Rotaxane-type probe for molecular imaging
The invention provides a novel method for synthesizing hyperpolarized xenon-129 (HP Xe) biosensors by using pseudo-rotaxane structures of gamma-cyclodextrin. These supramolecular complexes form novel ternary structures in the presence of HP Xe which can be detected via 129 Xe MR spectroscopy and imaging techniques. The rotaxane-type complex can be tagged with an affinity label for detecting a target in a biological subject.
1. A supramolecular complex useful as a biosensor, comprising:
(a) a macrocycle host defining a hydrophobic cavity;
(b) an axle comprising a molecular chain functionalized with an affinity tag for a target inside a biological subject, wherein the affinity tag is at one or both ends of the molecular chain, and wherein the axle is threaded through the macrocycle cavity; and
(c) a xenon atom, wherein the cavity of the macrocycle host is large enough to accommodate and reversibly encapsulate both a cross section of the axle and the xenon atom at the same time.
2. The supramolecular complex of claim 1 , wherein the macrocycle host is water-soluble.
3. The supramolecular complex of claim 1 , wherein the xenon atom is dissolved in a solution.
4. The supramolecular complex of claim 1 , wherein the macrocycle host defines a cavity that is larger than about 6.5 Å in inner diameter.
5. The supramolecular complex of claim 1 , wherein the macrocycle host is a cyclodextrin.
6. The supramolecular complex of claim 5 , wherein the macrocycle host is a γ-cyclodextrin.
7. The supramolecular complex of claim 1 , wherein the axle comprises an alkyl chain.
8. The supramolecular complex of claim 7 , wherein the axle has at least five carbons in its backbone.
9. The supramolecular complex of claim 1 , wherein the axle is capped with a hydrophobic end group at each of its two ends, at least one of the end groups being or comprising the affinity tag.
10. The supramolecular complex of claim 1 , wherein the affinity tag comprises a ligand selected for its affinity for a biological target inside a subject.
11. The supramolecular complex of claim 1 , wherein the affinity tag comprises a detectable label.
12. The supramolecular complex of claim 11 , wherein the affinity tag comprises a fluorophore.
13. The supramolecular complex of claim 1 , wherein the affinity tag comprises thioflavin T.
14. The supramolecular complex of claim 1 , detectable by xenon-based magnetic resonance imaging or spectroscopy.
15. A biosensor comprising:
(a) a cyclodextrin molecule defining a cavity;
(b) an alkyl chain molecule functionalized with an affinity tag at one or each of its two ends, wherein the affinity tag has an affinity for a target inside a biological subject, and wherein the alkyl chain molecule is threaded through the cavity in the cyclodextrin; and
(c) a xenon atom in the cavity of the cyclodextrin.
16. The biosensor of claim 15 , wherein the affinity tag comprises a detectable label.
17. The biosensor of claim 15 , wherein the affinity tag is part of an end group that also serves as a stopper to prevent de-threading.
18. The biosensor of claim 17 , wherein the end group is hydrophobic.
19. The biosensor of claim 17 , wherein the end group comprises an ethylimidazolium group or an anthracene group.
20. The biosensor of claim 15 , wherein the xenon atom is xenon-129.