Targeting damaged lung tissue
The present invention relates to methods and compositions for targeting damaged lung tissue. Compositions provided feature a targeting moiety coupled to one or more other moieties, including, for example, a cross-linkable moiety, an imaging moiety, and/or one or more other targeting moieties. The methods and compositions of the invention find use, for example, in detecting and treating a pulmonary condition such as emphysema.
1 . A method of reducing lung volume comprising:
administering to a subject a composition comprising a cross-linkable moiety and a targeting moiety wherein said moieties are coupled and wherein said targeting moiety targets damaged lung tissue; and
cross-linking said damaged lung tissue, thereby reducing lung volume.
2 . The method as recited in claim 1 wherein said lung tissue comprises epithelial lining fluid.
3 . The method as recited in claim 1 wherein said method is performed without prior identification of said damaged lung tissue.
4 . The method as recited in claim 1 wherein said method does not damage epithelial cells within lung tissue.
5 . The method as recited in claim 1 wherein said method damages epithelial cells within lung tissue by use of a sclerosing agent.
6 . The method as recited in claim 5 wherein said sclerosing agent is at least one compound selected from doxycycline, bleomycin, minocycline, doxorubicin, cisplatin+cytarabine, mitoxantrone, Corynebacterium Parvum , streptokinase, and urokinase.
7 . The method as recited in claim 1 wherein said composition does not comprise a polysaccharide or a carbohydrate moiety.
8 . The method as recited in claim 1 wherein said composition does not comprise a mutant plasminogen activator-inhibitor type 1.
9 . The method as recited in claim 1 wherein said targeting moiety targets a damage-correlated moiety.
10 . The method as recited in claim 9 wherein said damage-correlated moiety comprises a cell surface marker.
11 . The method as recited in claim 9 wherein said damage-correlated moiety comprises an ECM component.
12 . The method as recited in claim 1 wherein said targeting moiety targets elastase.
13 . The method as recited in claim 1 wherein said targeting moiety targets neutrophil elastase.
14 . The method as recited in claim 1 wherein said targeting moiety comprises a protease inhibitor moiety.
15 . The method as recited in claim 1 wherein said targeting moiety comprises an alpha-1 antitrypsin moiety.
16 . The method as recited in claim 15 wherein said alpha-1 antitrypsin moiety is a recombinant alpha-1 antitrypsin moiety.
17 . The method as recited in claim 1 wherein said targeting moiety comprises an elafin moiety.
18 . The method as recited in claim 17 wherein said elafin moiety is a recombinant elafin moiety.
19 . The method as recited in claim 1 wherein said targeting moiety comprises a serpin moiety.
20 . The method as recited in claim 19 wherein said serpin moiety is a recombinant serpin moiety.
21 . The method as recited in claim 19 wherein said serpin moiety is a secretory leukoprotease inhibitor (SLP1) moiety.
22 . The method as recited in claim 21 wherein said secretory leukoprotease inhibitor (SLP1) moiety is a recombinant secretory leukoprotease inhibitor (SLP1) moiety.
23 . The method as recited in claim 1 wherein said targeting moiety targets at least one matrix metalloproteinase selected from MMP-1, MMP-2, MMP-3, MMP-4, MMP-5, MMP-6, MMP-7, MMP-8, and MMP-9.
24 . The method as recited in claim 23 wherein said composition does not comprise a hyaluronic acid or a salt thereof.
25 . The method as recited in claim 1 wherein said targeting moiety targets desmosine and/or isodesmosine.
26 . The method as recited in claim 1 wherein said targeting moiety targets CD8 and/or CD4.
27 . The method as recited in claim 1 wherein said targeting moiety targets a smoke-related moiety.
28 . The method as recited in claim 1 wherein said cross-linkable moiety comprises a hydroxyl group.
29 . The method as recited in claim 1 wherein said cross-linkable moiety comprises a carboxyl group.
30 . The method as recited in claim 1 wherein said cross-linkable moiety comprises an ester group.
31 . The method as recited in claim 1 wherein said cross-linkable moiety comprises a cyano group.
32 . The method as recited in claim 1 wherein said cross-linkable moiety comprises a thiol group.
33 . The method as recited in claim 1 wherein said cross-linkable moiety comprises a cysteine group.
34 . The method as recited in claim 1 wherein said cross-linkable moiety comprises a carbonyl group.
35 . The method as recited in claim 1 wherein said cross-linkable moiety comprises an aldehyde group.
36 . The method as recited in claim 1 wherein said cross-linkable moiety comprises a ketone group.
37 . The method as recited in claim 1 wherein said cross-linkable moiety comprises a primary amine group and/or a secondary amine group.
38 . The method as recited in claim 1 wherein said cross-linkable moiety comprises a lysine group.
39 . The method as recited in claim 1 wherein said cross-linkable moiety comprises a fibrinogen and/or a fibrin.
40 . The method as recited in claim 1 wherein said composition is less than 10 microns.
41 . The method as recited in claim 1 wherein said composition is less than 5 microns.
42 . The method as recited in claim 1 wherein said composition is less than 1 micron.
43 . The method as recited in claim 1 wherein said administering is carried out via inhalation.
44 . The method as recited in claim 43 wherein said inhalation is carried out via the mouth.
45 . The method as recited in claim 1 wherein said administering is carried out via trans-thoracic administration.
46 . The method as recited in claim 1 , further comprising administering a second composition comprising a cross-linking activating moiety.
47 . The method as recited in claim 46 wherein said cross-linking activating moiety comprises at least one group selected from a diol, a polyol, a dicarboxylic acid, a polycarboxylic acid, a diester, a polyester, a diamine, and a polyamine.
48 . The method as recited in claim 46 wherein said cross-linking activating moiety comprises at least one group selected from an alkyl bis(2-cyanoacrylate), a triallyl isocyanurate, an alkylene diacrylate, an alkylene dimethacrylate, and a trimethylol propane triacrylate.
49 . The method as recited in claim 46 wherein said cross-linking activating moiety comprises at least one group selected from a disulfide, a carbodiimide, and a hydrazine.
50 . The method as recited in claim 46 wherein said cross-linking activating moiety comprises a fibrin activator and/or a fibrinogen activator.
51 . The method as recited in claim 1 , further comprising administering a growth factor.
52 . The method as recited in claim 1 , further comprising administering an anti-surfactant.
53 . The method as recited in claim 1 , further comprising administering an antibiotic.
54 . The method as recited in claim 1 , further comprising collapsing a first portion or all of the lung of said subject.
55 . The method as recited in claim 54 wherein said collapsing comprises use of negative pressure from within the lung of said subject.
56 . The method as recited in claim 54 wherein said collapsing comprises use of positive pressure from without the lung of said subject.
57 . The method as recited in claim 54 , further comprising re-inflating a second portion of the lung of said subject wherein said second portion does not comprise said damaged lung tissue.
58 . The method as recited in claim 1 wherein said composition further comprises an imaging moiety coupled to said targeting moiety and/or said cross-linkable moiety.
59 . The method as recited in claim 58 , further comprising imaging said damaged lung tissue.
60 . The method as recited in claim 1 , further comprising administering a washing moiety.
61 . A method of treating a pulmonary condition comprising:
administering to a subject a composition comprising a cross-linkable moiety and a targeting moiety wherein said moieties are coupled and wherein said targeting moiety targets damaged lung tissue; and
cross-linking said damaged lung tissue, thereby treating said pulmonary condition.
62 . The method as recited in claim 61 wherein said lung tissue comprises epithelial lining fluid.
63 . The method as recited in claim 61 wherein said pulmonary condition is emphysema.
64 . The method as recited in claim 61 wherein said pulmonary condition is COPD.