Antimicrobial activity and cellular toxicity of nanoparticle–polymyxin B conjugates

Abstract

We investigate the antimicrobial activity and cytotoxicity to mammalian cells of conjugates of the peptide antibiotic polymyxin B (PMB) to Au nanoparticles and CdTe quantum dots. Au nanoparticles fully covered with PMB are identical in antimicrobial activity to the free drug alone, whereas partially-conjugated Au particles show decreased effectiveness in proportion to the concentration of Au. CdTe-PMB conjugates are more toxic to Escherichia coli than PMB alone, resulting in a flattening of the steep PMB dose-response curve. The effect is most pronounced at low concentrations of PMB, with a greater effect on the concentration required to reduce growth by half (IC50) than on the concentration needed to inhibit all growth (minimum inhibitory concentration, MIC). The Gram positive organism Staphylococcus aureus is resistant to both PMB and CdTe, showing minimal increased sensitivity when the two are conjugated. Measurement of reactive oxygen species (ROS) generation shows a significant reduction in photo-generated hydroxyl and superoxide radicals with CdTe-PMB as compared with bare CdTe. There is a corresponding reduction in toxicity of QD-PMB versus bare CdTe to mammalian cells, with nearly 100% survival in fibroblasts exposed to bactericidal concentrations of QD-PMB. The situation in bacteria is more complex: photoexcitation of the CdTe particles plays a small role in IC50 but has a significant effect on the MIC, suggesting that at least two different mechanisms are responsible for the antimicrobial action seen. These results show that it is possible to create antimicrobial agents using concentrations of CdTe quantum dots that do not harm mammalian cells.

CdTe and CdSe Quantum Dots Cytotoxicity: A Comparative Study on Microorganisms

“…The heavy metal damage was observed in Bacillus subtilis incubated with CdSe, however these microorganisms have an extrusion mechanism that enable Gram-positive bacteria to pump out Cadmium ions [77]. Although secondary effects could be detected, such as the membrane depolarization, the most important antibacterial effect of QDs depends on hydroxyl and superoxide radicals produced by the photo-generation of reactive oxygen species [78]. …”

Antifungal activity of gold nanoparticles prepared by solvothermal method

“…The applications of the nanoparticles are mainly due to the quantum size effect, which is the function of the number of free electrons in the nanoparticles [5]. Few reports are also available which show that the gold nanoparticles exhibit good antimicrobial activity [6][7][8]. Their predominant antimicrobial activity can be attributed to the strong cytotoxicity to various bacterial cells.…”

Advances in the Experimental and Theoretical Understandings of Antibiotic Conjugated Gold Nanoparticles for Antibacterial Applications

“…Generally, AuNPs do not exhibit antibacterial property, but due to the presence of unreacted ligands or some ionic impurities, they act as an antibacterial agent . AuNPs can be made antibacterial by grafting hydrophobic molecules, antibacterial peptides, antibiotics and a molecule which makes the gold nanoparticles positively charged . Most often, antibiotic molecules have been used to make the AuNPs antibacterial in nature .…”