Fullerenol Nanoparticles Eradicate Helicobacter pylori via pH-Responsive Peroxidase Activity

Abstract

Helicobacter pylori (H. pylori) eradication by antibiotics and proton pump inhibitor treatment is limited by the low pH microenvironment in the stomach and can lead to antibiotic resistance. We fabricated fullerenol nanoparticles (FNPs) with varied chemical structures responding to a pinacol rearrangement of vicinal hydroxyl to form carbonyls in low pH environments. An obvious increase in CO/C−O was induced in low pH and was positively correlated with a peroxidase-like activity. The FNPs exerted an excellent effect on H. pylori eradication in vitro and in vivo because of their peroxidase-like activity. FNP treatment of a H. pylori biofilm revealed that FNPs broke down polysaccharides in cell wall components, resulting in collapse of the bacteria. The cycles of FNPs combining and dissociating with the peroxidase substrate were detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and confirmed that FNPs enhance peroxidase-like activity. Further, the isothermal titration calorimetry results showed that FNPs with more CO/C−O had greater affinity to bind the peroxidase substrates. Therefore, we suggest that varied CO/ C−O serves as a switch to respond to low pH in the stomach to kill H. pylori by inducing a peroxidase-like activity. FNPs can also overcome the challenge of antibiotic resistance to achieve H. pylori eradication in the stomach.

Nanocluster Mediated Photothermia Improves Eradication Efficiency and Antibiotic Sensitivity of Helicobacter Pylori

“…Despite the potential of PTT in antibacterial use, its non-speci c heat damage to nearby tissues is potentially concerning. Unlike intracellular hyperthermia of tumors when internalization of nanoparticles into cells is crucial [40], it is important to avoid adjacent tissue damage during antibacterial applications. This will require prevention of individual nanoparticles being endocytosed by gastrointestinal mucosa cells.…”

“…Declining eradication rates of H. pylori worldwide related to antimicrobial resistance have inspired a switch from antibiotic-based regimens to novel therapeutic strategies such as nanoparticle-based approaches. In recent years, nanomaterials have exhibited great potential in the growth inhibition of H. pylori [39,40]. Besides, the photothermal anti-H. pylori effect of nanomaterials was evaluated effectively in vitro and in vivo [41].…”

Carbon Nanomaterials (CNMs) and Enzymes: From Nanozymes to CNM-Enzyme Conjugates and Biodegradation

“…In a recent report, fullerene derivatives were applied to this end through the presentation of multiple functional groups inspired from the natural enzymes’ catalytic sites [ 344 ]. Analogously to the other CNMs, fullerenes could also act as peroxidase mimics at acidic pH, and were thus envisaged for the eradication of Helycobacter pylori in vivo [ 345 ].…”

Fullerenol protects cornea from ultraviolet B exposure

“…And apart from the activity mentioned above, fullerenol induces endogenous phase II antioxidant enzymes and modulates cell antioxidant status through upregulation of the Nrf/ARE-antioxidant pathway under oxidative stress stimulation [ 22 ]. Moreover, recent studies have shed light on the excellent peroxidase-like activities that fullerenol nanoparticles exhibit by the cycles of combining and dissociating with the peroxidase substrate in low pH environments [ 27 ]. Unlike other ROS scavengers, fullerenol also exhibits high stability in various physiological environments or under different kinds of irradiation stimuli.…”