Helicobacter pylori and Gastric Cancer: A Potential New Paradigm of 3R (Remove, Remodel, Repair) Integrated Therapy Based on Nanomaterials

Helicobacter pylori infection represents a significant modifiable risk factor in the pathogenesis of gastric cancer. Nevertheless, conventional antibiotic treatments have increasingly proven inadequate due to challenges such as antibiotic resistance, microbial dysbiosis, and mucosal damage. In response to these issues, this review introduces an innovative intervention strategy based on the “nanotechnology-based 3R” approach (Remove H. pylori, Remodel the microenvironment, Repair the gastrointestinal tract), which aims to offer a comprehensive solution for managing H. pylori infection. This strategy comprises three principal components. Firstly, the utilization of pH/light/magnetic multi-responsive nanomaterials facilitates the precise eradication of the pathogen and its biofilm. Secondly, to address bacterial immune evasion, these nanomaterials are engineered to target and neutralize virulence factors such as VacA, thereby contributing to the reversal of the local immunosuppressive environment. Thirdly, the utilization of nanomaterials presents a promising approach for the concurrent repair of the mucosal barrier and the maintenance of intestinal microbiome homeostasis. Finally, this paper provides a comprehensive analysis of the specific mechanisms employed by typical nanomaterials, including metal-organic frameworks, charge-reversal nanoparticles, nanozymes, and antimicrobial peptide crystals. These mechanisms involve targeted microbial eradication, activation of autophagy, and the upregulation of tight junction proteins. Furthermore, the study delves into the critical roles played by multimodal external field stimulation and material–host interaction network analysis, which are essential for future clinical translation. Ultimately, this review suggests a potential roadmap for system-precision intervention that transcends the conventional “sterilization first” paradigm. Nonetheless, the current evidence regarding the efficacy and safety of this approach is predominantly derived from cell and mouse models. Therefore, its clinical applicability requires validation through studies involving large animal models and prospective clinical trials.