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Conformational regulation: A new strategy to tunning the ROS generation efficiency of polythiophene-based sonosensitizer.

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Title: Conformational regulation: A new strategy to tunning the ROS generation efficiency of polythiophene-based sonosensitizer.
Authors: Tang, Yuanyu1 (AUTHOR), Pang, E1 (AUTHOR), Wang, Chen1 (AUTHOR), Zhao, Shaojing1 (AUTHOR), Zheng, Xiuli2 (AUTHOR), Yao, Chaoyi1 (AUTHOR), Wang, Benhua1 (AUTHOR), Song, Xiangzhi1 (AUTHOR), Yi, Jianing1,3 (AUTHOR) yijianing@hunnu.edu.cn, Lan, Minhuan1 (AUTHOR) minhuanlan@csu.edu.cn, Wang, Pengfei1,2 (AUTHOR) wangpf@mail.ipc.ac.cn
Source: Chemical Engineering Journal. Dec2025, Vol. 526, pN.PAG-N.PAG. 1p.
Subjects: Reactive oxygen species, Glutathione, Immunological adjuvants, Polythiophenes, Tumor treatment, Tumor microenvironment
Abstract: Immunosonodynamic therapy (ISDT) has unique advantages in the treatment of deep tumors. However, the low reactive oxygen species (ROS) generation efficiency of the sonosensitizer and the high concentration of glutathione (GSH) in tumor can weaken the effectiveness of sonodynamic therapy (SDT) in activating immunogenic cell death (ICD). In this work, NLG919, an ideal immune adjuvant, was covalently coupled with a long-chain alkyl group through a disulfide bond to prepare a GSH-depleted NLG919 (C16-SS-N). Next, cationic polythiophene (PT2) was assembled with C16-SS-N through hydrophobic and π-π stacking interactions. The obtained PT2-N could be disassembled by intratumoral GSH to release PT2 and NLG919, while the GSH was oxidized into negatively charged glutathione disulfide (GSSG) which can induce the conformational change of the polythiophene backbone from twist to planar through the strong electronic interaction. Such a conformational change results in increased the conjugation degree and increasing the ROS generation efficiency of PT2 under ultrasound irradiation. The GSH-depleting immune adjuvant could further enhance the efficacy of ISDT by amplifying ICD, initiating immune response, and reversing the tumor immunosuppressive microenvironment. This work provides a new strategy to improve the ROS generation efficiency of polythiophene based sonosensitizers. [Display omitted] • GSH triggers polythiophene conformational change for enhanced ROS generation. • Depleting GSH and releasing immune adjuvant to inhibit IDO-1 and reprogram immunity • Sonodynamic therapy and immune reprogramming synergistically dual amplify immune [ABSTRACT FROM AUTHOR]
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Database: Engineering Source
Description
Abstract:Immunosonodynamic therapy (ISDT) has unique advantages in the treatment of deep tumors. However, the low reactive oxygen species (ROS) generation efficiency of the sonosensitizer and the high concentration of glutathione (GSH) in tumor can weaken the effectiveness of sonodynamic therapy (SDT) in activating immunogenic cell death (ICD). In this work, NLG919, an ideal immune adjuvant, was covalently coupled with a long-chain alkyl group through a disulfide bond to prepare a GSH-depleted NLG919 (C16-SS-N). Next, cationic polythiophene (PT2) was assembled with C16-SS-N through hydrophobic and π-π stacking interactions. The obtained PT2-N could be disassembled by intratumoral GSH to release PT2 and NLG919, while the GSH was oxidized into negatively charged glutathione disulfide (GSSG) which can induce the conformational change of the polythiophene backbone from twist to planar through the strong electronic interaction. Such a conformational change results in increased the conjugation degree and increasing the ROS generation efficiency of PT2 under ultrasound irradiation. The GSH-depleting immune adjuvant could further enhance the efficacy of ISDT by amplifying ICD, initiating immune response, and reversing the tumor immunosuppressive microenvironment. This work provides a new strategy to improve the ROS generation efficiency of polythiophene based sonosensitizers. [Display omitted] • GSH triggers polythiophene conformational change for enhanced ROS generation. • Depleting GSH and releasing immune adjuvant to inhibit IDO-1 and reprogram immunity • Sonodynamic therapy and immune reprogramming synergistically dual amplify immune [ABSTRACT FROM AUTHOR]
ISSN:13858947
DOI:10.1016/j.cej.2025.171085