COMPOSITIONS AND METHOD FOR THE TREATMENT AND DETECTION OF COLON CANCER
The present invention provides methods of detecting and treating colon cancer using conjugates comprising a GCRA peptide and one or more components such as a drug delivery vehicle, a chemotherapeutic agent, a micelle, a nanoparticle, a liposome, a polymer, a lipid, an imaging agent, and a labeling agent.
1 . A conjugate comprising: (a) a GCRA peptide; and (b) one or more components, to which the GCRA peptide is conjugated, wherein the one or more components are selected from the group consisting of a drug delivery vehicle, a chemotherapeutic agent, a micelle, a nanoparticle, a liposome, a polymer, a lipid, an imaging agent, and a labeling agent.
2 . The conjugate of claim 1 , wherein the peptide and the one or more components are covalently coupled directly or via a linker.
3 . The conjugate of claim 2 , wherein the linker is 4 to 10 carbons in length.
4 . The conjugate of claim 2 , wherein the GCRA peptide maintains biological activity.
5 . The conjugate of claim 1 , wherein the drug delivery vehicle is selected from the group consisting of liposomes, polymeric micelles, lipoprotein-based drug carriers, nanoparticle drug carriers, and dendrimers.
6 . The conjugate of claim 1 , wherein the component is a drug delivery vehicle and the conjugate further comprises at least one chemotherapeutic agent encapsulated within the drug delivery vehicle.
7 . The conjugate of claim 6 , wherein the at least one chemotherapeutic agent is a taxane, an anthracyclin, a platin or 5-fluorouracil and any combination thereof.
8 . The conjugate of claim 6 , wherein the drug delivery vehicle is a nanoparticle.
9 . The conjugate of claim 8 , wherein the nanoparticle is a PLA-based or a PLGA-based nanoparticle.
10 . The conjugate of claim 1 , wherein the component is conjugated to the N-terminus of the GCRA peptide.
11 . The conjugate of claim 1 , wherein the component is an imaging agent.
12 . The conjugate of claim 1 , wherein the imaging agent is a florescence dye or radioactive moiety.
13 . The conjugate of claim 1 , wherein the component is a labeling agent.
14 . The conjugate of claim 13 , wherein the labeling agent is biotin.
15 . The conjugate of claim 14 , wherein the biotin conjugate is followed by detection with avidin or streptavidin conjugated to fluorescence dye.
16 . The conjugate of claim 1 , wherein GCRA peptide is a peptide consisting essentially of the amino acid sequence of any one of Tables 1-8.
17 . The conjugate of claim 16 , wherein GCRA peptide is SEQ ID NO: 1 (SP-304), SEQ ID NO: 8 (SP-326), SEQ ID NO.:9 (SP-333), SP364 (SEQ ID NO.:100), or SP366 (SEQ ID NO.:102).
18 . The conjugate of claim 16 , wherein the GCRA peptide does not contain a D-amino acid at the N-terminus.
19 . The conjugate of claim 16 , wherein the GCRA peptide contains a D-amino acid at the C-terminus.
20 . The conjugate of claim 16 , wherein the GCRA peptide does not contain a D-amino acid at the N-terminus and contains a D-amino acid at the C-terminus.
21 . The conjugate of claim 1 , wherein the GCRA peptide is conjugated to two components.
22 . The conjugate of claim 21 , wherein the GCRA peptide is conjugated to a nanoparticle and an imaging agent.
23 . The conjugate of claim 21 , wherein the GCRA peptide is conjugated to a nanoparticle and a chemotherapeutic.
24 . The conjugate of claims 21 - 23 , wherein the nanoparticle is conjugated to the C-terminus of the GCRA peptide.
25 . The conjugate of claim 22 , wherein the imaging agent is conjugated to the N-terminus of the GCRA peptide and the nanoparticle is conjugated to the C-terminus of the GCRA peptide.
26 . The conjugate of claim 23 , wherein the chemotherapeutic agent is conjugated to the N-terminus of the GCRA peptide and the nanoparticle is conjugated to the C-terminus of the GCRA peptide.
27 . A composition comprising the conjugate of any one of the preceding claims and a pharmaceutically acceptable excipient.
28 . A method for the reduction of the incidence of colonic adenomas and colonic microadenomas in subject comprising administering to the subject a composition of claim 27 , wherein the component is chemotherapeutic agent or a drug delivery vehicle, a micelle, a nanoparticle, a liposome, a polymer, a lipid having at least one chemotherapeutic agent encapsulated within.
29 . A method for reducing the incidence of colon cancer in subject comprising administering to the subject a composition of claim 27 , wherein the component is chemotherapeutic agent or a drug delivery vehicle, a micelle, a nanoparticle, a liposome, a polymer, a lipid having at least one chemotherapeutic agent encapsulated within.
30 . A method for reducing the incidence of colon cancer metastasis in subject comprising administering to the subject a composition of claim 27 , wherein the component is chemotherapeutic agent or a drug delivery vehicle, a micelle, a nanoparticle, a liposome, a polymer, a lipid having at least one chemotherapeutic agent encapsulated within.
31 . A method of lowering the risk of adenoma development in subject comprising administering to the subject a composition of claim 27 , wherein the component is chemotherapeutic agent or a drug delivery vehicle, a micelle, a nanoparticle, a liposome, a polymer, a lipid having at least one chemotherapeutic agent encapsulated within.
32 . A method of treating colon cancer metastases in subject comprising administering to the subject a composition of claim 27 , wherein the component is chemotherapeutic agent or a drug delivery vehicle, a micelle, a nanoparticle, a liposome, a polymer, a lipid having at least one chemotherapeutic agent encapsulated within.
33 . The method of any one of claims 29 - 32 , wherein the subject is at risk of developing such adenomas or microadenomas.
34 . The method of claim 33 , wherein the subject has been diagnosed with colon cancer, colonic adenomas, colonic microadenomas or colonic polyps or has a close blood relative diagnosed with colon cancer, colonic adenomas, colonic microadenomas or colonic polyps.
35 . A method of detecting a colonic microadenoma or a flat colorectal dysplasias comprising contacting colonic tissue with a composition of claim 27 , wherein the component is an imaging agent or labeling agent.
36 . A method of detecting colorectal cancer metastasis or a flat colorectal dysplasias by administering to the subject a composition of claim 27 , wherein the component is an imaging agent and detecting said imaging agent in the subject.