ArticleJournal of enzyme inhibition and medicinal chemistry2022
Inhibitory prodrug mechanism for cysteine cathepsin-targeted self-controlled drug release.
Article in Journal of enzyme inhibition and medicinal chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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3 citing papers in PubMed.
- Macrophage reprogramming through scavenger receptor-guided and cathepsin B-triggered nanodelivery: from intracellular mechanisms to translational applications.Frontiers in immunology · 2026Review
- Peptidomimetic Phenoxymethyl Ketone Warheads as Potent Dual-Mode Inhibitors against SARS-CoV-2 MJournal of medicinal chemistry · 2025Article
- Ruthenium-Cathepsin Inhibitor Conjugates for Green Light-Activated Photodynamic Therapy and Photochemotherapy.Inorganic chemistry · 2024Article
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2 authors.
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Abstract
Tumour-associated macrophages (TAMs) support tumour development and have emerged as important regulators of therapeutic response to cytostatic agents. To target TAMs, we have developed a novel drug delivery approach which induces drug release as it inhibits cysteine cathepsin activity. This inhibitory prodrug (IPD) approach establishes a self-regulated system where drug release stops after all cysteine cathepsins are inhibited. This could improve the therapeutic window for drugs with severe side effects. We demonstrate and characterise this self-regulation concept with a fluorogenic IPD model. Next, we applied this IPD strategy to deliver cytotoxic drugs, as doxorubicin and monomethyl auristatin E, which are efficiently released and dose-dependently eliminate RAW264.7 macrophages. Lastly, by exploiting the increased cathepsin activity in TAM-like M2-polarised primary macrophages, we show that IPD-Dox selectively eliminates M2 over M1 macrophages. This demonstrates the potential of our IPD strategy for selective drug delivery and modulation of the tumour microenvironment.
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