Reactive Oxygen Species-Responsive Pillararene-Embedded Covalent Organic Frameworks with Amplified Antimicrobial Photodynamic Therapy for the Targeted Elimination of Periodontitis Pathogens

Nano Lett. 2024 Oct 30;24(43):13708-13717. doi: 10.1021/acs.nanolett.4c03788. Epub 2024 Oct 17.

Abstract

Reactive oxygen species (ROS)-responsive drug delivery systems possess immense potential for targeted delivery and controlled release of therapeutics. However, the rapid responsiveness to ROS and sustained release of antibacterial drugs are often limited by the challenging microenvironment of periodontitis. Integrating ROS-responsive drug delivery systems with photocatalytic technologies presents a strategic approach to overcome these limitations. Herein, a pillararene-embedded covalent organic framework (PCOF) incorporating the antibacterial prodrug thioacetal (TA) has been developed to treat periodontitis. This drug-loaded nanoplatform, namely TA-loaded PCOF, utilizes the self-amplifying ROS property to enhance therapeutic efficacy. PCOFs demonstrate exceptional photosensitivity and ROS generation capabilities when employed as drug carriers. When exposed to ROS, TA within the nanoplatform was activated and cleaved into cinnamaldehyde (CA), a highly potent antibacterial compound. By leveraging visible light to activate the site-specific infection targeting, TA-loaded PCOF effectively alleviated periodontitis, thereby advancing the field of antibacterial drug delivery systems.

Keywords: antibacterial materials; covalent organic frameworks; drug delivery systems; pillararene; porous materials.

MeSH terms

  • Acrolein / analogs & derivatives
  • Animals
  • Anti-Bacterial Agents* / chemistry
  • Anti-Bacterial Agents* / pharmacology
  • Anti-Bacterial Agents* / therapeutic use
  • Drug Carriers / chemistry
  • Drug Delivery Systems
  • Humans
  • Metal-Organic Frameworks / chemistry
  • Metal-Organic Frameworks / pharmacology
  • Mice
  • Periodontitis* / drug therapy
  • Periodontitis* / microbiology
  • Photochemotherapy* / methods
  • Prodrugs / chemistry
  • Prodrugs / pharmacology
  • Prodrugs / therapeutic use
  • Reactive Oxygen Species* / metabolism

Substances

  • Reactive Oxygen Species
  • Anti-Bacterial Agents
  • Drug Carriers
  • Metal-Organic Frameworks
  • Prodrugs
  • cinnamaldehyde
  • Acrolein