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A H₂ S-Generated Supramolecular Photosensitizer for Enhanced Photodynamic Antibacterial Infection and Relieving Inflammation.

ABSTRACT: Photodynamic therapy (PDT) is a promising treatment against bacteria-caused infections. By producing large amounts of reactive oxygen species (ROS), PDT can effectively eliminate pathogenic bacteria, without causing drug resistance. However, excessive ROS may also impose an oxidative stress on surrounding tissues, resulting in local inflammation. To avoid this major drawback and limit pro-inflammation during PDT, this work prepared a supramolecular photosensitizer (TPP-CN/CP5) based on host-guest interactions between a cysteine-responsive cyano-tetraphenylporphyrin (TPP-CN) and a water-soluble carboxylatopillar[5]arene (CP5). TPP-CN/CP5 not only possesses excellent photodynamic antibacterial properties, but also shows good anti-inflammatory and cell protection capabilities. Under 660 nm light irradiation, TPP-CN/CP5 could rapidly produce abundant ROS for sterilization. After the PDT process, the addition of cysteine (Cys) triggers the release of H₂ S from TPP-CN. H₂ S then stops the induced inflammation by inhibiting the production of related inflammatory factors. Both in vitro and in vivo experiments show the excellent antibacterial effects and anti-inflammatory abilities of TPP-CN/CP5. These results will certainly promote the clinical application of PDT in the treatment of bacterial infectious diseases.

SUBMITTER: Tian J

PROVIDER: S-EPMC10916657 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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A H<sub>2</sub> S-Generated Supramolecular Photosensitizer for Enhanced Photodynamic Antibacterial Infection and Relieving Inflammation.

Tian Jia J Huang Baoxuan B Xia Lei L Zhu Yucheng Y Zhang Weian W

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20231214 9

Photodynamic therapy (PDT) is a promising treatment against bacteria-caused infections. By producing large amounts of reactive oxygen species (ROS), PDT can effectively eliminate pathogenic bacteria, without causing drug resistance. However, excessive ROS may also impose an oxidative stress on surrounding tissues, resulting in local inflammation. To avoid this major drawback and limit pro-inflammation during PDT, this work prepared a supramolecular photosensitizer (TPP-CN/CP5) based on host-gues ...[more]

PMID: 38095436

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Project description:The noninvasive nature of photodynamic therapy (PDT) enables the preservation of organ function in cancer patients. However, PDT is impeded by hypoxia in the tumor microenvironment (TME) caused by high intracellular oxygen (O2) consumption and distorted tumor blood vessels. Therefore, increasing oxygen generation in the TME would be a promising methodology for enhancing PDT. Herein, we proposed a concept of ferroptosis-promoted PDT based on the biochemical characteristics of cellular ferroptosis, which improved the PDT efficacy significantly by producing reactive oxygen species (ROS) and supplying O2 sustainably through the Fenton reaction. In contrast to traditional strategies that increase O2 based on decomposition of limited concentration of hydrogen peroxide (H2O2), our methodology could maintain the concentration of H2O2 and O2 through the Fenton reaction. Methods: For its association with sensitivity to ferroptosis, solute carrier family 7 member 11 (SLC7A11) expression was characterized by bioinformatics analysis and immunohistochemistry of oral tongue squamous cell carcinoma (OTSCC) specimens. Afterwards, the photosensitizer chlorin e6 (Ce6) and the ferroptosis inducer erastin were self-assembled into a novel supramolecular Ce6-erastin nanodrug through hydrogen bonding and π-π stacking. Then, the obtained Ce6-erastin was extensively characterized and its anti-tumor efficacy towards OTSCC was evaluated both in vitro and in vivo. Results: SLC7A11 expression is found to be upregulated in OTSCC, which is a potential target for ferroptosis-mediated OTSCC treatment. Ce6-erastin nanoparticles exhibited low cytotoxicity to normal tissues. More significantly, The over-accumulated intracellular ROS, increased O2 concentration and inhibited SLC7A11 expression lead to enhanced toxicity to CAL-27 cells and satisfactory antitumor effects to xenograft tumour mouse model upon irradiation. Conclusion: Our ferroptosis promoted PDT approach markedly enhances anticancer actions by relieving hypoxia and promoting ROS production, thereby our work provides a new approach for overcoming hypoxia-associated resistance of PDT in cancer treatment.

Dataset Information

A H₂ S-Generated Supramolecular Photosensitizer for Enhanced Photodynamic Antibacterial Infection and Relieving Inflammation.

Publications

A H<sub>2</sub> S-Generated Supramolecular Photosensitizer for Enhanced Photodynamic Antibacterial Infection and Relieving Inflammation.

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A H2 S-Generated Supramolecular Photosensitizer for Enhanced Photodynamic Antibacterial Infection and Relieving Inflammation.

Publications

A H<sub>2</sub> S-Generated Supramolecular Photosensitizer for Enhanced Photodynamic Antibacterial Infection and Relieving Inflammation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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A H₂ S-Generated Supramolecular Photosensitizer for Enhanced Photodynamic Antibacterial Infection and Relieving Inflammation.