Supramolecular Rotaxane‐Based Multi‐Modal Probes for Cancer Biomarker Imaging**

Abstract

Mechanically interlocked molecules present opportunities to construct therapeutic drugs and diagnostic imaging agents but harnessing supramolecular chemistry to make biologically active probes in water is a challenge. Here, we describe a rotaxane-based approach to synthesise radiolabelled proteins and peptides for molecular imaging of cancer biomarkers in vivo. Host-guest chemistry using β-cyclodextrin-and cucurbit-[6]uril-catalysed cooperative capture synthesis produced gallium-68 or zirconium-89 radiolabelled metallo-[4]rotaxanes. Photochemical conjugation to trastuzumab led to a viable positron emission tomography (PET) radiotracer. The rotaxane architecture can be tuned to accommodate different radiometal ion complexes, other protein-or peptide-based drugs, and fluorophores for optical detection. This technology provides a platform to explore how mechanical bonding can improve drug delivery, enhance tumour specificity, control radiotracer pharmacokinetics, and reduce dosimetry.

A supramolecular cucurbit[8]uril-based rotaxane chemosensor for the optical tryptophan detection in human serum and urine

“…Many fascinating supramolecular studies of cucurbit[n]uril-based rotaxanes and pseudorotaxanes have appeared since the early days of CBn (re)discovery [58][59][60][61] . In 2011, the first CB8-based rotaxane that can complex additional aromatic guests in aqueous and organic media was presented 28 .…”

para–Phenylenediamine Dimer as a Redox–Active Guest for Supramolecular Systems

“…[32][33][34][35] While these structures are of particular interest in material sciences due to their polymeric nature, [36][37][38] recent advancements have introduced guest molecules featuring multiple specific binding motifs with varying selectivity towards macrocyclic compounds. This innovation enables the construction of functionalised supramolecular structures such as molecular machines, [39] room-temperature phosphorescence switches, [40,41] probes [42] and rotaxane catalysts. [43] Notably, significant attention has been directed towards supramolecular systems responsive to external stimuli such as light, pH, temperature, and redox processes.…”

Cyclodextrin-Catalyzed Diels–Alder Reaction for the Syntheses of Cyclodextrin Polyrotaxanes, Molecular Tubes, and Molecular Shuttles

“…Cyclodextrin (CD) polyrotaxanes (PRs) are a type of stable, facilely modifiable, and environment-friendly supramolecular architectures. − CD rings can freely slide and rotate on the polymer axle, endowing CD PRs with intriguing functions. − For example, when used as cross-linking agents of elastomers, CD PRs can significantly improve their extensibility due to the movement of the CD rings on the axle. − In another case, CD PRs exhibit enhanced interactions with cell surfaces because the mobility of the CD rings enables PRs to fit the interaction interfaces. − Furthermore, when the end-capping groups of PRs are cleavable, CD tubes can be prepared by cross-linking the adjacent CD rings in PRs, cleaving the end-capping groups and removing the polymer axles. , CD tubes are biocompatible hosts for various small molecules. , When the number of CD rings in a PR decreases to a certain value, a rotaxane is formed. The achievement of controlled and cyclic motion of the CD ring in rotaxanes can make them function as molecular machines. − …”