Treatment of periodontitis with simulated red blood cell nanovesicles targeting Porphyromonas gingivalis

This article is selected:Porphyromonas gingivalis has been proved to have the strongest correlation with periodontitis. In the host, Porphyromonas gingivalis relies on the aggregation and lysis of red blood cells to obtain iron and heme, which is an important factor for the growth and virulence of Porphyromonas gingivalis. In addition, the excess heme was deposited on the surface of Porphyromonas gingivalis to protect cells from oxidative damage. Based on these biological characteristics of the interaction between Porphyromonas gingivalis and red blood cells, a nanovesicle loaded with gallium porphyrin was developed to simulate red blood cells. Nano-vesicles can accurately target and adhere to Porphyromonas gingivalis, and are cleaved by Porphyromonas gingivalis and used as red blood cells. The ingested gallium porphyrin replaced the iron porphyrin in Porphyromonas gingivalis, which led to the disorder of intracellular metabolism. The deposited porphyrin produced a large amount of reactive oxygen species (ROS) under blue light, which caused oxidative damage, and its lethality was enhanced by destroying bacterial metabolism, killing Porphyromonas gingivalis cooperatively. Our results show that this strategy can target and inhibit Porphyromonas gingivalis, reduce its invasion of epithelial cells, and alleviate the progress of periodontitis.

Innovations: 1. Based on the special biological interaction mechanism between Porphyromonas gingivalis and red blood cells, the targeted nano-vesicle therapy strategy was developed for the first time; 2. Innovative use of gallium porphyrin molecules to simulate the metabolic characteristics of red blood cells and accurately interfere with the living environment of bacteria; 3. Combined with photodynamic therapy and metabolic interference, construct multiple synergistic sterilization mechanism; 4. Using biomimetic method to improve the targeting and specificity of nanocarriers. Scientific research inspiration: 1. Thoroughly analyze the complex mechanism of interaction between microorganisms and host cells, and provide new ideas for precision medicine; 2. Understand the microbial-host interaction from the perspective of biological evolution and ecosystem, and explore more intelligent treatment strategies; 3. Inspire the design of drug delivery system by learning from the camouflage and imitation mechanism in the evolution of nature; 4. Emphasize the principle of "individualized treatment" and pertinence in microbial treatment, and break through the "one size fits all" treatment mode. 

Extension of ideas: 1. Extend this strategy to other bacterial diseases with iron metabolism as the key; 2. Combined with artificial intelligence technology, predict and design more accurate nano-biological carriers; 3. Deeply study the metabolic characteristics of different types of bacteria, and develop more targeted therapy strategies; 4. Combining gene editing technology to further improve the accuracy and functionality of nanocarriers; 5. Develop multifunctional nanocarriers and integrate the functions of diagnosis, treatment and monitoring; 6. Explore the potential therapeutic strategies of microbial regulation in chronic inflammatory diseases; 7. Build a more complex biomimetic nano-system to simulate a more elaborate biological interaction mechanism.

DOI : 10.1021/acsnano.4c02316