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Programmed sequential nanostructural conversion at nano-bio interface for synergistic cancer phototheranostics

Acta Pharmacologica Sinica volume 46, pages 3343–3354 (2025)Cite this article

Abstract

Prodrugs usually convert into active compounds within cells via endogenous or external stimuli to improve the diagnostic accuracy and therapeutic efficacy, but this singular release profile often fails to meet the multifunctional needs of cancer therapeutics. In this study we proposed a strategy of “nanostructural conversion at nano-bio interface” and constructed a small-molecule nanoprodrug (APO-S-Cy7-TCF) for multifunctional anti-tumor phototheranostics. Upon exposure to redox biomolecules (ROS/GSH) in tumor microenvironment, the pristine nanostructure of APO-S-Cy7-TCF disassembled, releasing Cy7-TCF-OH and APO that interacted with heat shock proteins to initiate apoptosis. Cy7-TCF-OH could then re-assemble into smaller nanosaucers with enhanced photothermal properties and self-augmented ROS-generating capacity, enabling synergistic phototherapy for tumor ablation. In particular, Cy7-TCF-OH nanosaucers were long retained in residual tumors and could further interact with albumin to form smaller Cy7-TCF-OH@albumin nanocomposites that time-dependently activated near-infrared fluorescence for prognostic assessment. Using these biomolecule-derived elements to program supramolecular sequential structural conversions at nano-bio interface, our study establishes a new way for small-molecule-based multifunctional phototheranostic platform.

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Fig. 1
Fig. 2: Self-assembly of APO-S-Cy7-TCF in aqueous solution.
Fig. 3: The structural conversion of APO-S-Cy7-TCF SM-NPs.
Fig. 4: Photothermal therapeutic performance of APO-S-Cy7-TCF SM-NPs in cells.
Fig. 5: Fluorescence imaging and metabolism of APO-S-Cy7-TCF SM-NPs in vivo, using APO/Cy7-TCF-OH in Pluronic F127 as controls.
Fig. 6: APO-S-Cy7-TCF SM-NPs-mediated low-temperature PTT in vivo.
Fig. 7: Biosafety of APO-S-Cy7-TCF SM-NPs-mediated low-temperature PTT in vivo.

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Acknowledgements

Financial support was provided by National Natural Science Foundation of China (22071128), Shandong Provincial Natural Science Foundation (ZR2020ZD31, ZR2023QB077), and Qingdao Postdoctoral Foundation (QDBSH20230102053).

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Author notes

  1. These authors contributed equally: Shi Sun, Rui Wang.

Authors and Affiliations

  1. College of Material Science and Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China

    Shi Sun, Rui Wang, Xue-lu-er Mu, Wen-bi Feng, Hao Kong, Ya-jie Li, Min Gao & Xian-feng Zhou

  2. College of Polymer Science and Engineering, Qingdao University of Science and Technology, Qingdao, 266042, China

    Ying-xi Lu & Xian-feng Zhou

  3. Department of Anesthesiology, Qingdao Traditional Chinese Medicine Hospital, Qingdao Hiser Hospital Affiliated of Qingdao University, Qingdao, 266000, China

    Hui-rui Sun

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Contributions

XFZ, SS, and RW conceived and designed the study. SS, RW, and XLEM acquired and analyzed data. WBF and HK collected and analyzed cellular and animal data. YJL and MG interpreted the data. SS, RW and XFZ wrote the paper. HRS interpreted the data and supervised the project. YXL and XFZ acquired funding and supervised the project.

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Correspondence to Ying-xi Lu, Hui-rui Sun or Xian-feng Zhou.

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Sun, S., Wang, R., Mu, Xle. et al. Programmed sequential nanostructural conversion at nano-bio interface for synergistic cancer phototheranostics. Acta Pharmacol Sin 46, 3343–3354 (2025). https://doi.org/10.1038/s41401-025-01609-4

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