Chitas Rute, Nunes Cláudia, Reis Salette, Parreira Paula, Martins Maria Cristina L
i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal.
INEB-Instituto de Engenharia Biomédica, Universidade do Porto, 4200-135 Porto, Portugal.
Pharmaceutics. 2022 Dec 8;14(12):2745. doi: 10.3390/pharmaceutics14122745.
The major risk factor associated with the development of gastric cancer is chronic infection with . The available treatments, based on a cocktail of antibiotics, fail in up to 40% of patients and disrupt their gut microbiota. The potential of blank nanostructured lipid carriers (NLC) for eradication was previously demonstrated by us. However, the effect of NLC charge, size and protein corona on -specific bactericidal activity herein studied was unknown at that time. All developed NLC formulations proved bactericidal against . Although cationic NLC had 10-fold higher bactericidal activity than anionic NLC, they lacked specificity, since was also affected. Anionic NLC achieved complete clearance in both morphologies (rod- and coccoid-shape) by inducing alterations in bacteria membranes and the cytoplasm, as visualized by transmission electron microscopy (TEM). The presence of an NLC protein corona, composed of 93% albumin, was confirmed by mass spectrometry. This protein corona delayed the bactericidal activity of anionic NLC against and hindered NLC activity against . Overall, these results sustain the use of NLC as a promising antibiotic-free strategy targeting .
与胃癌发生相关的主要风险因素是幽门螺杆菌的慢性感染。现有的基于抗生素组合的治疗方法,在高达40%的患者中无效,并会破坏他们的肠道微生物群。我们之前已经证明了空白纳米结构脂质载体(NLC)对幽门螺杆菌根除的潜力。然而,当时在此研究中NLC电荷、大小和蛋白质冠层对幽门螺杆菌特异性杀菌活性的影响尚不清楚。所有开发的NLC制剂都被证明对幽门螺杆菌有杀菌作用。尽管阳离子NLC的杀菌活性比阴离子NLC高10倍,但它们缺乏特异性,因为其他细菌也受到影响。阴离子NLC通过诱导细菌膜和细胞质的改变,在两种形态(杆状和球状)中都实现了完全清除,这通过透射电子显微镜(TEM)观察到。通过质谱法确认了由93%白蛋白组成的NLC蛋白质冠层的存在。这种蛋白质冠层延迟了阴离子NLC对幽门螺杆菌的杀菌活性,并阻碍了NLC对其他细菌的活性。总体而言,这些结果支持将NLC作为一种有前景的针对幽门螺杆菌的无抗生素策略。