KR101757176B1 - Peptide probe for detecting colon cancer - Google Patents
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- KR101757176B1 KR101757176B1 KR1020150113440A KR20150113440A KR101757176B1 KR 101757176 B1 KR101757176 B1 KR 101757176B1 KR 1020150113440 A KR1020150113440 A KR 1020150113440A KR 20150113440 A KR20150113440 A KR 20150113440A KR 101757176 B1 KR101757176 B1 KR 101757176B1
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- G01N33/60—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving labelled substances involving radioactive labelled substances
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Abstract
The present invention relates to a peptide probe for the detection of colorectal cancer, which can form an imaging probe by combining a peptide specifically binding to colon cancer with a substance for colon cancer imaging. Such an imaging probe is small in size, So that effective imaging is possible.
Description
The present invention relates to a peptide probe capable of simultaneous diagnosis and treatment of colorectal cancer.
Colon cancer is most commonly adenocarcinoma, and is divided into colon cancer and rectal cancer. The incidence of each site is highest in the lower colon, or rectum, about 50%. Recent studies have shown that the incidence of diabetes habits and the mortality rate associated with colorectal cancer have increased dramatically in Korea. The cause of colorectal cancer is still unclear, but dietary habits and inflammatory bowel disease associated with genetic factors, intake of high fat and low fiber foods are being considered. Colorectal cancer can occur in all age groups, but it increases with age and occurs more frequently in the 50s and 60s. The incidence of men and women is somewhat higher in women with colon cancer and men with rectal cancer.
The treatment of colorectal cancer is based on surgical resection combined with chemotherapy and radiation therapy. It is known that progression of surgical treatment, chemotherapy, and radiation therapy is progressing to other organs due to the characteristics of colorectal cancer progressing without specific symptoms, and it is known that when the operation time is missed, the mortality rate is high. The 5-year mean survival rate was reported to be over 90% in stage I, more than 70% in stage II, more than 50% in stage III, less than 5% in stage IV, early detection of colorectal cancer The survival rate was significantly increased with treatment. Therefore, a method for early diagnosis of colon cancer is urgently required.
Early diagnosis of cancer was based on external changes of the biotissue due to the growth of cancer cells. Recently, however, diagnosis using biomolecules such as blood, glycocyte, DNA, And detection has been attempted. However, the most commonly used cancer diagnosis method is a tissue sample obtained through biopsy or an image diagnosis. Among them, biopsy results in great pain for the patient, which is not only costly but also takes a long time to diagnose. In addition, when the patient is actually cancerous, there is a risk that cancer metastasis may be induced during the biopsy, and in the case where a tissue sample can not be obtained through biopsy, It is impossible to diagnose the disease until the removal of the disease. In the diagnosis using imaging, cancer is judged based on X-ray image, nuclear magnetic resonance (NMR) image obtained using a contrast agent having a disease target substance, and the like. However, there is a possibility of misdiagnosis according to the skill of the clinician or the reader, and this image diagnosis has a disadvantage that it depends greatly on the precision of the device for obtaining the image. Furthermore, even the most precise apparatus can not detect tumors of a few mm or less, which is difficult to detect in the early stages of onset. In addition, in order to obtain an image, a patient or a disease-capable person is exposed to electromagnetic waves of high energy capable of causing mutation of a gene, so that it can not only cause another disease but also has a disadvantage in that the number of diagnosis through imaging is limited .
In particular, colon cancer is a common cancer with a worldwide incidence rate of less than 3, and the possibility of treatment is greatly influenced by the stage of cancer. In other words, it has a very high cure rate when it is detected at early stage through early diagnosis. Therefore, it is common to recognize the disease by the color change of the feces due to hemorrhage, and the patient or the person having the disease can be examined even though the diagnosis of the disease is important and the abnormality accompanying the cancer progresses is small. Observation through colonoscopy is common and biopsy should be performed for accurate disease identification. In summary, early diagnosis of colon cancer is important, and colonoscopy and biopsy are time-consuming, costly, inconvenient, and painful. Therefore, diagnostic methods that can dramatically reduce the number of unnecessary colonoscopy and biopsy specimens Is required.
Therefore, it would be very useful for patients if a new molecular approach could be used to screen colon cancer at an early stage.
It is an object of the present invention to provide a peptide that specifically binds to colon cancer cells or tissues.
Another object of the present invention is to provide a probe for colon cancer imaging comprising the above peptide.
It is another object of the present invention to provide a pharmaceutical use of the probe for colorectal cancer imaging in the diagnosis and treatment of colorectal cancer.
In order to accomplish the above object, the present invention provides a colorectal cancer-screening peptide represented by any one of amino acid sequences selected from the group consisting of SEQ ID NOS: 1 to 3.
The present invention also provides a probe for colorectal cancer imaging comprising a colorectal cancer-screening peptide represented by any one of the amino acid sequences selected from the group consisting of SEQ ID NOS: 1 to 3.
The present invention also provides a composition for diagnosing colorectal cancer comprising the above-described probe for colon cancer imaging.
The present invention also provides a colon cancer-tagged peptide represented by any one of the amino acid sequences selected from the group consisting of SEQ ID NOS: 1 to 3; And
There is provided a composition for treating colorectal cancer comprising a pharmaceutically active ingredient.
The present invention provides a peptide specifically binding to colon cancer, wherein the peptide binds to a material for colon cancer imaging to form an imaging probe. The peptide is small in size and easy to penetrate into the mucous membrane and is easy to produce. have.
1 is a schematic view of a colon cancer imaging process according to the present invention.
Fig. 2 shows a screening process of a colon cancer-specific peptide of the present invention.
FIG. 3 shows the results of screening three kinds of phage clones having the ability to bind to colon cancer cell lines obtained in the process of screening for the colon cancer-specific peptides of the present invention.
FIG. 4 is a photograph showing the binding affinity of a phage clone obtained in the colon cancer-specific peptide screening process of the present invention with a colon cancer cell line. FIG.
Figs. 5 to 8 are enlarged photographs of the results of Fig. 4 (enlargement ratio 400x).
FIG. 9 shows a sequence of a peptide having a binding ability to a colon cancer cell line obtained in the process of screening a colon cancer-specific peptide of the present invention.
FIG. 10 shows the binding affinity of conventional colon cancer-specific peptides to colon cancer and other types of cancer cell lines.
Fig. 11 shows the binding process of the photosensitizer with the colorectal cancer-specific peptide L20 of the present invention.
Fig. 12 shows a MALDI-TOF mass spectrum of a colorectal cancer-specific peptide to which the photosensitizer is incorporated according to the present invention.
Fig. 13 shows the binding affinity of a photosensitizer-coupled colon cancer-specific peptide of the present invention to a colon cancer cell line.
FIG. 14 shows photodynamic therapy effects of the photosensitizer-coupled colon cancer-specific peptide of the present invention.
Hereinafter, the configuration of the present invention will be described in detail.
The present inventors have found that a phage display library containing a 12-mer random peptide sequence is reacted with various colon cancer cell lines several times to select peptides specific for colon cancer cell lines, and then confirmed through sequencing, Through screening of phage display library screening for colon cancer - specific peptides, we screened for peptides specific for colon cancer. In addition, the present invention has been accomplished by confirming that the peptide specific for colon cancer can be used for effective drug delivery.
Accordingly, the present invention relates to a colon cancer-labeled peptide represented by any one of the amino acid sequences selected from the group consisting of SEQ ID NOS: 1 to 3.
In addition, the present invention provides a probe for colorectal cancer imaging comprising the above-mentioned peptide for colon cancer marking.
The present invention also provides a composition for diagnosing colorectal cancer comprising the above-described probe for colon cancer imaging.
The peptide of the present invention is a low molecular peptide composed of 12 amino acids selected through phage display library screening. It is small in size and is three-dimensionally stabilized, passes easily through the mucosa, There is an appreciable advantage. In addition, since the low molecular peptide according to the present invention secures stability through local injection and minimizes immunoreactivity, it has an advantage of early diagnosis of cancer. The low molecular peptide according to the present invention is relatively simple and less toxic than the antibody in the mass production. In addition, the low molecular peptide according to the present invention has a high binding strength to a target substance rather than an antibody, and does not undergo denaturation during thermal / chemical treatment. Also, because of its small size, it can be used as a fusion protein by attaching it to other proteins. It can be used as a diagnostic kit and a drug delivery material because it can be specifically attached to a polymer protein chain.
The above-mentioned " phage display library screening "method is a molecular technology for allowing an exogenous protein to be expressed on the surface of phage particles. When the phage library is incubated in colorectal cancer cells for a predetermined time and then washed, . These phage clones can be eluted through low pH or trypsin digestion and then infected with E. coli again to proliferate clones that bind to the antigen. Repeat the above procedure to obtain a peptide having the target antigen selectivity in the library The ratio is increased so that the peptide that specifically binds to colon cancer cells is selected.
The peptides of the present invention can be readily prepared by chemical synthesis known in the art (Creighton, Proteins, Structures and Molecular Principles, W. H. Freeman and Co., NY, 1983). Typical methods include liquid or solid phase synthesis, fractional condensation, F-MOC or T-BOC chemistry (see, for example, Chemical Approaches to the Synthesis of Peptides and Proteins, Williams et al., Eds., CRC Press, Boca Raton Florida A Practical Approach, Atherton & Sheppard, Eds., IRL Press, Oxford, England, 1989).
The peptides of the present invention can also be produced by genetic engineering methods. First, a DNA sequence encoding the peptide is constructed according to a conventional method. DNA sequences can be constructed by PCR amplification using appropriate primers. Alternatively, the DNA sequence may be synthesized by standard methods known in the art, for example, using an automated DNA synthesizer (e.g., marketed by Biosearch or Applied Biosystems). The constructed DNA sequence is operatively linked to the DNA sequence and contains one or more expression control sequences (e.g., promoters, enhancers, etc.) that regulate the expression of the DNA sequence , And the host cells are transformed with the recombinant expression vector formed therefrom. The resulting transformant is cultured under appropriate medium and conditions so that the DNA sequence is expressed, and the substantially pure peptide encoded by the DNA sequence is recovered from the culture. The recovery can be performed using methods known in the art (e.g., chromatography). By "substantially pure peptide" herein is meant that the peptide according to the invention is substantially free of any other proteins derived from the host.
The coding DNA sequence used for the peptide synthesis may be the sequence described in SEQ ID NOs: 4 to 6.
In order to easily identify, detect and quantify whether the peptide of the present invention binds to colorectal cancer tissue, the peptide of the present invention may be provided in a labeled state as shown in FIG. That is, they may be provided by linking (e.g., covalently binding or bridging) to a detectable label. The detectable label is a chromogenic enzyme (e.g., peroxidase (peroxidase), alkaline phosphatase (alkaline phosphatase)), radioactive isotopes (for example: 124 I, 125 I, 111 In, 99 mTc, 32 P, 35 S), Fluorescent materials such as FITC, RITC, rhodamine, cyanine, Texas Red, fluorescein, phycoerythrin, quantum dots), luminescent materials , A photosensitizer, and the like.
The photosensitizer may be a porphyrin series (Photofrin®, Levulan®, Metvix®, Visudyn®, etc.) or a chlorine series (Foscan®, Laserphyrin®, etc.) photosensitizer.
Similarly, the detectable label may be an antibody epitope, a substrate, a cofactor, an inhibitor or an affinity ligand. Such labeling may be performed during the synthesis of the peptide of the present invention, or may be performed in addition to the peptide already synthesized. If a fluorescent substance is used as a detectable marker, colorectal cancer can be diagnosed by fluorescence tomography (FMT). For example, the peptide of the present invention labeled with a fluorescent substance can be circulated into the blood and the fluorescence by the peptide can be observed by fluorescence tomography. If fluorescence is observed, it is diagnosed as colon cancer.
In addition, the peptide of the present invention can be used as a molecular image probe by combining diagnostic probes for image reading.
The diagnostic probe may be a T1 magnetic resonance imaging probe, an optical diagnostic probe, a CT diagnostic probe, or a radioactive isotope.
More specifically, T1 magnetic resonance imaging probes include Gd (III), Mg (II), Mn (III), Cr (III), Fe (II) ), Cu (II), 213 Bi, 212 Bi, 212 Pb, 225 Ac, 111 In, 90 Y, 67 Cu, 64 Cu, 66 Ga, 86 Y, 89 Zr, 67 Ga and lanthanoid 57 - 71)) can be used as the radioactive metal ion. The lanthanides include Pr (Ⅲ), Nd (Ⅲ ), Sm (Ⅲ), Yb (Ⅲ), Tb (Ⅲ), Dy (Ⅲ), Ho (Ⅲ), Er (Ⅲ), 177 Lu, 166 Ho , Or 153 Sm. Depending on the type of the radioactive metal ion, the molecular imaging technique that can use the complex molecular imaging probe is different. The radioactive metal ions that can be used for MRI are Gd (III), Mg (II), Mn (III), Cr (III), Fe (II), Fe (III), Co (II) (II), Pr (III), Nd (III), Sm (III), Yb (III), Tb (III), Dy (III), Ho (III) and Er (III). A radioactive metal ion that can be used in PET are 213 Bi, 212 Bi, 212 Pb , 225 Ac, 111 In, 90 Y, 67 Cu, 64 Cu, 66 Ga, 86 Y, 89 Zr, 67 Ga, 177 Lu, 166 Ho, or 153 Sm. For use as an X-ray contrast agent, the radioactive metal ion should be capable of absorbing an appropriate amount of X-rays (i.e., radioactive impermeable), such as indium, iodine, and the like.
As optical diagnostic probes, organic fluorescent dyes, quantum dots, dye-coated inorganic supports (for example, SiO 2 , Al 2 O 3 ) and the like can be used.
The CT diagnostic probes can be nanoparticles or iodine compounds selected from the group consisting of silica nanoparticles, silver nanoparticles, gold nanoparticles, and iron oxide nanoparticles.
As the radioisotope, In, Tc, F and the like can be used.
When used as the molecular imaging probe, the T1 magnetic resonance imaging and the T1 magnetic resonance imaging can be simultaneously performed by combining the T1 magnetic resonance imaging probe. When the optical diagnostic probe is combined, the magnetic resonance imaging and the optical imaging can be performed at the same time , Combined with a CT diagnostic probe, both magnetic resonance imaging and CT diagnosis can be performed simultaneously. In addition, when combined with radioisotope, MRI, PET, and SPECT can be performed simultaneously.
The peptide of the present invention exhibits target-specificity that specifically binds to colon cancer cells or tissues, and thus can be used as a drug delivery vehicle for selectively delivering drugs. Such drugs can be used for the treatment of colorectal cancer by chemically, physically sharing, or non-covalent binding, either directly or by the selective introduction into colon cancer cells or tissues using other mediators.
Accordingly, the present invention provides a colon cancer-screening peptide represented by any one of the amino acid sequences selected from the group consisting of SEQ ID NOS: 1 to 3; And a composition for treating colorectal cancer, which comprises a pharmaceutically active ingredient.
The composition for treating colorectal cancer of the present invention may use a form in which a photosensitizer is combined with a peptide for photodynamic therapy.
The types of the photo-sensitizers are as described above.
In addition, when the peptide of the present invention is used in combination with a conventionally known drug to treat cancer, the peptide of the present invention selectively transmits the drug only to cancer tissues and cancer cells, thereby increasing the efficacy of the drug. The side effects of the drug can be significantly reduced.
The pharmaceutical active ingredient may be administered orally or parenterally without any particular limitation including siRNA, antisense, anticancer, antibiotic, hormone, hormone antagonist, interleukin, interferon, growth factor, tumor necrosis factor, endotoxin, lymphotoxin, urokinase, A tyrosine kinase, a tissue plasminogen activator, a protease inhibitor, an alkylphosphocholine, a radioactive isotope labeled component, a cardiovascular drug, a gastrointestinal drug, or a nervous system drug.
Preferably, the pharmaceutically active ingredient may be an anti-cancer agent. The anticancer agent that is linked to the peptide of the present invention can be used without limitation as long as it is conventionally used in the treatment of colorectal cancer. The linkage between the anticancer agent and the peptide of the present invention can be carried out by a method known in the art, for example, through covalent bonding, crosslinking and the like. For this purpose, the peptide of the present invention can be chemically modified to the extent that its activity is not lost if necessary.
The composition for diagnosing or treating colorectal cancer of the present invention further comprises a pharmaceutically acceptable carrier. Such pharmaceutically acceptable carriers include, for example, excipients, diluents, and the like, which are well known in the art. The choice of carrier may be determined by the particular formulation to be prepared and the particular mode of administration of the composition. Accordingly, the composition for diagnosing or treating colorectal cancer of the present invention can exist in a wide variety of forms. The composition for diagnosing or treating colorectal cancer of the present invention may be administered by an appropriate administration method depending on the use thereof or the kind of the active ingredient. The kind of the pharmaceutical composition, the carrier required for the preparation of the formulation, the administration method, the dosage, and the like can be appropriately determined by those skilled in the art.
The dose of the composition for diagnosing or treating colorectal cancer of the present invention may vary depending on the type of disease to be diagnosed or treated, the degree of disease, the target tissue or organ to be diagnosed, and the characteristics of the diagnostic apparatus, May be increased or decreased depending on the age, sex, body weight, race, etc. of the subject to be administered.
A preferred method of administration of the composition for diagnosing or treating colorectal cancer of the present invention is parenterally, for example, bolus injection, intravenous injection, intramuscular injection, or spraying if the lung is to be contrasted, for example, Oral or rectal administration may be used, but it is also possible to use a known method of administration of contrast medium. Parenteral dosage forms should be sterile and free of physiologically unacceptable and parasitic, superparamagnetic, ferromagnetic, or quasi-ferromagnetic contaminants, and preservatives, antimicrobial agents, buffers and antioxidants commonly used in parenteral solutions, May contain excipients and may further contain other optional additives which do not interfere with the molecular imaging.
Hereinafter, the present invention will be described in detail with reference to examples. However, the following examples are illustrative of the present invention, and the present invention is not limited by the following examples.
≪ Example 1 > Screening of colon cancer-specific peptides
Colon cancer specific peptides were screened through phage display library screening. Ph.D.-12 ™ phage display peptide library from New England BioLabs (NEB) was used. The library of about 10 11 12-mer random peptide sequence.
The colorectal cancer cell line SW480, HCT116, HT29, LoVo and DLD1 used in the screening process were purchased from ATCC (American Type Culture Collection, USA), and 10% fetal bovine serum (FBS) and 2 mM L-glutamine And cultured in RPMI medium at 37 ° C and 5% CO 2 .
The cultured cell line and phage display peptide library were incubated at room temperature for 1 hour in an incubator, and then cells were separated through a centrifuge. Cells were washed three times with PBS. To remove the phage attached to the cells, 0.1M Glycine (pH 2.2) / 10.9% NaCl solution was added. A 1.5 M Tris (pH 8.8) solution was added to neutralize the separated phages. Neutralized phage were amplified by inoculation into their host E. coli cell, ER2738. The above panning procedure was repeated three times and the phages obtained in the third panning procedure were plated on a plate medium to obtain a phage. Each of the phage plaques generated on the plate was inoculated into ER2738 and amplified, followed by salting out to separate the phage. The separated phages were placed in a 96-well plate in a colon cancer cell line and reacted for 2 hours. After washing three times with a washing solution (PBS / 0.05% Triton X-100), M13-Phage HRP antibody (abcam, UK) And then washed three times. TMB solution was added to react with HRP, neutralized by adding sulfuric acid solution, and absorbance was measured at 450 nm using a spectrophotometer (Biotek, USA). As a result of ELISA, phages that did not adhere to normal cell lines and only reacted with colon cancer cells were selected.
A total of 16 libraries were selected through the third selection process (Fig. 2).
Through the screening of the phage display library, three kinds of phage clones having binding ability only to a colon cancer cell line without binding to a normal cell line were found (see FIG. 3).
Immunocytochemistry was performed to confirm the binding ability of the three selected phage clones to colon cancer cell lines. For this purpose, 1 × 10 5 colon cancer cell lines were seeded on a culture plate for immunocytochemical experiments and cultured for 24 hours. The cultured cells were washed twice with PBS, fixed in 50% methanol / 50% acetone, and reacted at 4 ° C for 15 minutes. After washing twice with PBS, the cells were incubated in a blocking solution (10% BSA, 5% FBS / PBS) for 30 minutes. Then, 10 μM of FITC-conjugated peptide solution was added to the solution for 1 hour. After washing three times with PBS, they were observed under a fluorescence microscope.
As shown in FIGS. 4 to 8, the ability to bind to the normal cell line (CCD-18Co) was low and the cell line exhibited high binding capacity.
The peptide sequences of the three selected phage clones were analyzed and confirmed as the sequence of FIG.
≪ Comparative Example 1 > Binding Affinity of Colon Cancer-Specific Peptide
Conventional colon cancer specific peptides were obtained by requesting synthesis of peptone (Korea).
To investigate the binding ability of existing colon cancer - specific peptides, we applied them to immunocytochemical experiments. 1 × 10 5 colon cancer cell lines were seeded on a culture plate for immunocytochemical experiments, cultured for 24 hours, washed twice with PBS, fixed in 50% methanol / 50% acetone, and reacted at 4 ° C. for 15 minutes. After washing twice with PBS, the cells were incubated in a blocking solution (10% BSA, 5% FBS / PBS) for 30 minutes. Then, 10 μM of FITC-conjugated peptide solution was added to the reaction mixture for 1 hour. After washing three times with PBS, they were observed under a fluorescence microscope.
As shown in FIG. 10, the binding affinity of the QPI peptide showed that conventional colon cancer-specific peptides showed binding not only in colon cancer but also in other cancers.
Example 2 Production of Colon Cancer-Specific Peptide-Photo Sensitive Probe
The binding ability of the selected peptide (L20, see FIG. 9) using the colorectal cancer cell line to the photosensitizer hematoporphyrin (HPP) was examined by immunocytochemistry.
The production process of the hematoporphyrin-bound peptide L20 is shown in Fig. 11, and the final compound was confirmed by MALDI-TOF mass spectrometry (Fig. 12).
The binding ability of L20-HPP in the colon cancer cell line was confirmed, indicating that the selectivity for cancer cells and the intracellular uptake of HPP were increased through the binding of peptide L20 (FIG. 13).
MTT assay (3- (4,5-Dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide assay) was performed to confirm the therapeutic effect of the peptide-photosensitizer. For this, 2x10 4 colon cancer cell lines were seeded in a 96-well cell culture plate and cultured for 24 hours. The photosensitizer not associated with the peptide was treated with light (50 J / cm 2 ) with a 630 nm laser for 1 hour or 12 hours. After 12 hours, MTT reagent was added and reacted for 4 hours. After removal of all the drugs, DMSO was added and absorbance was measured at 470 nm using a spectrometer reader.
As shown in Fig. 14, the peptide-photosensitizer has been shown to increase the photodynamic therapeutic effect and increase the selectivity of the photosensitizer.
<110> CATHOLIC UNIVERSITY INDUSTRY ACADEMIC COOPERATION FOUNDATION <120> Peptide probe for detecting colon cancer <130> P14U11C1750 <160> 6 <170> Kopatentin 2.0 <210> 1 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Peptide L16 specific colon cancer <400> 1 Glu Phe Val Ile Glu Thr Phe Tyr Met Val Gln Arg 1 5 10 <210> 2 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Peptide L20 specific colon cancer <400> 2 Ala Asn Leu Asn Leu Trp Thr Asp Tyr Ile Arg Trp 1 5 10 <210> 3 <211> 12 <212> PRT <213> Artificial Sequence <220> <223> Peptide S15 specific colon cancer <400> 3 Ser Leu Val His Pro Ser Tyr Leu Val Asp Tyr Leu 1 5 10 <210> 4 <211> 36 <212> DNA <213> Artificial Sequence <220> <223> Peptide L16 encoding sequence <400> 4 gagtttgtta ttgagacgtt ttatatggtg cagagg 36 <210> 5 <211> 36 <212> DNA <213> Artificial Sequence <220> <223> Peptide L20 encoding sequence <400> 5 gcgaatctga atttgtggac tgattatatt aggtgg 36 <210> 6 <211> 36 <212> DNA <213> Artificial Sequence <220> <223> Peptide S15 encoding sequence <400> 6 tctttggttc atccttctta tctggtggat tatctt 36
Claims (11)
Wherein the peptide is labeled with one selected from the group consisting of a chromogenic enzyme, a radioactive isotope, a fluorescent substance, a luminescent substance, and a photosensitizer.
The photosensitizer is a porphyrin-based or chlorine-based photosensitizer, a probe for colon cancer imaging.
A probe for colon cancer imaging wherein the peptide is a further combined diagnostic probe for imaging.
Gd (Ⅲ), Mg (Ⅱ ), Mn (Ⅲ), Cr (Ⅲ), Fe (Ⅱ), Fe (Ⅲ), Co (Ⅱ), Ni (Ⅱ), Cu (Ⅱ), 213 Bi, 212 Bi A radioactive metal ion selected from the group consisting of 212 Pb, 225 Ac, 111 In, 90 Y, 67 Cu, 64 Cu, 66 Ga, 86 Y, 89 Zr, 67 Ga and lanthanide; And
A probe for colon cancer imaging, comprising nanoparticles selected from the group consisting of silica nanoparticles, silver nanoparticles, gold nanoparticles, and iron oxide nanoparticles.
Wherein the photosensitizer is a porphyrin-based or chlorine-based photosensitizer.
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