Light-Activated Biodegradable Covalent Organic Framework-Integrated Heterojunction for Photodynamic, Photothermal, and Gaseous Therapy of Chronic Wound Infection

ACS Appl Mater Interfaces. 2021 Sep 15;13(36):42396-42410. doi: 10.1021/acsami.1c10031. Epub 2021 Sep 2.

Abstract

Chronic wound healing, impeded by bacterial infections and drug resistance, poses a threat to global human health. Antibacterial phototherapy is an effective way to fight microbial infection without causing drug resistance. Covalent organic frameworks (COFs) are a class of highly crystalline functional porous carbon-based materials composed of light atoms (e.g., carbon, nitrogen, oxygen, and borane), showing potential applications in the biomedical field. Herein, we constructed porphyrin-based COF nanosheets (TP-Por CON) for synergizing photodynamic and photothermal therapy under red light irradiation (e.g., 635 nm). Moreover, a nitric oxide (NO) donor molecule, BNN6, was encapsulated into the pore volume of the crystalline porous framework structure to moderately release NO triggered by red light irradiation for realizing gaseous therapy. Therefore, we successfully synthesized a novel TP-Por CON@BNN6-integrated heterojunction for thoroughly killing Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus in vitro. Our research identified that TP-Por CON@BNN6 has favorable biocompatibility and biodegradability, low phototoxicity, anti-inflammatory properties, and excellent mice wound healing ability in vivo. This study indicates that the TP-Por CON@BNN6-integrated heterojunction with multifunctional properties provides a potential strategy for COF-based gaseous therapy and microorganism-infected chronic wound healing.

Keywords: antibacterial activity; covalent organic framework; nitric oxide; photodynamic therapy; photothermal therapy; porphyrin.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / radiation effects
  • Anti-Inflammatory Agents / therapeutic use*
  • Anti-Inflammatory Agents / toxicity
  • Cell Line
  • Escherichia coli / drug effects
  • Light
  • Metal-Organic Frameworks / radiation effects
  • Metal-Organic Frameworks / therapeutic use*
  • Metal-Organic Frameworks / toxicity
  • Mice
  • Mice, Inbred BALB C
  • Nitric Oxide Donors / radiation effects
  • Nitric Oxide Donors / therapeutic use*
  • Nitric Oxide Donors / toxicity
  • Photosensitizing Agents / radiation effects
  • Photosensitizing Agents / therapeutic use*
  • Photosensitizing Agents / toxicity
  • Porphyrins / radiation effects
  • Porphyrins / therapeutic use
  • Porphyrins / toxicity
  • Staphylococcal Skin Infections / drug therapy*
  • Staphylococcus aureus / drug effects
  • Wound Healing / drug effects*

Substances

  • Anti-Inflammatory Agents
  • Metal-Organic Frameworks
  • Nitric Oxide Donors
  • Photosensitizing Agents
  • Porphyrins