USE OF PYRENE TO CARRY NON-PEPTIDE AGENTS ACROSS THE BLOOD BRAIN BARRIER
Described are methods for delivering a non-peptide agent across the blood-brain barrier, comprising administering to a subject a conjugate comprising (i) a non-peptide agent and (ii) pyrene, and related detection and therapeutic method.
1 . A method for delivering a non-peptide agent across the blood-brain barrier, comprising administering to a subject a conjugate comprising:
(i) a non-peptide agent; and
(ii) pyrene.
2 . The method of claim 1 , wherein the non-peptide agent is a detection agent or a therapeutic agent.
3 . The method of claim 1 , wherein the non-peptide agent is a detection agent capable of identifying a protein or structure associated with a neurological condition.
4 . The method of claim 1 , wherein the non-peptide agent is a therapeutic agent useful in treating a neurological condition.
5 . The method of claim 1 , wherein the non-peptide agent is a polynucleotide detection or therapeutic agent.
6 . The method of claim 1 , wherein the non-peptide agent is a small molecule therapeutic agent.
7 . The method of claim 1 , wherein the conjugate further comprises a detectable label.
8 . The method of claim 1 , wherein the pyrene is a pyrene derivative.
9 . The method of claim 1 , wherein the pyrene derivative is selected from alkyl pyrene, amino pyrene, pyrene carboxylate, pyrene butyrate, albumin-pyrene, PEGylated pyrene, a pyrene derivative comprising a free carboxyl group and a pyrene derivative comprising a free amine group.
10 . The method of claim 1 , wherein conjugate exhibits enhanced permeability across the blood brain barrier as compared to the non-peptide agent.
11 . An in vivo detection method comprising
(a) administering to a subject a conjugate comprising (i) a non-peptide detection agent and (ii) pyrene and
(b) detecting non-peptide detection agent that has localized in the brain of the subject.
12 . The method of claim 11 , wherein step (b) comprises detecting pyrene fluorescence.
13 . The method of claim 11 , wherein the detection agent is capable of identifying a protein or structure associated with a neurological condition.
14 . The method of claim 11 , wherein the detection agent selectively binds to an amyloid protein or structure associated with a neurological condition.
15 . The method of claim 11 , wherein the conjugate further comprises a detectable label.
16 . The method of claim 15 , wherein the label is selected from the group consisting of fluorophores, MRI contrast agents, ion emitters, and radioactive labels.
17 . A method of treating a neurological disorder, comprising administering to a subject a conjugate comprising (i) a non-peptide therapeutic agent and (ii) pyrene.
18 . The method of claim 17 , wherein the non-peptide agent is a therapeutic agent useful in treating a neurological condition.
19 . The method of claim 17 , wherein the non-peptide agent is an anti-amyloid agent.
20 . The method of claim 17 , wherein the method comprises administering a therapeutically effective amount of the conjugate.