Metal–Organic‐Framework‐Based Hydrogen‐Release Platform for MultieffectiveHelicobacter PyloriTargeting Therapy and Intestinal Flora Protective Capabilities

Abstract

urea into ammonia to increase the pH around thallus to resist the destruction of gastric acid, which is also one essential cause for colonizing in the gastric mucosa chronically. [2] The virulence factors generated by H. pylori can directly act on gastric mucosa, which stimulate mucosal cells, neutrophils and macrophages to secrete plenty of inflammatory chemokines, thereby inducting severe mucosal inflammatory reactions. [3] Furthermore, activated inflammatory cells would produce excessive oxygen free radicals through respiration, leading to mitochondrial damage and protein denaturation of gastric mucosal epithelial cells, thereby causing oxidativestress-mediated gastric mucosal disruption, which further resulting in gastric diseases, such as chronic gastritis and peptic ulcer. [4] Nowadays, the antibiotic therapy dominated by clarithromycin, metronidazole or amoxicillin is used as the first-line treatment for H. pylori in the world. [5] However, for the lack of targeting property on H. pylori, the long-term use of antibiotics tends to destroy the homeostasis of intestinal flora. [6] Furthermore, although antibiotics can destroy H. pylori, it is still a formidable challenge of antibiotics to address the dysregulation of inflammation response and the impaired gastric mucosa. Therefore, it is urgent to develop a new antibiotic replacement therapy to achieve the following three requirements: I. Targeting inflammation precisely and eliminating H. pylori effectively. II. Regulating hyperactive immunoreaction and repairing damaged gastric mucosa. III. Protecting intestinal flora.Herein, we have designed a metal-organic framework hydrogen-generation system (Pd(H) @ ZIF-8 @ AP) that is formed by a hydrogen-generation nanoparticle based on a metalorganic framework (Pd(H) @ ZIF-8) and the negatively charged ascorbate palmitate (AP) hydrogel (Scheme 1a), which has three advantages (Scheme 1b): I) Inflammation-targeting and multiple antibacterial properties. It has been reported that longterm colonization of H. pylori leads to chronic gastric mucosal inflammation, [7] accompanied by increased expression of positively charged proteins and matrix metalloproteinase (MMP, IV collagenase), resulting in positive charge in the inflammatory site. [8] Therefore, AP hydrogel with both negative charge Helicobacter pylori (H. pylori) infection is the leading cause of chronic gastritis, peptic ulcer, and gastric cancer. Antibiotics, as traditional method for eliminating H. pylori, have no targeting effect, which causes serious bacterial resistance and gut dysbacteriosis. Moreover, antibiotics can hardly address hyperactive inflammatory response or damaged gastric mucosal barrier caused by H. pylori infection. Here, a pH-responsive metal-organic framework hydrogen-generation nanoparticle (Pd(H) @ ZIF-8) is reported, which is encapsulated with ascorbate palmitate (AP) hydrogel. Both in vitro and in vivo experiments demonstrate that the outer AP hydrogel can target and adhere to the inflammatory site through electrostatic interactions,...

Nanomaterial-Based Zinc Ion Interference Therapy to Combat Bacterial Infections

“…Gastritis caused by Helicobacter pylori is a very serious problem that might lead to gastric cancer (95,96). Due to the gastric acid microenvironment and the unique physiological state of the gastric inflammation site, Zhang et al (75) developed a pH-responsive Zn(II) MOF hydrogen-generation system (Pd(H)@ZIF-8@AP). The Pd(H)@ZIF-8@AP was further coated by negatively charged ascorbyl palmitate (AP) hydrogel for targeting the H. pylori infection site (Figure 3A).…”

“… Helicobacter pylori treatment. (A, B) Schematic diagram showing the process of H pylori and restoring impaired gastric mucosa ( 75 ). Copyright 2021, WILEY-VCH.…”

“…To further improve Zn(II) release and enhance the therapeutic effects of Zn(II), dual stimulus-responsive nanodelivery systems ( 99 ) have been aggressively explored. The pH-responsive ( 75 ) and light-triggered ZIF-8 could accomplish enhanced drug release in spatial control and/or temporal control manner. It could respond to two physical stimuli to trigger drug release at the exact spot.…”

Cosmetic-Derived Mannosylerythritol Lipid-B-Phospholipid Nanoliposome: An Acid-Stabilized Carrier for Efficient Gastromucosal Delivery of Amoxicillin for In Vivo Treatment of Helicobacter pylori

“…Histological assessment using H & E staining ( Figure 5 c) indicated obvious pathological changes in the gastric mucosa of the PBS group compared with the healthy group, which manifested as highly abnormal hyperplasia composed of irregular glands with complex structural changes (red circle), and a large number of inflammatory cell infiltrates (red arrows), similar to findings reported in a previous study. 38 In contrast, gastric mucosal inflammation was slightly reduced after the administration of free amoxicillin. However, gastric mucosa inflammation disappeared after the LipoSC-MELB4/AMX administration, and there was no significant histological difference between LipoSC-MELB4/AMX-treated mice and mice in the healthy group.…”

“…Fluorescence staining for Occludin-1 and ZO-1 proteins was performed to assess the integrity of the gastric mucosa in fresh gastric tissue. 38 …”