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Ferroptosis Promotes Photodynamic Therapy: Supramolecular Photosensitizer-Inducer Nanodrug for Enhanced Cancer Treatment

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 (O(2)) consumption and distorted tumor blood vessels. Therefore, increasing o...

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Autores principales: Zhu, Ting, Shi, Leilei, Yu, Chunyang, Dong, Yabing, Qiu, Feng, Shen, Lingyue, Qian, Qiuhui, Zhou, Guoyu, Zhu, Xinyuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567978/
https://www.ncbi.nlm.nih.gov/pubmed/31244955
http://dx.doi.org/10.7150/thno.32867
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author Zhu, Ting
Shi, Leilei
Yu, Chunyang
Dong, Yabing
Qiu, Feng
Shen, Lingyue
Qian, Qiuhui
Zhou, Guoyu
Zhu, Xinyuan
author_facet Zhu, Ting
Shi, Leilei
Yu, Chunyang
Dong, Yabing
Qiu, Feng
Shen, Lingyue
Qian, Qiuhui
Zhou, Guoyu
Zhu, Xinyuan
author_sort Zhu, Ting
collection PubMed
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 (O(2)) 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 O(2) sustainably through the Fenton reaction. In contrast to traditional strategies that increase O(2) based on decomposition of limited concentration of hydrogen peroxide (H(2)O(2)), our methodology could maintain the concentration of H(2)O(2) and O(2) 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 O(2) 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.
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spelling pubmed-65679782019-06-26 Ferroptosis Promotes Photodynamic Therapy: Supramolecular Photosensitizer-Inducer Nanodrug for Enhanced Cancer Treatment Zhu, Ting Shi, Leilei Yu, Chunyang Dong, Yabing Qiu, Feng Shen, Lingyue Qian, Qiuhui Zhou, Guoyu Zhu, Xinyuan Theranostics Research Paper 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 (O(2)) 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 O(2) sustainably through the Fenton reaction. In contrast to traditional strategies that increase O(2) based on decomposition of limited concentration of hydrogen peroxide (H(2)O(2)), our methodology could maintain the concentration of H(2)O(2) and O(2) 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 O(2) 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. Ivyspring International Publisher 2019-05-18 /pmc/articles/PMC6567978/ /pubmed/31244955 http://dx.doi.org/10.7150/thno.32867 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Zhu, Ting
Shi, Leilei
Yu, Chunyang
Dong, Yabing
Qiu, Feng
Shen, Lingyue
Qian, Qiuhui
Zhou, Guoyu
Zhu, Xinyuan
Ferroptosis Promotes Photodynamic Therapy: Supramolecular Photosensitizer-Inducer Nanodrug for Enhanced Cancer Treatment
title Ferroptosis Promotes Photodynamic Therapy: Supramolecular Photosensitizer-Inducer Nanodrug for Enhanced Cancer Treatment
title_full Ferroptosis Promotes Photodynamic Therapy: Supramolecular Photosensitizer-Inducer Nanodrug for Enhanced Cancer Treatment
title_fullStr Ferroptosis Promotes Photodynamic Therapy: Supramolecular Photosensitizer-Inducer Nanodrug for Enhanced Cancer Treatment
title_full_unstemmed Ferroptosis Promotes Photodynamic Therapy: Supramolecular Photosensitizer-Inducer Nanodrug for Enhanced Cancer Treatment
title_short Ferroptosis Promotes Photodynamic Therapy: Supramolecular Photosensitizer-Inducer Nanodrug for Enhanced Cancer Treatment
title_sort ferroptosis promotes photodynamic therapy: supramolecular photosensitizer-inducer nanodrug for enhanced cancer treatment
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567978/
https://www.ncbi.nlm.nih.gov/pubmed/31244955
http://dx.doi.org/10.7150/thno.32867
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