High Antimicrobial Activity and Low Human Cell Cytotoxicity of Core–Shell Magnetic Nanoparticles Functionalized with an Antimicrobial Peptide

Abstract

Superparamagnetic iron oxide nanoparticles (SPIONs) functionalized with antimicrobial agents are promising infection-targeted therapeutic platforms when coupled with external magnetic stimuli. These antimicrobial nanoparticles (NPs) may offer advantages in fighting intracellular pathogens as well as biomaterial-associated infections. This requires the development of NPs with high antimicrobial activity without interfering with the biology of mammalian cells. Here, we report the preparation of biocompatible antimicrobial SPION@gold core-shell NPs based on covalent immobilization of the antimicrobial peptide (AMP) cecropin melittin (CM) (the conjugate is named AMP-NP). The minimal inhibitory concentration (MIC) of the AMP-NP for Escherichia coli was 0.4 μg/mL, 10-times lower than the MIC of soluble CM. The antimicrobial activity of CM depends on the length of the spacer between the CM and the NP. AMP-NPs are taken up by endothelial (between 60 and 170 pg of NPs per cell) and macrophage (between 18 and 36 pg of NPs per cell) cells and accumulate preferentially in endolysosomes. These NPs have no significant cytotoxic and pro-inflammatory activities for concentrations up to 200 μg/mL (at least 100 times higher than the MIC of soluble CM). Our results in membrane models suggest that the selectivity of AMP-NPs for bacteria and not eukaryotic membranes is due to their membrane compositions. The AMP-NPs developed here open new opportunities for infection-site targeting.

Cecropin–Melittin Functionalized Polyurethane Surfaces Prevent Staphylococcus epidermidis Adhesion without Inducing Platelet Adhesion and Activation

“…In this work, we demonstrated that these CM–Au NPs, after immobilization onto PU films, were able to add bactericidal properties to PU against S. epidermidis even in the presence of hPlasma. These results are consistent with previous studies in which CM was immobilized onto titanium and glass and tested against several Gram‐positive and Gram‐negative bacteria, attesting the broad spectrum of antimicrobial action retained by CM even when immobilized onto Au NPs. Moreover, CM–Au NPs decrease platelet adhesion and activation to PU, particularly in the presence of hPlasma.…”

“…Moreover, CM–Au NPs decrease platelet adhesion and activation to PU, particularly in the presence of hPlasma. Even though cytotoxicity experiments were not conduct, previous work reported low cytotoxicity against human cells, namely fibroblasts and endothelial cells, confirming the safety of this AMP …”

“…Moreover, CM–SH and PEG immobilization reduced significantly the contact angle, increasing the hydrophilic nature of the surface. This fact could be explained by film functionalization with negative terminated spacers (COOH–PEGs) in combination with cationic CM (rich in arginine amino acids) and spacers (NH 2 –PEGs) that can add to the surface zwitterionic properties . Hydrophilic and zwitterionic surfaces have antifouling properties due to their ability to form a hydration layer.…”

Synthesis, Radiolabelling and In Vitro Imaging of Multifunctional Nanoceramics

“…Cellular uptake of these nanocomposite particles was also conducted using a non‐cancerous fibroblast cell line, FEK‐4, (Figure S34–S38, ESI). No alteration in the morphology of the cells was apparent up to 6 hours after addition, a timescale far exceeding most common cellular imaging experiments in living cells ,. After 4 h incubation, a z‐stacking experiment showed that the NPs are evenly distributed throughout the cytoplasm in addition to adhering to the outer cellular membrane.…”

Design of multifunctional magnetic hybrid silica aerogels with improved properties

“…10a Figure 10a). An increased coercivity observed for all [IOx] doped aerogels at near zero magnetization can be attributed to the increase in interparticle distance of the magnetic cores upon integration with the non-magnetic silica and crosslinker components [44,47] and therefore, the less effective coupling of dipole moments may have occured.…”