Cyclodextrin-based rotaxanes as a versatile platform for biological and medicinal applications

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Mechanically interlocked molecules (MIMs) such as rotaxanes and catenanes attract significant interest due to their unique structures and dynamic properties. Cyclodextrin-based rotaxanes (CD-rotaxanes) have emerged as promising supramolecular systems for biological and medicinal applications. Their host-guest interactions and mechanical bonds provide enhanced stability, stimuli-responsiveness, and tunable functionality. This review highlights their diverse uses, including drug targeting and delivery, medical imaging, controlled drug release, enzyme inhibition, biomolecule transport, and as theranostic agents. 

An interesting example is methylated-β-CDs threaded onacid-labile polymer resulting in a polyrotaxane which releases methylated-β-CDs in acidic conditions like lysosomes to interact with organelle membranes and trigger autophagy.

Illustration depicting the acid-triggered disassembly of methylated-β-cyclodextrin (Me-β-CD) within endosomes, showing its release at different pH levels and interaction with organelle membranes.

Fig. 2: Acid-triggered disassembly of Me-β-CD.

Paryente, S., Aledwan, H. & Saady, A. Cyclodextrin-based rotaxanes as a versatile platform for biological and medicinal applications. Commun Chem 8, 149 (2025). https://doi.org/10.1038/s42004-025-01555-6

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