Tumor-Activated Prodrug with Synergistic Anti-Stemness Chemical and Photodynamic Therapies

Jianhua Xiong, Xiaoyu Wang, Jaewon Kim, Jiankang Gong, Zhiqiang Mao, Jong Seung Kim, Zhihong Liu

Research output: Contribution to journalArticlepeer-review


Photodynamic therapy (PDT) has received extensive attention as a promising cancer treatment approach. Still, challenges to in vivo photodynamic therapy have existed for decades. First, the “always on” nature of conventional photosensitizers will cause damage to normal tissues thereby limiting the treatment efficiency of PDT. Second, the hypoxic TME protects cancer stem cells (CSCs) deeply harbored in the center of tumors from PDT administration, thus contributing to the recrudescence and metastasis of tumors. Herein, a ROS-triggered self-immolative therapeutic prodrug (Mu-PS) is reported, comprising of an activatable photosensitizer, an indomethacin (IMC) part, and a ROS-responsive trigger, for the anti-stemness chemical and photodynamic therapy of tumors. Intriguingly, Mu-PS can target the tumor and selectively release the photosensitizer and IMC upon the activation of TME-related ROS, generating massive phototoxic 1O2 to kill most non-CSCs tumor cells under the action of PDT and block the growth of CSCs by IMC, hence, it multiplies the therapeutic index. Noteworthy, the anti-stemness mechanism of IMC in tumors is confirmed and elucidated for the first time. Overall, this study introduces a self-immolatative prodrug for combined CSCs-involved chemical therapy and activatable PDT for tumors and provides a design paradigm of prodrug for the precise prognosis and treatment of tumors.

Original languageEnglish
Article number2312590
JournalAdvanced Functional Materials
Issue number10
Publication statusPublished - 2024 Mar 4

Bibliographical note

Publisher Copyright:
© 2023 Wiley-VCH GmbH.


  • cancer stem cells (CSCs)
  • cancer therapy
  • chemotherapy
  • photodynamic therapy
  • prodrug

ASJC Scopus subject areas

  • Electronic, Optical and Magnetic Materials
  • General Chemistry
  • Biomaterials
  • General Materials Science
  • Condensed Matter Physics
  • Electrochemistry


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