Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085, India.
Homi Bhabha National Institute, Anushaktinagar, Mumbai 400094, India.
ACS Appl Bio Mater. 2024 Oct 21;7(10):6958-6969. doi: 10.1021/acsabm.4c01041. Epub 2024 Sep 27.
Bacterial infection is one of the major concerns of the growing society, and over the years, different permutations and combinations of various drugs and adjuvants have been attempted, which led to considerable improvements in the efficacy of the antibacterial drugs. In this regard, macrocyclic receptors such as cyclodextrin, cucurbiturils, calixarene, etc., have played a major role by modulating the drug properties that supplement the antibacterial efficacy. In this study, we have developed cucurbit[7]uril (CB7)-functionalized Au nanoparticles (CB7AuNPs) to modulate the activity of an antibiotic, levofloxacin (LOFL). From the spectroscopic and thermodynamic changes in the LOFL, it has been established that two of the prototropic forms, LOFLH and LOFLH, form strong 1:1 host/guest complexes with CB7/CB7AuNP. Both these interactions led to significant upward shifts in the p values as well as photostability of LOFL, thereby enhancing the availability of the active form for the antibacterial activity, at the physiological pH. Further, the LOFL uptake has also been established on CB7AuNP, which retained the CB7-LOFL activity at very low concentration of the CB7 host, functionalized on AuNP. Detailed antibacterial studies of LOFL, both as complexed with CB7 and CB7AuNP, were carried out using four food-borne pathogens (, , and ), which revealed a creditable enhancement in the antibacterial property, irrespective of the bacterium strain. These results are quite promising at this stage for the development of drugs customized for multidrug-resistant bacteria.
细菌感染是日益发展的社会面临的主要问题之一。多年来，人们尝试了不同的药物和佐剂的排列组合，这使得抗菌药物的疗效有了显著提高。在这方面，诸如环糊精、瓜环、杯芳烃等大环受体通过调节药物性质来提高抗菌药物的疗效，从而发挥了重要作用。在这项研究中，我们开发了葫芦脲（CB7）功能化的金纳米粒子（CB7AuNPs）来调节抗生素左氧氟沙星（LOFL）的活性。通过 LOFL 的光谱和热力学变化，已经确定 LOFL 的两种质子化形式，即 LOFLH 和 LOFLH，与 CB7/CB7AuNP 形成强的 1:1 主客体配合物。这两种相互作用都导致 LOFL 的 p 值以及光稳定性显著升高，从而在生理 pH 值下增加了活性形式的可用性，提高了其抗菌活性。此外，还在 CB7AuNP 上建立了 LOFL 的摄取，这使得在 CB7 作为金纳米粒子的配体的浓度非常低的情况下，仍保留了 CB7-LOFL 的活性。使用四种食源性病原体（、、和）进行了 LOFL 的详细抗菌研究，结果表明，无论是哪种细菌菌株，其抗菌性能都有显著提高。在现阶段，这些结果为开发针对多药耐药菌的药物非常有前景。
