ROS-Responsive Iodine-Embedded Cyclodextrin Nanoplatform for Multipurpose Periodontitis Therapy

Periodontitis, an inflammatory disorder driven by microbial dysbiosis, is featured as elevated reactive oxygen species (ROS) and dysregulated inflammation, leading to tissue destruction and alveolar bone resorption. A promising therapeutic approach involves antimicrobial actions with ROS neutralization. Addressing the clinical limitation of elemental iodine (I 2 ) to topical use, we engineered a ROS-scavenging covalent cyclodextrin framework (CCF) embedding I 2 to confer dual functionality for periodontitis treatment. Initially, potassium iodide cyclodextrin metal-organic framework (KI-CD-MOF) was synthesized, which was then cross-linked with oxalyl chloride to introduce a ROS-scavenging peroxalate ester bond. Simultaneously, the iodide ions in KI-CD-MOF were oxidized to I 2 , which was integrated throughout the framework. The resulting I 2 -CCF particles had a cubic morphology (300–500 nm) and an I 2 content of 1.03±0.45 %, exhibiting an outstanding biosafety profile, strong bactericidal effectiveness, and significant ROS elimination capability. In vitro , I 2 -CCF downregulated the expression of pro-inflammatory factors TNF-α and IL-1β, while promoting the secretion of anti-inflammatory markers IL-10 and Arg-1. Crucially, in a rodent periodontitis model, I 2 -CCF effectively suppressed dental plaque accumulation, reduced periodontal inflammation, and limited alveolar bone resorption. This work establishes I 2 -CCF as a multipurpose nanotherapeutic that concurrently targets the infectious and oxidative components of periodontitis, offering a potent alternative to conventional treatments.