Protonated Charge Reversal Nanodrugs for Active Targeting Clearance of Helicobacter Pylori Accompanied by Gut Microbiota Protection

Abstract

Helicobacter pylori (H. pylori) is listed as a definite carcinogen and clinical triple therapy is less satisfactory because H. pylori colonizes beneath the gastric mucous layer and easily forms biofilm. More importantly, the frequent and excessive use of antibiotics causes a disorder of gut microbiota due to the lack of targeting to H. pylori. Here, a kind of protonated charge reversal metal based nanodrugs (MNDs)—ZnO‐Ag‐mercaptoacetamide@chitosan for H. pylori eradication treatment without affecting beneficial gut microbiota is prepared. In H. pylori infected mouse model, the MNDs actively target submucosa colonized H. pylori owing to mucous penetrability and protonation effect, and further eradicate H. pylori and its biofilm by producing metal ions and reactive oxygen species. Transcriptomic analysis shows that there are no obvious side effects to intestinal microorganisms during the treatment. Besides, it is found that the MNDs are great potential to remove gastric inflammation along with the blocking of inflammatory pathways and the reduction of virulence factors, which is related to the infiltration of CD4+ T cells to clear H. pylori.

Future Nanotechnology‐Based Strategies for Improved Management of Helicobacter pylori Infection

“…The potential in vivo utility of a multifuntional mucoadhesive system based on chitosan was recently examined in a work by Liu et al. [ 249 ] In this article, the authors indicated that a protonated charged reversal metal‐based nano‐construction namely ZnO‐Ag‐mercaptoacetamide incorporated with chitosan could be a helpful nanosystem to precisely target H. pylori bacteria. The success of this approach could be attributed to four important reasons.…”

“…Although this excellent study was an example of an advanced approach in the arsenal against mucoadhesive and also mucopenetrative H. pylori bacteria, the nano‐DDS used by Liu et al. [ 249 ] did not address the need to kill H. pylori bacteria which were localized inside the gastric cell cytosol. The importance of mucoinert and cytoadhesive nanostructures in the battle against mucopenetrated and internalized H. pylori is discussed in the following sections.…”

Bimetallic Nanozyme: A Credible Tag for In Situ-Catalyzed Reporter Deposition in the Lateral Flow Immunoassay for Ultrasensitive Cancer Diagnosis

“…Metal-based nanozymes have been favored in fields such as immunoassays, biosensing, and therapy due to their unique electronic properties, good biocompatibility, and chemical stability. − Bimetallic nanozymes can be synthesized as random or ordered alloys, core–shell structures, or even Janus-like particles. They have been reported to exhibit excellent enzyme-like activity presumably due to the synergistic or additive effects. − The catalytic constant ( K cat ) of bimetallic nanozymes is 2–3 orders of magnitude higher than that of natural horseradish peroxidase (HRP). , Therefore, bimetallic nanozymes have been considered as a promising material for greatly enhancing detection sensitivity .…”