Erythrocyte-Mimicking Nanovesicle Targeting <i>Porphyromonas gingivalis</i> for Periodontitis.

Abstract

<i>Porphyromonas gingivalis</i> has been demonstrated to have the strongest association with periodontitis. Within the host, <i>P. gingivalis</i> relies on acquiring iron and heme through the aggregation and lysis of erythrocytes, which are important factors in the growth and virulence of <i>P. gingivalis</i>. Additionally, the excess obtained heme is deposited on the surface of <i>P. gingivalis</i>, protecting the cells from oxidative damage. Based on these biological properties of the interaction between <i>P. gingivalis</i> and erythrocytes, this study developed an erythrocyte membrane nanovesicle loaded with gallium porphyrins to mimic erythrocytes. The nanovesicle can target and adhere with <i>P. gingivalis</i> precisely, being lysed and utilized by <i>P. gingivalis</i> as erythrocytes. Ingested gallium porphyrin replaces iron porphyrin in <i>P. gingivalis</i>, causing intracellular metabolic disruption. Deposited porphyrin generates a large amount of reactive oxygen species (ROS) under blue light, causing oxidative damage, and its lethality is enhanced by bacterial metabolic disruption, synergistically killing <i>P. gingivalis</i>. Our results demonstrate that this strategy can target and inhibit <i>P. gingivalis</i>, reduce its invasion of epithelial cells, and alleviate the progression of periodontitis.