Antimicrobial activity and cellular toxicity of nanoparticle–polymyxin B conjugates

Abstract

We investigate the antimicrobial activity and cytotoxicity to mammalian cells of conjugatesof the peptide antibiotic polymyxin B (PMB) to Au nanoparticles and CdTe quantumdots. Au nanoparticles fully covered with PMB are identical in antimicrobialactivity to the free drug alone, whereas partially-conjugated Au particles showdecreased effectiveness in proportion to the concentration of Au. CdTe–PMBconjugates are more toxic to Escherichia coli than PMB alone, resulting in a flatteningof the steep PMB dose–response curve. The effect is most pronounced at lowconcentrations of PMB, with a greater effect on the concentration required toreduce growth by half (IC50) than on the concentration needed to inhibit allgrowth (minimum inhibitory concentration, MIC). The Gram positive organismStaphylococcus aureus is resistant to both PMB and CdTe, showing minimal increasedsensitivity when the two are conjugated. Measurement of reactive oxygen species(ROS) generation shows a significant reduction in photo-generated hydroxyl andsuperoxide radicals with CdTe–PMB as compared with bare CdTe. There is acorresponding reduction in toxicity of QD–PMB versus bare CdTe to mammalian cells,with nearly 100% survival in fibroblasts exposed to bactericidal concentrations ofQD–PMB. The situation in bacteria is more complex: photoexcitation of theCdTe 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 antimicrobialaction seen. These results show that it is possible to create antimicrobial agentsusing concentrations of CdTe quantum dots that do not harm mammalian cells.