Reactive Oxygen\nSpecies-Responsive Pillararene-Embedded\nCovalent Organic Frameworks with Amplified Antimicrobial Photodynamic\nTherapy for the Targeted Elimination of Periodontitis Pathogens

Reactive oxygen species (ROS)-responsive drug delivery\nsystems\npossess immense potential for targeted delivery and controlled release\nof therapeutics. However, the rapid responsiveness to ROS and sustained\nrelease of antibacterial drugs are often limited by the challenging\nmicroenvironment of periodontitis. Integrating ROS-responsive drug\ndelivery systems with photocatalytic technologies presents a strategic\napproach to overcome these limitations. Herein, a pillararene-embedded\ncovalent organic framework (PCOF) incorporating the antibacterial\nprodrug thioacetal (TA) has been developed to treat periodontitis.\nThis drug-loaded nanoplatform, namely TA-loaded PCOF, utilizes the\nself-amplifying ROS property to enhance therapeutic efficacy. PCOFs\ndemonstrate exceptional photosensitivity and ROS generation capabilities\nwhen employed as drug carriers. When exposed to ROS, TA within the\nnanoplatform was activated and cleaved into cinnamaldehyde (CA), a\nhighly potent antibacterial compound. By leveraging visible light\nto activate the site-specific infection targeting, TA-loaded PCOF\neffectively alleviated periodontitis, thereby advancing the field\nof antibacterial drug delivery systems.