Due to their good mechanical stability compared to gelatin, collagen or polyethylene glycol nanofibers and slow degradation rate, biodegradable poly-ε-caprolactone (PCL) nanofibers are promising material as scaffolds for bone and soft-tissue engineering. Here, PCL nanofibers were prepared by the electrospinning method and then subjected to surface functionalization aimed at improving their biocompatibility and bioactivity. For surface modification, two approaches were used: (i) COOH-containing polymer was deposited on the PCL surface using atmospheric pressure plasma copolymerization of CO 2 and C 2 H 4 , and (ii) PCL nanofibers were coated with multifunctional bioactive nanostructured TiCaPCON film by magnetron sputtering of TiC-CaO-Ti 3 PO x target. To evaluate bone regeneration ability in vitro, the surface-modified PCL nanofibers were immersed in simulated body fluid (SBF, 1×) for 21 days. The results obtained indicate different osteoblastic and epithelial cell response depending on the modification method. The TiCaPCON-coated PCL nanofibers exhibited enhanced adhesion and proliferation of MC3T3-E1 cells, promoted the formation of Ca-based mineralized layer in SBF and, therefore, can be considered as promising material for bone tissue regeneration. The PCL-COOH nanofibers demonstrated improved adhesion and proliferation of IAR-2 cells, which shows their high potential for skin reparation and wound dressing.
In recent years, bacteria inactivation during their direct physical contact with surface nanotopography has become one of the promising strategies for fighting infection. Contact-killing ability has been reported for several nanostructured surfaces, e.g., black silicon, carbon nanotubes, zinc oxide nanorods, and copper oxide nanosheets. Herein, we demonstrate that Gramnegative antibiotic-resistant Escherichia coli (E. coli) bacteria are killed as a result of their physical destruction while contacting nanostructured h-BN surfaces. BN films, made of spherical nanoparticles formed by numerous nanosheets and nanoneedles with a thickness <15 nm, have been obtained through a reaction of ammonia with amorphous boron. The contact-killing bactericidal effect of BN nanostructures has been compared with a toxic effect of gentamicin released from them. For a wider protection against bacterial and fungal infection, the films have been saturated with a mixture of gentamicin and amphotericin B. Such BN films demonstrate a high antibiotic/antimycotic agent loading capacity and a fast initial and sustained release of therapeutic agents for 170−260 h depending on the loaded dose. The pristine BN films possess high antibacterial activity against E. coli K-261 strain at their initial concentration of 10 4 cells/mL, attaining >99% inactivation of colony forming units after 24 h, same as gentamicin-loaded (150 μg/cm 2 ) BN sample. The BN films loaded with a mixture of gentamicin (150 and 300 μg/cm 2 ) and amphotericin B (100 μg/ cm 2 ) effectively inhibit the growth of E. coli K-261 and Neurospora crassa strains. During immersion in the normal saline solution, the BN film generates reactive oxygen species (ROS), which can lead to accelerated oxidative stress at the site of physical cell damage. The obtained results are valuable for further development of nanostructured surfaces having contact killing, ROS, and biocide release abilities.
Drug-loaded nanocarriers have a great potential for tumor therapy. Such systems must have high drug-loading efficacy in an alkaline medium and effectively release therapeutic agent in an acidic medium of endosomal/ lysosomal compartments of tumor cells. Herein, we experimentally and theoretically (using density functional theory) studied the chemical interaction of doxorubicin (DOX) with different boron nitride (BN) surfaces depending on the degree of their oxidation. Three groups of hexagonal BN nanoparticles (BNNPs) obtained by boron oxide chemical vapor deposition process, i.e., (i) as-synthesized and those after (ii) repeated washing in water and (iii) high-temperature annealing, and their corresponding DOX−BN conjugates were studied. Oxidation of BNNPs significantly improved their interaction with DOX. As a result, the amount of immobilized DOX on the B 2 O 3 surface was higher in comparison with the BNNPs containing little oxygen. The formation of stable DOX−BN conjugates mainly depended on the attraction of electron density in the area of aromatic rings in the highest occupied molecular orbital of DOX. The presence of a protonated NH 2 groups in DOX can facilitate electron density transfer from the DOXH + to the boron oxide surface.
Utilization of antibacterial components-conjugated
nanoparticles
(NPs) is emerging as an attractive strategy for combating various
pathogens. Herein, we demonstrate that Ag/BN NPs and antibiotic-loaded
BN and Ag/BN nanoconjugates are promising carriers to fight bacterial
and fungal infections. Extensive biological tests included two types
of Gram-positive methicillin-resistant Staphylococcus
aureus strains (B8469 and MW2), two types of Gram-negative Pseudomonas aeruginosa strains (ATCC27853 and B1307/17),
and 47 types of Escherichia coli strains
(including 41 multidrug-resistant ones), as well as five types of
fungal cultures: Candida albicans (candidiasis-thrush)
ATCC90028 and ATCC24433, Candida parapsilosis ATCC90018, Candida auris CBS109113, and Neurospora crassa
wt. We have demonstrated
that, even within a single genus Escherichia, there
are many hospital E. coli strains with
multi-drug resistance to different antibiotics. Gentamicin-loaded
BN NPs have high bactericidal activity against S. aureu
s, P. aeruginosa,
and 38 types of the E. coli strains.
For the rest of the tested E. coli strains, the Ag
nanoparticle-containing nanohybrids have shown superior bactericidal
efficiency. The Ag/BN nanohybrids and amphotericin B-loaded BN and
Ag/BN NPs also reveal high fungicidal activity against C. albicans, C. auris, C. parapsilosis, and N. crassa cells. In addition, based on the density functional theory calculations,
the nature of antibiotic-nanoparticle interaction, the sorption capacity
of the BN and Ag/BN nanohybrids for gentamicin and amphotericin B,
and the most energetically favorable positions of the drug molecules
relative to the carrier surface, which lead to lowest binding energies,
have been determined. The obtained results clearly show high therapeutic
potential of the antibiotic-loaded Ag/BN nanocarriers providing a
broad bactericidal and fungicidal protection against all of the studied
pathogens.
A new low-pressure plasma-based approach to activate the surface of BN nanoparticles (BNNPs) in order to facilitate the attachment of folate acid (FA) molecules for cancer-specific therapy is described. Plasma treatment of BNNPs (BNNPs PT ) was performed in a radiofrequency plasma reactor using ethylene and carbon dioxide monomers. The carboxyl groups deposited on the surface of BNNPs PT were activated by N,N'-dicyclohexylcarbodiimide (DCC) and participated in the condensation reaction with ethylene diamine (EDA) to form a thin amino-containing layer (EDA-BNNP PT ). Then, the DCC-activated FA was covalently bonded with BNNPs PT by a chemical reaction between amino groups of EDA-BNNPs PT and carboxyl groups of FA. Density functional theory calculations showed that the pre-activation of FA by DCC is required for grafting of the FA to the EDA-BNNPs PT . It was also demonstrated that after FA immobilization, the electronic characteristics of the pteridine ring remain unchanged, indicating that the targeting properties of the FA/EDA-BNNPs PT nanohybrids are preserved.Author Contributions: E.S.P. performed NH 2 -functionalization and FA conjugation, as well as obtained FT ICR MS spectrum and prepared the manuscript, L.Y.A. and P.B.S. performed simulations and described the results, P.V.K.-K. carried out plasma surface polymerization, A.M.K. fabricated BN nanoparticles by CVD and performed SEM and EDS spectroscopy characterization, J.P. and A.M. obtained XPS spectra and performed their analysis, K.Y.G. performed FTIR spectroscopy, D.V.S. analyzed the results and edited the manuscript.
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