bacterial membrane components is due to the cell selectivity. The recent data showed that the study compounds selectively associate with prokaryotes over eukaryotic cells, which possibly arises from the higher net of the negative charge present on prokaryotic membranes.…”

“…18 The therapeutic appropriateness of ceragenins has been emphasized by multiple publications. 16 CSAs are assumed to be a promising alternative to conventional antibiotics due to a broad spectrum of their activity against potent microbial pathogens, such as Gram-positive and Gramnegative bacteria as well as fungi and, importantly, MDR strains. 15,16,19 What is more, the development of resistance to CSAs is considerably lower compared to conventional antibiotics.…”

“…15,16,19 What is more, the development of resistance to CSAs is considerably lower compared to conventional antibiotics. 16 So far, no bacteria have accomplished high levels of resistance to ceragenins. 20 Apart from antibacterial effects, these molecules also display antibiofilm, sporicidal, antiviral, antiparasitic, and anticancer activities.…”