Peptide having cancer selective translocation function and use thereof

Abstract

The present invention relates a peptide having cancer selective translocation function, and the use thereof, and more particularly to a VEGF-binding protein transduction domain (VPTD) represented as SEQ ID NO: 1 or a heparin-binding protein transduction domain (HPTD) represented as SEQ ID NO: 2, which bind specifically to VEGF and heparin, which are overexpressed specifically in tumor cells or tumor tissues, and to a conjugate comprising a drug linked to the peptide. The peptide and the peptide-drug conjugate bind specifically to VEGF and heparin in tumor cells or tumor tissue and accumulate in the tumor cells or tumor tissue, and thus can be used for the accurate diagnosis and treatment of cancer. Also, the non-specific distribution of the peptide or the conjugate in the body after administration is inhibited, and thus the side effects thereof can be minimized. Accordingly, the peptide or the conjugate is useful for the diagnosis and treatment of cancer.

1 . A peptide having cancer selective translocation function comprising VPTD (VEGF-binding protein transduction domain peptide) peptide represented as SEQ ID NO: 1 or HPTD (heparin-binding protein transduction domain) peptide represented as SEQ ID NO: 2. 
     
     
         2 . The peptide having cancer selective translocation function of  claim 1 , wherein the VPTD peptide represented as SEQ ID NO: 1 or the HPTD peptide represented as SEQ ID NO: 2 binds specifically to vascular endothelial growth factor (VEGF) and heparin in tumor cells or tumor tissues. 
     
     
         3 . The peptide having cancer selective translocation function of  claim 1 , wherein the VPTD peptide represented as SEQ ID NO: 1 or the HPTD peptide represented as SEQ ID NO: 2 is composed of D-type or L-type amino acids and contains one or more amino acids selected from the group consisting of arginine, lysine and histidine in an amount of 70-80%. 
     
     
         4 . The peptide having cancer selective translocation function of  claim 1 , wherein the VPTD peptide represented as SEQ ID NO: 1 or the HPTD peptide represented as SEQ ID NO: 2 is composed of D-type or L-type amino acids and contains one or more amino acids selected from the group consisting of arginine, lysine and histidine in an amount of 70-80%. 
     
     
         5 . A contrast agent for cancer diagnosis having cancer selective translocation function, which comprises VPTD peptide represented as SEQ ID NO: 1 or HPTD peptide represented as SEQ ID NO: 2 to which a fluorescent substance is bound. 
     
     
         6 . The contrast agent for cancer diagnosis having cancer selective translocation function of  claim 5 , wherein the fluorescent substance is selected from the group consisting of fluorescein isothiocyanate (FITC), radioisotopes, quantum dots, MRI contrast agents, fluorescein, tetramethylrhodamine, BODIPY, and Alexa. 
     
     
         7 . A composition for treating cancer having cancer selective translocation function, which comprises VPTD peptide represented as SEQ ID NO: 1 or HPTD peptide represented as SEQ ID NO: 2. 
     
     
         8 . A composition for enhancing cancer selective translocation, which comprises VPTD peptide represented as SEQ ID NO: 1 or HPTD peptide represented as SEQ ID NO: 2 as an active ingredient. 
     
     
         9 . A peptide having cancer selective translocation function-drug conjugate, which comprises a drug chemically linked to the N-terminus or C-terminus of VPTD peptide represented as SEQ ID NO: 1 or HPTD peptide represented as SEQ ID NO: 2. 
     
     
         10 . The peptide having cancer selective translocation function-drug conjugate of  claim 9 , wherein the VPTD peptide represented as SEQ ID NO: 1 or HPTD peptide represented as SEQ ID NO: 2 and the drug are linked to each other by a cysteine. 
     
     
         11 . The peptide having cancer selective translocation function-drug conjugate of  claim 9 , wherein the chemical linkage of the drug to the peptide is performed by any one crosslinking agent selected from the group consisting of 1,4-bis-maleimidobutane (BMB), 1,11-bis-maleimidotetraethyleneglycol (BM[PEO]4), 1-ethyl-3-[3-dimethyl aminopropyl]carbodiimide hydrochloride (EDC), succinimidyl-4-[N-maleimidomethylcyclohexane-1-carboxy-[6-amidocaproate]] (SMCC) and its sulfonate (sulfo-SMCC), succimidyl 6-[3-(2-pyridyldithio)-ropionamido]hexanoate (SPDP) and its sulfonate (sulfo-SPDP), m-maleimidobenzoyl-N-hydroxysuccinimide ester (MBS) and its sulfonate (sulfo-MBS), and succimidyl[4-(p-maleimidophenyl) butyrate] (SMPB) and its sulfonate (sulfo-SMPB). 
     
     
         12 . The peptide having cancer selective translocation function-drug conjugate of  claim 9 , wherein the drug is selected from the group consisting of an antisense oligonucleotide targeting RNA of a protein that causes a tumor or inflammatory disease, a siRNA targeting RNA of a protein that causes a tumor or inflammatory disease, an anticancer agent, an anticancer protein, an anti-inflammatory agent, an anti-inflammatory protein, an immune-enhancing protein, and a bone resorption inhibitor. 
     
     
         13 . The peptide having cancer selective translocation function-drug conjugate of  claim 12 , wherein the protein that causes a tumor or inflammatory disease is selected from the group consisting of vascular endothelial growth factor (VEGF), B-cell leukemia/lymphoma 2 (BCL2), epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), Janus kinase (JAN), and phosphatidylinositol-3-kinase/Akt kinase (PI3-K/AKT). 
     
     
         14 . A composition for treating cancer comprising a peptide having cancer selective translocation function-drug conjugate, which comprises a drug chemically linked to the N-terminus or C-terminus of VPTD peptide represented as SEQ ID NO: 1 or HPTD peptide represented as SEQ ID NO: 2. 
     
     
         15 . The composition for treating cancer of  claim 14 , wherein the drug is selected from the group consisting of an anticancer agent, an anticancer protein, an antisense oligonucleotide targeting RNA of a protein that cause a tumor, and a siRNA targeting RNA of a protein that cause a tumor. 
     
     
         16 . A drug delivery system having cancer selective translocation function, which comprises a drug linked to the N-terminus or C-terminus of VPTD peptide represented as SEQ ID NO: 1 or HPTD peptide represented as SEQ ID NO: 2. 
     
     
         17 . The drug delivery system having cancer selective translocation function of  claim 16 , wherein the drug is selected from the group consisting of an antisense oligonucleotide targeting RNA of a protein that causes a tumor or inflammatory disease, a siRNA targeting RNA of a protein that causes a tumor or inflammatory disease, an anticancer agent, an anticancer protein, an anti-inflammatory agent, an anti-inflammatory protein, an immune-enhancing protein, and a bone resorption inhibitor.