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A cell membrane-targeting AIE photosensitizer as a necroptosis inducer for boosting cancer theranostics.

ABSTRACT: The exploration of cellular organelle-specific anchoring photosensitizers with both prominent fluorescence imaging behavior and extraordinary reactive oxygen species (ROS) production capability is highly in demand but remains a severe challenge for effective cancer theranostics involving photodynamic therapy (PDT). In this contribution, we developed a cell membrane-targeting and NIR-emission photosensitizer having an aggregation-induced emission (AIE) tendency. The AIE photosensitizer, namely TBMPEI, is capable of lighting up and ablating cancer cells by means of a necroptosis procedure enabling cell membrane rupture and DNA degradation upon light irradiation, endowing TBMPEI with impressive performance for both in vitro and in vivo fluorescence imaging-guided PDT.

SUBMITTER: Niu N

PROVIDER: S-EPMC9132078 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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A cell membrane-targeting AIE photosensitizer as a necroptosis inducer for boosting cancer theranostics.

Niu Niu N Yu Ying Y Zhang Zhijun Z Kang Miaomiao M Wang Lei L Zhao Zheng Z Wang Dong D Tang Ben Zhong BZ

Chemical science 20220419 20

The exploration of cellular organelle-specific anchoring photosensitizers with both prominent fluorescence imaging behavior and extraordinary reactive oxygen species (ROS) production capability is highly in demand but remains a severe challenge for effective cancer theranostics involving photodynamic therapy (PDT). In this contribution, we developed a cell membrane-targeting and NIR-emission photosensitizer having an aggregation-induced emission (AIE) tendency. The AIE photosensitizer, namely TB ...[more]

PMID: 35685806

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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 cell membrane-targeting AIE photosensitizer as a necroptosis inducer for boosting cancer theranostics.

Publications

A cell membrane-targeting AIE photosensitizer as a necroptosis inducer for boosting cancer theranostics.

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