Photodynamic quenched cathepsin activity based probes for cancer detection and macrophage targeted therapy

Yael Ben-Nun, Emmanuelle Merquiol, Alexander Brandis, Boris Turk, Avigdor Scherz, Galia Blum*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Elevated cathepsins levels and activities are found in several types of human cancer, making them valuable biomarkers for detection and targeting therapeutics. We designed small molecule quenched activity-based probes (qABPs) that fluoresce upon activity-dependent covalent modification, yielding cell killing by Photodynamic Therapy (PDT). These novel molecules are highly selective theranostic probes that enable both detection and treatment of cancer with minimal side effects. Our qABPs carry a photosensitizer (PS), which is activated by light, resulting in oxidative stress and subsequent cell ablation, and a quencher that when removed by active cathepsins allow the PS to fluoresce and demonstrate PD properties. Our most powerful and stable PS-qABP, YBN14, consists of a selective cathepsin recognition sequence, a QC-1 quencher and a new bacteriochlorin derivative as a PS. YBN14 allowed rapid and selective non-invasive in vivo imaging of subcutaneous tumors and induced specific tumor macrophage apoptosis by light treatment, resulting in a substantial tumor shrinkage in an aggressive breast cancer mouse model. These results demonstrate for the first time that the PS-qABPs technology offers a functional theranostic tool, which can be applied to numerous tumor types and other inflammation-associated diseases.

Original languageAmerican English
Pages (from-to)847-862
Number of pages16
Issue number8
StatePublished - 2015

Bibliographical note

Publisher Copyright:
© 2015 Ivyspring International Publisher.


  • Activity-based probes
  • Cathepsins
  • Macrophages
  • Non-invasive imaging
  • Photodynamic therapy


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