Lung protease nanosensors and uses thereof
AssigneeMassachusetts Institute of Technology
InventorsSangeeta N. Bhatia, Jesse Kirkpatrick, Jaideep S. Dudani, Colin Buss, Andrew David Warren
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Abstract
Aspects of the present disclosure relate to methods and compositions useful for in vivo and/or in vitro profiling of proteases present in the lung. In some embodiments, the disclosure provides methods of in vivo enzymatic processing of exogenous molecules followed by detection of detectable markers as representative of the presence of active proteases associated with a lung disease, for example, lung cancer and lung infections. In some embodiments, the disclosure provides compositions and methods for production of a lung disease signature and diagnosis of lung disease.
Claims20
A method comprising
- detecting a detectable marker in a blood sample or urine sample obtained from a subject that has been administered to the lung of the subject by inhalation or intratracheal administration a lung protease nanosensor comprising:
- (a) (i) a multi-arm polyethylene glycol molecule (multi-arm PEG) scaffold and/or (ii) a polyethylene glycol (PEG) scaffold with a molecular weight equal to or greater than 40 kDa;
- linked to
- (b) a substrate,
- wherein the substrate is conjugated to a detectable marker,
- wherein the detectable marker is released from the nanosensor when exposed to a protease present in a lung, and
- wherein the subject has or is suspected of having lung cancer.
The method of 1, wherein the lung protease nanosensor is delivered to the lung using an aerosol delivery device which is not reliant on propellant or compressed air.
A method for classifying lung disease in a subject, the method comprising:
- (i) detecting in a biological sample obtained from a subject that has been administered one or more lung protease nanosensors, wherein the one or more lung protease nanosensors have been administered to the lung of the subject by inhalation or intratracheal administration:
- one or more detectable markers that have been released from the one or more lung protease nanosensors when exposed to an enzyme present in the lung of the subject, wherein each of the one or more lung protease nanosensors comprises:
- (a) (1) a multi-arm polyethylene glycol molecule (multi-arm PEG) scaffold and/or (2) a polyethylene glycol (PEG) scaffold with a molecular weight equal to or greater than 40 kDa;
- linked to
- (b) a substrate,
- wherein the substrate is conjugated to a detectable marker,
- wherein the detectable marker is released from the nanosensor when exposed to a protease present in a lung, and
- wherein the biological sample is a blood sample or urine sample;
- and
- (ii) classifying the subject as having a type of lung disease based on the identity of the detectable markers present in the biological sample, wherein the presence of the detectable markers in the biological sample is indicative of one or more cancer-associated enzymes being present in an active form within the lung of the subject.
A method comprising:
- (a) administering to the lung of a subject, by inhalation or intratracheal administration, a lung protease nanosensor comprising:
- (i) (1) a multi-arm polyethylene glycol molecule (multi-arm PEG) scaffold and/or (2) a polyethylene glycol (PEG) scaffold with a molecular weight equal to or greater than 40 kDa;
- linked to
- (ii) a lung infection substrate,
- wherein the substrate is conjugated to a detectable marker,
- wherein the substrate includes a detectable marker,
- whereby the detectable marker is released from the lung protease nanosensor when exposed to a protease present in the lung, and
- wherein the subject has or is suspected of having a lung infection;
- and
- (b) detecting and quantifying the detectable marker from a blood sample or a urine sample from the subject.
Dependencies are inferred from the claim text.