A Multifunctional Nanosystem Based on Bacterial Cell-Penetrating Photosensitizer for Fighting Periodontitis Via Combining Photodynamic and Antibiotic Therapies

Abstract

Photodynamic therapy (PDT), an emerging approach that involves photosensitizers, light, and molecular oxygen, has shown promise for fighting periodontitis. However, PDT does not always acquire the desired therapeutic outcomes since some photosensitizers have strong hydrophobic properties and are difficult to absorb efficiently by periodontal pathogenic bacteria. Here, a hydrophobic photosensitizer chlorin e6 (Ce6) was hydrophilically modified via conjugation with TAT peptide, a cationic cell-penetrating peptide, to improve its solubility and enhance its bacterial adsorption by promoting its interaction with the negatively charged cell walls and penetration through the cell membranes. The obtained TAT-Ce6 conjugate (TAT-Ce6) was used to prepare self-assembled nanoparticles (NPs) for loading tinidazole (TDZ), a clinically used antibiotic agent, thus hoping to achieve synergistic antiperiodontitis effects through combining PDT and antibiotic therapy. Compared to free Ce6, TAT-Ce6 nanoparticles (TAT-Ce6 NPs) had greatly enhanced adsorption and penetration abilities for periodontal pathogen bacteria and also exhibited significantly increased PDT efficiencies in both periodontal pathogen bacteria and monocyte macrophages. Upon 635 nm laser irradiation, TDZ-loaded TAT-Ce6 (TAT-Ce6/TDZ) NPs exerted remarkable synergistic antiperiodontitis effects of PDT and antibiotic therapy, reflecting in the effective killing of periodontal pathogenic bacteria in vitro and the reduced adsorption of alveolar bone in the Sprague−Dawley rat model of periodontitis. Altogether, this study develops a novel photosensitizer that can be efficiently absorbed by the periodontal pathogenic bacteria and also provides a potent combination strategy of PDT with antibiotic therapy for clinical periodontitis treatment.

Self-assembled Nanoparticles of Polycationic b Rush and p Hotosensitizer for Synergistic Photothermal and Photodynamic Therapies Against Periodontitis

“…In vivo PTT and PDT performances of sPDMA@ICG NPs A periodontitis animal model was constructed in Sprague Dawley (SD) rats according to our previous method [17]. After anesthetization, the rats were ligated with orthodontic steel wires at the gingival sulcus of the left maxillary second molar and then feed with 10% sucrose water for 4 weeks to induce periodontitis.…”

“…Female Sprague Dawley (SD) rats with average body weight of 150 g were provided by Vital River Laboratory Animal Technology Co., Ltd. (Beijing, China) and were kept in plastic cages with free access to food and water. Periodontitis animal model was constructed in SD rats according to our previous method [17]. After anesthetization, the rats were ligated with orthodontic steel wires at the gingival sulcus of the left maxillary second molar and then feed with 10% sucrose water for 4 weeks to induce periodontitis.…”

“…An increasing number of investigations have been carried out for antimicrobial treatment through PTT and PDT. In a recent report [17], we developed a novel photosensitizer with excellent bacteria penetrating ability and combined PDT and antibiotics for periodontitis treatment by ghting periodontal pathogenic bacteria more e ciently. Some NIR light-absorbing agents exhibit prominent photothermal and photodynamic performances simultaneously.…”

Derivatives of Natural Chlorophylls as Agents for Antimicrobial Photodynamic Therapy

“…Compared to the free chlorin e 6 , the nanoparticles have a significantly better ability to penetrate the cells of periodontal pathogenic bacteria and provide an enhanced efficiency of PDT toward both periodontal pathogenic bacteria and monocyte macrophages. On irradiation with light at a wavelength of 635 nm, the antibiotic-loaded nanoparticles exhibited an efficient combined antimicrobial effect [85].…”

Self-assembled nanoparticles containing photosensitizer and polycationic brush for synergistic photothermal and photodynamic therapy against periodontitis

“…An increasing number of investigations have been carried out for antimicrobial treatment through PTT and PDT. In a recent report [ 21 ], we developed a novel photosensitizer with excellent bacteria penetrating ability and combined PDT and antibiotics for periodontitis treatment by fighting periodontal pathogenic bacteria more efficiently.…”