Antimicrobial peptide-targeted photodynamic therapy for preventing periodontal plaque biofilm formation through the disruption of quorum sensing system

Owing to high rates of antibiotic resistance, the elimination of periodontal plaque biofilms has become a significant clinical challenge. In this context, metal–organic framework (MOF)-based photodynamic therapy (PDT) has emerged as a novel antimicrobial treatment option. However, this therapeutic s...

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Main Authors: Wen Li, Fengqun You, Jie Yang, Deao Gu, Yuyang Li, Xuan Zhang, Leiying Miao, Weibin Sun
Format: Article
Language:English
Published: Elsevier 2025-08-01
Series:Materials Today Bio
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Online Access:http://www.sciencedirect.com/science/article/pii/S259000642500540X
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author Wen Li
Fengqun You
Jie Yang
Deao Gu
Yuyang Li
Xuan Zhang
Leiying Miao
Weibin Sun
author_facet Wen Li
Fengqun You
Jie Yang
Deao Gu
Yuyang Li
Xuan Zhang
Leiying Miao
Weibin Sun
author_sort Wen Li
collection DOAJ
description Owing to high rates of antibiotic resistance, the elimination of periodontal plaque biofilms has become a significant clinical challenge. In this context, metal–organic framework (MOF)-based photodynamic therapy (PDT) has emerged as a novel antimicrobial treatment option. However, this therapeutic strategy suffers from drawbacks such as the insufficient generation of reactive oxygen species and the lack of targeted biofilm clearance, which greatly hinder its clinical application. Here, a multifunctional MOF-based nanocomposite (ICG@Uio-66-UBI) was developed by modifying MOFs (Uio-66-NH2) with an antimicrobial peptide (UBI29-41) to enhance PDT efficiency. Our findings showed that the UBI29-41 targets EPS and selectively binds to lipopolysaccharide (LPS) on bacterial surfaces via electrostatic interactions, enabling precise delivery of ICG-generated ROS under 808-nm near-infrared irradiation, which disrupts bacterial membranes and inhibits biofilm formation. Subsequently, UBI29-41 blocks LPS-TLR4 binding, suppressing NF-κB signaling and reducing pro-inflammatory cytokine production. Furthermore, the nanocomposite significantly downregulates the LuxS/AI-2 quorum sensing (QS) system, reducing AI-2 synthesis and virulence gene expression, thereby inhibiting biofilm formation. In vivo studies confirmed the platform's efficacy in inhibiting biofilm formation and preventing collagen degradation in gingival tissue. By synergistically combining targeted antimicrobial action, anti-inflammatory effects, and QS modulation, ICG@Uio-66-UBI represents a breakthrough in precision periodontal therapy, offering a potent solution for biofilm-associated infections.
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spelling doaj-art-132a0b0808a54879bf00f72ac338d9e52025-08-20T03:15:06ZengElsevierMaterials Today Bio2590-00642025-08-013310197010.1016/j.mtbio.2025.101970Antimicrobial peptide-targeted photodynamic therapy for preventing periodontal plaque biofilm formation through the disruption of quorum sensing systemWen Li0Fengqun You1Jie Yang2Deao Gu3Yuyang Li4Xuan Zhang5Leiying Miao6Weibin Sun7Department of Endodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, ChinaShanghai Aiyou Biotechnology Center, Shanghai, ChinaDepartment of Periodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, ChinaDepartment of Orthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, ChinaDepartment of Prosthodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, ChinaDepartment of Periodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, ChinaDepartment of Endodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China; Corresponding author. Department of Endodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University, No.30 Zhongyang Road, Xuanwu District, Nanjing, Jiangsu Province, China.Department of Periodontics, Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Research Institute of Stomatology, Nanjing University, Nanjing, China; Corresponding author. Department of Periodontics, Nanjing Stomatological Hospital , Affiliated Hospital of Medical School, Nanjing University, No.30 Zhongyang Road, Xuanwu District, Nanjing, Jiangsu Province, China.Owing to high rates of antibiotic resistance, the elimination of periodontal plaque biofilms has become a significant clinical challenge. In this context, metal–organic framework (MOF)-based photodynamic therapy (PDT) has emerged as a novel antimicrobial treatment option. However, this therapeutic strategy suffers from drawbacks such as the insufficient generation of reactive oxygen species and the lack of targeted biofilm clearance, which greatly hinder its clinical application. Here, a multifunctional MOF-based nanocomposite (ICG@Uio-66-UBI) was developed by modifying MOFs (Uio-66-NH2) with an antimicrobial peptide (UBI29-41) to enhance PDT efficiency. Our findings showed that the UBI29-41 targets EPS and selectively binds to lipopolysaccharide (LPS) on bacterial surfaces via electrostatic interactions, enabling precise delivery of ICG-generated ROS under 808-nm near-infrared irradiation, which disrupts bacterial membranes and inhibits biofilm formation. Subsequently, UBI29-41 blocks LPS-TLR4 binding, suppressing NF-κB signaling and reducing pro-inflammatory cytokine production. Furthermore, the nanocomposite significantly downregulates the LuxS/AI-2 quorum sensing (QS) system, reducing AI-2 synthesis and virulence gene expression, thereby inhibiting biofilm formation. In vivo studies confirmed the platform's efficacy in inhibiting biofilm formation and preventing collagen degradation in gingival tissue. By synergistically combining targeted antimicrobial action, anti-inflammatory effects, and QS modulation, ICG@Uio-66-UBI represents a breakthrough in precision periodontal therapy, offering a potent solution for biofilm-associated infections.http://www.sciencedirect.com/science/article/pii/S259000642500540XMetal–organic frameworksPhotodynamic therapyAntimicrobial peptidesInhibiting biofilms formationLuxS/AI-2
spellingShingle Wen Li
Fengqun You
Jie Yang
Deao Gu
Yuyang Li
Xuan Zhang
Leiying Miao
Weibin Sun
Antimicrobial peptide-targeted photodynamic therapy for preventing periodontal plaque biofilm formation through the disruption of quorum sensing system
Materials Today Bio
Metal–organic frameworks
Photodynamic therapy
Antimicrobial peptides
Inhibiting biofilms formation
LuxS/AI-2
title Antimicrobial peptide-targeted photodynamic therapy for preventing periodontal plaque biofilm formation through the disruption of quorum sensing system
title_full Antimicrobial peptide-targeted photodynamic therapy for preventing periodontal plaque biofilm formation through the disruption of quorum sensing system
title_fullStr Antimicrobial peptide-targeted photodynamic therapy for preventing periodontal plaque biofilm formation through the disruption of quorum sensing system
title_full_unstemmed Antimicrobial peptide-targeted photodynamic therapy for preventing periodontal plaque biofilm formation through the disruption of quorum sensing system
title_short Antimicrobial peptide-targeted photodynamic therapy for preventing periodontal plaque biofilm formation through the disruption of quorum sensing system
title_sort antimicrobial peptide targeted photodynamic therapy for preventing periodontal plaque biofilm formation through the disruption of quorum sensing system
topic Metal–organic frameworks
Photodynamic therapy
Antimicrobial peptides
Inhibiting biofilms formation
LuxS/AI-2
url http://www.sciencedirect.com/science/article/pii/S259000642500540X
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