Inhalable nanosensors with volatile reporters and uses thereof
In some aspects, the disclosure relates to compositions and method for detection, classification, and treatment of disease or other body status. The methods and compositions may be methods or compositions for identification of pathogenic infections or other diseases in patients using an inhalable nanosensor having a volatile reporter. The disclosure is based, in part, on synthetic biomarkers (e.g., inhalable nanosensors) that are capable of distinguishing (e.g., classifying) different disease or status associated enzymes in a subject by examining the effect of those enzymes on a synthetic volatile reporter.
1. A nanosensor comprising a scaffold linked to a synthetic volatile reporter via an enzymatic substrate, wherein the volatile reporter is capable of being released from the nanosensor when exposed to an enzyme present in a lung of a subject.
2. The nanosensor of claim 1 , wherein the scaffold comprises a biological macromolecule, a synthetic macromolecule, or a particle.
3. The nanosensor of claim 2 , wherein the biological macromolecule is a protein, lipid, carbohydrate, or a nucleic acid.
4. The nanosensor of claim 2 , wherein the synthetic macromolecule is a synthetic polymer.
5. The nanosensor of claim 2 , wherein the particle is a nanoparticle or a microparticle.
6. The nanosensor of claim 2 , wherein the scaffold has total molecular weight greater than 40 kDa.
7. The nanosensor of claim 2 , wherein the synthetic volatile reporter comprises at least one perfluorocarbon.
8. The nanosensor of claim 7 , wherein the perfluorocarbon has the chemical formula CF 3 (CF 2 ) x CH 2 NH 2 , wherein x is a number in a range of 1 to 100.
9. The nanosensor of claim 1 , wherein the scaffold comprises a multi-arm polyethylene glycol molecule (multi-arm PEG).
10. The nanosensor of claim 9 , wherein the multi-arm PEG has a total molecular weight greater than 40 kDa.
11. The nanosensor of claim 1 or 2 , wherein the scaffold is linked to a single enzymatic substrate.
12. The nanosensor of claim 1 , wherein the enzymatic substrate comprises an infectious agent substrate.
13. A method comprising:
(a) detecting in a breath sample obtained from a subject that has been administered one or more nanosensors of claim 12 one or more volatile reporters that have been released from the one or more nanosensors when exposed to the enzyme present in the lung of the subject; and
(b) classifying the subject as having an infection upon detection of the one or more volatile reporters.
14. The nanosensor of claim 12 , wherein the enzymatic substrate is cleaved by an enzyme associated with an infection in a subject.
15. The nanosensor of claim 1 , wherein the scaffold is linked to a single volatile reporter.
16. The nanosensor of claim 1 , wherein the scaffold is linked to multiple volatile reporters via one or more enzymatic substrates.
17. The nanosensor of claim 1 , wherein the scaffold is linked to 2 to 20 different enzymatic substrates.
18. The nanosensor of claim 1 , wherein the enzymatic substrate is a peptide, a nucleic acid, a glycan, or a lipid.
19. The nanosensor of claim 1 , wherein the synthetic volatile reporter comprises at least one perfluorocarbon.
20. The nanosensor of claim 19 , wherein the perfluorocarbon has the chemical formula CF 3 (CF 2 ) x CH 2 NH 2 , wherein x is a number in a range of 1 to 100.
21. The nanosensor of claim 20 , wherein the perfluorocarbon is pentafluoropropylamine or heptafluorobutylamine.
22. A method comprising detecting in a breath sample obtained from a subject that has been administered one or more nanosensors of claim 1 one or more volatile reporters that have been released from the one or more nanosensors when exposed to the enzyme present in the lung of the subject.
23. The method of claim 22 , wherein the detecting comprises mass spectrometry, ion mobility spectroscopy, or any combination thereof.
24. The method of claim 22 , wherein the administration of the one or more nanosensors is by inhalation.
25. A method comprising:
(a) administering one or more nanosensors of claim 1 to a subject; and
(b) detecting in a breath sample obtained from the subject one or more volatile reporters that have been released from the one or more nanosensors when exposed to the enzyme present in the lung of the subject.
26. The method of claim 25 , wherein the subject has, is suspected of having, or is at risk for an infectious disease.
27. The method of claim 26 , wherein the subject has, is suspected of having, or is at risk for pneumonia.
28. The method of claim 25 , wherein an increase in the presence of the one or more volatile reporters relative to a level of the one or more volatile reporters from a healthy subject is indicative of the subject having a disease.