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Antimicrobial activity and cellular toxicity of nanoparticle-polymyxin B conjugates

机译：纳米颗粒-多粘菌素B缀合物的抗菌活性和细胞毒性

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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 Escherichiacoli 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 Staphylococcusaureus 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.
机译：我们研究了抗菌素活性肽多肽多粘菌素B（PMB）对金纳米颗粒和CdTe量子点的缀合物对哺乳动物细胞的抗菌活性和细胞毒性。完全被PMB覆盖的Au纳米颗粒与单独的游离药物具有相同的抗菌活性，而部分结合的Au颗粒则与Au的浓度成比例地降低了有效性。 CdTe-PMB共轭物比单独的PMB对大肠杆菌的毒性更大，导致陡峭的PMB剂量反应曲线趋于平坦。在低浓度的PMB上效果最明显，对抑制生长所需的浓度（IC50）的影响要大于抑制所有生长所需的浓度（最小抑制浓度MIC）。革兰氏阳性生物葡萄球菌对PMB和CdTe均具有抗性，当两者结合时，其敏感性增加最小。活性氧（ROS）生成的测量表明，与裸露的CdTe相比，CdTe-PMB显着降低了光生羟基和超氧化物自由基。与裸露的CdTe相比，QD-PMB对哺乳动物细胞的毒性相应降低，暴露于QD-PMB杀菌浓度的成纤维细胞存活率接近100％。细菌中的情况更为复杂：CdTe颗粒的光激发在IC50中起很小的作用，但对MIC却有显着影响，这表明所观察到的抗菌作用至少有两种不同的机制。这些结果表明，可以使用不会损害哺乳动物细胞的浓度的CdTe量子点来产生抗菌剂。

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