Albumin conjugate, method for preparing same, and composition for targeting, diagnosing or treating cancer comprising same

Abstract

Provided is an albumin binder represented by Chemical Formula 1: In Chemical Formula 1, A is a group excluding an amine group in albumin, and Z, R11 to R14, R21 to R24, R3 to R6, and m are each see the content described in the specification. Lt; chemical formula 1gt;

Description

Technical Field

[0001] The invention relates to an albumin binder, a preparation method thereof and a composition comprising the same for targeting, diagnosing or treating cancer. Background Art

[0002] Human serum albumin (HSA) is present in human blood at concentrations ranging from approximately 35 g / L to 55 g / L. It is used to transport substances essential for life. Albumin is a stable protein with a half-life of approximately 19 days. Cancers (cancer cells and / or cancerous tissues) can obtain nutrients necessary for growth through albumin. Cancers may possess albumin receptors, such as gp18, gp60, and SPARC, to utilize albumin. Cancers can attract albumin through albumin receptors, and as cancer grows, albumin concentrations in the blood decrease. Research is underway to utilize these properties to bind anticancer agents to albumin in order to deliver them to cancer cells and / or cancerous tissues.

[0003] Albumin-paclitaxel is a simple mixture of albumin and an anticancer agent (e.g., paclitaxel). However, there are problems with this approach, as the anticancer agent simply mixed with albumin may initially be excessively released, and it is difficult to control how the albumin binds to the anticancer agent, making it difficult to ensure reproducibility.

[0004] Maleimide can be used to covalently bond albumin to anticancer agents (e.g., doxorubicin). Maleimide binds to the anticancer agent and covalently bonds to the -SH residue at cysteine-34 of albumin. However, maleimide is unstable due to pH, and the -SH residue at cysteine-34 of albumin can be oxidized (e.g., outside the body). Maleimide also suffers from its unstable ring structure, making it susceptible to degradation over time. Therefore, a stable bond between albumin and the anticancer agent is required. Summary of the Invention

[0005] Technical issues

[0006] In one aspect, a combination of an anticancer agent and albumin is provided, which has high reproducibility and high stability.

[0007] In one aspect, an albumin binder is provided that can be used to target, diagnose or treat cancer.

[0008] On the other hand, a method for preparing the albumin conjugate is provided.

[0009] Yet another aspect provides a composition for targeting, diagnosing or treating cancer, comprising the albumin binder.

[0010] In another aspect, a composition for targeting, diagnosing or treating cancer is provided, comprising a boron-containing compound.

[0011] Technical Solution

[0012] According to one aspect, an albumin binder represented by the following Chemical Formula 1 is disclosed:

[0013] <Chemical Formula 1>

[0014]

[0015] In the chemical formula 1,

[0016] A is a group that excludes the amine group in albumin,

[0017] Z is N, O or C(R 14 ),

[0018] R 11 to R 14 、R 21 to R 24 and R3 to R6 are each independently selected from hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, formyl, carboxyl, amidino, hydrazine, hydrazide, substituted or unsubstituted C1-C 10 Alkyl, substituted or unsubstituted C2-C 10 Alkenyl, substituted or unsubstituted C2-C 10 Alkynyl, substituted or unsubstituted C1-C 10 Alkoxy, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C1-C 10 Heterocycloalkyl, substituted or unsubstituted C3-C 10 Cycloalkenyl, substituted or unsubstituted C1-C 10 Heterocycloalkenyl, substituted or unsubstituted C6-C 20 Aryl, substituted or unsubstituted C6-C 20 Aryloxy, substituted or unsubstituted C6-C 20 Arylthio, substituted or unsubstituted C1-C 20 heteroaryl, -Si(Q1)(Q2)(Q3), -N(Q1)(Q2), -B(Q1)(Q2), -C(=O)(Q1), -S(=O)2(Q1) and -P(=O)(Q1)(Q2),

[0019] Optionally, i) R 11 and R 12 ii) R 12 and R 13 iii) R 13 and R 14iv) R 21 and R 22 ,v)R 22 and R 23 ,ⅵ)R 23 and R 24 or vii) any combination thereof is combined with each other to form a substituted or unsubstituted C3-C 10 Carbocyclic group or substituted or unsubstituted C1-C 10 Heterocyclic groups,

[0020] m is an integer selected from 1 to 5,

[0021] Q1 to Q3 are independently selected from

[0022] hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, amidino, hydrazine, hydrazide; and

[0023] C1-C2-substituted or unsubstituted by hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, amidino, hydrazine, hydrazine or any combination thereof 10 Alkyl, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C1-C 10 Alkoxy, C3-C 10 Cycloalkyl, C1-C 10 Heterocycloalkyl, C3-C 10 Cycloalkenyl, C1-C 10 Heterocycloalkenyl, C6-C 20 Aryl and C1-C 20 Heteroaryl.

[0024] According to another aspect, a method for preparing the albumin conjugate is disclosed, which comprises the step of reacting a boron-containing compound represented by the following Chemical Formula 2 with albumin:

[0025] <Chemical Formula 2>

[0026]

[0027] In the chemical formula 2,

[0028] Z is N, O or C(R 14 ),

[0029] R 11 to R 14 、R 21 to R 24 and R3 to R6 are each independently selected from hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, formyl, carboxyl, amidino, hydrazine, hydrazide, substituted or unsubstituted C1-C 10Alkyl, substituted or unsubstituted C2-C 10 Alkenyl, substituted or unsubstituted C2-C 10 Alkynyl, substituted or unsubstituted C1-C 10 Alkoxy, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C1-C 10 Heterocycloalkyl, substituted or unsubstituted C3-C 10 Cycloalkenyl, substituted or unsubstituted C1-C 10 Heterocycloalkenyl, substituted or unsubstituted C6-C 20 Aryl, substituted or unsubstituted C6-C 20 Aryloxy, substituted or unsubstituted C6-C 20 Arylthio, substituted or unsubstituted C1-C 20 heteroaryl, -Si(Q1)(Q2)(Q3), -N(Q1)(Q2), -B(Q1)(Q2), -C(=O)(Q1), -S(=O)2(Q1) and -P(=O)(Q1)(Q2),

[0030] Optionally, i) R 11 and R 12 ii) R 12 and R 13 iii) R 13 and R 14 iv) R 21 and R 22 ,v)R 22 and R 23 ,ⅵ)R 23 and R 24 or vii) any combination thereof is combined with each other to form a substituted or unsubstituted C3-C 10 Carbocyclic group or substituted or unsubstituted C1-C 10 Heterocyclic groups,

[0031] m is an integer selected from 1 to 5,

[0032] Q1 to Q3 are independently selected from

[0033] hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, amidino, hydrazine, hydrazide; and

[0034] C1-C2-substituted or unsubstituted by hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, amidino, hydrazine, hydrazine or any combination thereof 10 Alkyl, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C1-C 10 Alkoxy, C3-C 10Cycloalkyl, C1-C 10 Heterocycloalkyl, C3-C 10 Cycloalkenyl, C1-C 10 Heterocycloalkenyl, C6-C 20 Aryl and C1-C 20 Heteroaryl.

[0035] According to yet another aspect, disclosed is a composition for targeting, diagnosing or treating cancer, comprising the albumin binder or the boron-containing compound.

[0036] Beneficial effects

[0037] The boron-containing compound represented by Chemical Formula 2 can stably bind to albumin to form an albumin-binding compound represented by Chemical Formula 1. The albumin-binding compound can selectively accumulate in cancer cells within an individual, thereby targeting cancer cells and / or cancerous tissue. The albumin-binding compound can exhibit fluorescent properties, enabling visualization of cancerous tissue (fluorescence imaging). When irradiated with light, the albumin-binding compound generates reactive oxygen species (ROS), thereby enabling cancer treatment. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] Figure 1 The X-ray crystal structure of an albumin conjugate according to one embodiment of the present invention is shown.

[0039] Figure 2 Graph showing changes in fluorescence intensity measured with increasing albumin concentration in boron-containing compounds and the dissociation constant calculated based on the changes.

[0040] Figures 3a to 3c FIG. 5 shows the fluorescence intensity generated when the albumin conjugate according to one embodiment of the present invention is irradiated with light.

[0041] Figures 4a to 4c The fluorescence intensity generated when the boron-containing compound is irradiated with light is shown.

[0042] Figure 5a and Figure 5b Shown is the fluorescence intensity generated when light was irradiated without using an albumin binder and a boron-containing compound.

[0043] Figure 6 It will Figures 3a to 3c 、 Figures 4a to 4c 、 Figure 5a and Figure 5b The results shown are graphs of the differences in fluorescence intensity at specific wavelengths over time.

[0044] Figures 7a to 7dThis is a graph showing the difference in fluorescence intensity depending on the concentration of lysine mixed with the boron-containing compound.

[0045] Figure 8 The graph shows the results of observing the fluorescence characteristics of individuals after injection of albumin conjugates using bovine serum albumin and human serum albumin.

[0046] Figure 9a 、 Figure 9b 、 Figures 10a to 10c : is a graph showing the results of evaluating the cancer therapeutic ability of an albumin binder according to one embodiment of the present invention. DETAILED DESCRIPTION

[0047] Unless otherwise defined, all technical terms used in this specification have the same meaning as commonly understood by those skilled in the art. In addition, even if not specifically stated, the numerical values ​​described in this specification are deemed to include the meaning of "about".

[0048] In this specification, unless explicitly described otherwise, the term “comprising” is used to indicate that other constituent elements may be added and / or inserted, rather than excluding other constituent elements.

[0049] In this specification, the term "any combination" refers to a mixture or combination of one or more of the described constituent elements.

[0050] In this specification, the term "interaction" may be direct or indirect, and may include direct binding or indirect binding, and the binding may be mediated by other molecules.

[0051] In this specification, a substituent refers to an unsubstituted parent group induced by exchanging one or more hydrogen atoms for another atom or functional group. Unless otherwise specified, when a functional group is considered to be "substituted", it means that the functional group is substituted with one or more substituents selected from deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, amidino, hydrazine, hydrazide, alkyl having 1 to 40 carbon atoms, alkenyl having 2 to 40 carbon atoms, alkynyl having 2 to 40 carbon atoms, cycloalkyl having 3 to 40 carbon atoms, cycloalkenyl having 3 to 40 carbon atoms, aryl having 6 to 40 carbon atoms, and heteroaryl having 3 to 40 carbon atoms.

[0052] When a functional group is described as being "optionally substituted," this means that the functional group can be substituted with the substituent described.

[0053] In this specification, "a" and "b" in "carbon atoms a to b" refer to the number of carbon atoms in a specific functional group. That is, the functional group may include carbon atoms from a to b. For example, "alkylene group having 1 to 4 carbon atoms" refers to alkylene groups having 1 to 4 carbon atoms, i.e., -CH2-, -CH2CH2-, -CH2CH2CH2-, -(CH3)2C-, -CH2CH2CH2CH2-, -CH2CH2CH(CH3)-, and -(CH3)2C-.

[0054] In this specification, the term "alkyl" refers to a branched or unbranched aliphatic hydrocarbon. In one embodiment, the alkyl group may be substituted or unsubstituted. Alkyl groups include, but are not necessarily limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, and the like, and each of these groups may be optionally substituted or unsubstituted. In one embodiment, the alkyl group may have 1 to 6 carbon atoms. For example, an alkyl group having 1 to 6 carbon atoms may be methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, pentyl, 3-pentyl, hexyl, and the like.

[0055] In this specification, the term "alkenyl" refers to a branched or unbranched hydrocarbon having at least one carbon-carbon double bond. Non-limiting examples of alkenyl groups may include vinyl, allyl, butenyl, isopropenyl or isobutenyl.

[0056] In the present specification, the term "alkynyl" refers to a branched or unbranched hydrocarbon having at least one carbon-carbon triple bond.

[0057] In this specification, the term "alkoxy" refers to an alkyl group as defined above combined with an oxygen atom, which may include C1-C 20 Alkoxy groups, for example, may include methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy, nonyloxy, decyloxy, undecyloxy, dodecyloxy, tridecyloxy, tetradecyloxy, pentadecyloxy, hexadecyloxy, heptadecyloxy, octadecyloxy, nonadecyloxy, eicosyloxy or all possible isomers thereof, but are not limited thereto.

[0058] In the present specification, "cycloalkyl" is a form of a monovalent functional group having a saturated hydrocarbon ring, and may include C3-C8 cycloalkyl, for example, may include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl or all possible isomers thereof, but is not limited thereto.

[0059] As used herein, the term "aryl" refers to an aromatic ring, a ring system (i.e., two or more fused rings sharing two adjacent carbon atoms), or a plurality of aromatic rings linked to one another by a single bond, -O-, -S-, -C(=O)-, -S(=O)2-, -Si(Ra)(Rb)- (Ra and Rb are each independently an alkyl group having 1 to 10 carbon atoms), an alkylene group having 1 to 10 carbon atoms that is substituted or unsubstituted with a halogen, or -C(=O)-NH-, wherein the aryl group is a ring system. When the aryl group is a ring system, each ring in the system is aromatic. For example, aryl groups include, but are not limited to, phenyl, biphenyl, naphthyl, phenanthrenyl, naphthathenyl, and the like. The aryl group may be substituted or unsubstituted.

[0060] As used herein, the term "heteroaryl" refers to a monocyclic or bicyclic organic compound comprising one or more heteroatoms selected from N, O, P, or S, with the remaining ring atoms being carbon. The number of carbon atoms in the heteroaryl group is not particularly limited and may range from 2 to 60 carbon atoms. The heteroaryl group may be a structure of at least one selected from the group consisting of, for example, a substituted or unsubstituted imidazolyl group, a substituted or unsubstituted triazolyl group, a substituted or unsubstituted tetrazolyl group, a substituted or unsubstituted oxadiazolyl group, a substituted or unsubstituted oxatriazolyl group, a substituted or unsubstituted thiazolyl group, a substituted or unsubstituted benzimidazolyl group, a substituted or unsubstituted benzotriazolyl group, a substituted or unsubstituted pyridinyl group, a substituted or unsubstituted pyrimidinyl group, a substituted or unsubstituted triazinyl group, a substituted or unsubstituted pyrazinyl group, a substituted or unsubstituted pyridazinyl group, a substituted or unsubstituted quinoline group, a substituted or unsubstituted isoquinolyl group, a substituted or unsubstituted phthalazine group, a substituted or unsubstituted naphthyridine group, a substituted or unsubstituted quinoxaline group, a substituted or unsubstituted quinazoline group, a substituted or unsubstituted acridine group, a substituted or unsubstituted phenanthroline group, and a substituted or unsubstituted phenazine group, or a combination thereof.

[0061] According to one aspect, the albumin binder is represented by the following Chemical Formula 1:

[0062] <Chemical Formula 1>

[0063]

[0064] In Chemical Formula 1, A may be a group in albumin excluding an amine group. According to one embodiment, the amine group may be an amine group included in the side chain of lysine represented by the following Chemical Formula 3. According to another embodiment, the amine group may be an amine group included in the main chain of lysine represented by the following Chemical Formula 3.

[0065] <Chemical Formula 3>

[0066]

[0067] According to one embodiment, the amine group may be located at the SS1 site of albumin. For example, in Chemical Formula 1, A may be any group excluding the amine group of lysine located at the SS1 site of albumin. The lysine located at the SS1 site of albumin may be referred to as lysine-199 (Lysine-199 or Lys-199).

[0068] According to one embodiment, the albumin binder may include human serum albumin (HSA) or bovine serum albumin (BSA). That is, the albumin may be human serum albumin (HSA) or bovine serum albumin (BSA).

[0069] In the chemical formula 1, Z can be N, O or C (R 14 ), and R is described later below 14 According to one embodiment, Z may be C(R 14 ), but not limited to.

[0070] In the chemical formula 1, R 11 to R 14 、R 21 to R 24 and R3 to R6 can be each independently selected from hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, formyl, carboxyl, amidino, hydrazine, hydrazide, substituted or unsubstituted C1-C 10 Alkyl, substituted or unsubstituted C2-C 10 Alkenyl, substituted or unsubstituted C2-C 10 Alkynyl, substituted or unsubstituted C1-C 10 Alkoxy, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C1-C 10 Heterocycloalkyl, substituted or unsubstituted C3-C 10 Cycloalkenyl, substituted or unsubstituted C1-C 10 Heterocycloalkenyl, substituted or unsubstituted C6-C 20 Aryl, substituted or unsubstituted C6-C 20 Aryloxy, substituted or unsubstituted C6-C 20 Arylthio, substituted or unsubstituted C1-C 20heteroaryl, -Si(Q1)(Q2)(Q3), -N(Q1)(Q2), -B(Q1)(Q2), -C(=O)(Q1), -S(=O)2(Q1) and -P(=O)(Q1)(Q2), and Q1 to Q3 are described later hereinafter.

[0071] In the chemical formula 1, optionally, i) R 11 and R 12 ii) R 12 and R 13 iii) R 13 and R 14 iv) R 21 and R 22 ,v)R 22 and R 23 ,ⅵ)R 23 and R 24 or vii) any combination thereof is combined with each other to form a substituted or unsubstituted C3-C 10 Carbocyclic group or substituted or unsubstituted C1-C 10 Heterocyclic group, according to one embodiment, in the chemical formula 1, R 12 and R 13 Combined with each other to form substituted or unsubstituted C3-C 10 Carbocyclic group or substituted or unsubstituted C1-C 10 Heterocyclic groups include, but are not limited to, heterocyclic groups.

[0072] According to one embodiment, in the chemical formula 1, R 11 to R 14 At least one of -F, -Cl, -Br, -I, substituted or unsubstituted C1-C 10 Alkyl, substituted or unsubstituted C2-C 10 Alkenyl and substituted or unsubstituted C1-C 20 Alkoxy groups include, but are not limited to, alkoxy groups.

[0073] According to one embodiment, in the chemical formula 1, R 21 to R 24 They may be hydrogen, but are not limited thereto.

[0074] According to one embodiment, in the chemical formula 1, R3 can be selected from hydrogen, deuterium, substituted or unsubstituted C6-C 20 Aryl, but not limited thereto.

[0075] According to one embodiment, in the Chemical Formula 1, R4 may be a hydroxyl group, but is not limited thereto.

[0076] According to one embodiment, in the Chemical Formula 1, R5 to R6 may be hydrogen, but are not limited thereto.

[0077] In Chemical Formula 1, m may be an integer selected from 1 to 5. According to an embodiment, m may be 1, but is not limited thereto.

[0078] Q1 to Q3 are independently selected from

[0079] hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, amidino, hydrazine, hydrazide; and

[0080] C1-C2-substituted or unsubstituted by hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, amidino, hydrazine, hydrazine or any combination thereof 10 Alkyl, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C1-C 10 Alkoxy, C3-C 10 Cycloalkyl, C1-C 10 Heterocycloalkyl, C3-C 10 Cycloalkenyl, C1-C 10 Heterocycloalkenyl, C6-C 20 Aryl and C1-C 20 Heteroaryl.

[0081] According to one embodiment, the albumin binder may be any one of the following albumin binders B-A1 to B-A5, but is not limited thereto.

[0082]

[0083] In the albumin binders B-A1 to B-A5, A is the same as described in this specification.

[0084] According to one embodiment, the albumin binder may have fluorescent properties.

[0085] According to one embodiment, the albumin-binding body can generate reactive oxygen species under light irradiation.

[0086] According to another aspect, a method for preparing an albumin conjugate is disclosed, which includes the step of reacting a boron-containing compound represented by the following Chemical Formula 2 with albumin:

[0087] <Chemical Formula 2>

[0088]

[0089] In the chemical formula 2,

[0090] Z is N, O or C(R 14 ),

[0091] R 11 to R14 、R 21 to R 24 and R3 to R6 are each independently selected from hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, formyl, carboxyl, amidino, hydrazine, hydrazide, substituted or unsubstituted C1-C 10 Alkyl, substituted or unsubstituted C2-C 10 Alkenyl, substituted or unsubstituted C2-C 10 Alkynyl, substituted or unsubstituted C1-C 10 Alkoxy, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C1-C 10 Heterocycloalkyl, substituted or unsubstituted C3-C 10 Cycloalkenyl, substituted or unsubstituted C1-C 10 Heterocycloalkenyl, substituted or unsubstituted C6-C 20 Aryl, substituted or unsubstituted C6-C 20 Aryloxy, substituted or unsubstituted C6-C 20 Arylthio, substituted or unsubstituted C1-C 20 heteroaryl, -Si(Q1)(Q2)(Q3), -N(Q1)(Q2), -B(Q1)(Q2), -C(=O)(Q1), -S(=O)2(Q1) and -P(=O)(Q1)(Q2),

[0092] Optionally, i) R 11 and R 12 ii) R 12 and R 13 iii) R 13 and R 14 iv) R 21 and R 22 ,v)R 22 and R 23 ,ⅵ)R 23 and R 24 or vii) any combination thereof is combined with each other to form a substituted or unsubstituted C3-C 10 Carbocyclic group or substituted or unsubstituted C1-C 10 Heterocyclic groups,

[0093] m is an integer selected from 1 to 5,

[0094] Q1 to Q3 are independently selected from

[0095] From hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, amidino, hydrazine, hydrazine; and

[0096] C1-C2-substituted or unsubstituted by hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, amidino, hydrazine, hydrazine or any combination thereof 10 Alkyl, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C1-C 10 Alkoxy, C3-C 10 Cycloalkyl, C1-C 10 Heterocycloalkyl, C3-C 10 Cycloalkenyl, C1-C 10 Heterocycloalkenyl, C6-C 20 Aryl and C1-C 20 Heteroaryl.

[0097] In the chemical formula 2, Z and R 11 to R 14 、R 21 to R 24 , R3 to R6 and m are described in Chemical Formula 1, respectively. 11 to R 14 、R 21 to R 24 , R3 to R6 and m.

[0098] According to one embodiment, the boron-containing compound may be any one of the following compounds B1 to B5:

[0099] .

[0100] The method for preparing the albumin conjugate may include mixing the boron-containing compound represented by Chemical Formula 2 with human serum albumin (HSA).

[0101] According to one embodiment, in the chemical formula 2, boron (B) may react with the albumin to form a tetracoordinate boron (B). Specifically, tricoordinate boron (B) may react with the albumin to form a tetracoordinate boron (B).

[0102] According to one embodiment, the step of reacting the boron-containing compound with albumin can be performed outside the body of the individual.

[0103] According to one embodiment, the step of reacting the boron-containing compound with albumin can be performed in the blood of an individual. For example, the albumin is present in the blood of the individual, and the boron-containing compound is administered to the individual to react with the albumin. In other words, the albumin conjugate can be prepared in the body of the individual.

[0104] According to yet another aspect, disclosed is a composition for targeting, diagnosing or treating cancer, comprising the albumin binder or the boron-containing compound.

[0105] Examples of the cancer may include, but are not limited to, breast cancer, kidney cancer, testicular cancer, prostate cancer, ovarian cancer, uterine cancer, cervical cancer, vaginal cancer, fallopian tube cancer, rectal cancer, lung cancer, stomach cancer, liver cancer, esophageal cancer, small intestine cancer, pancreatic cancer, oral cancer, etc.

[0106] According to one embodiment, the albumin binder or the boron-containing compound may have fluorescence imaging properties. For example, the albumin binder or the boron-containing compound may release fluorescence to visualize cancer (cancer cells and / or cancer tissue).

[0107] According to one embodiment, the albumin binder or the boron-containing compound may have a property of generating reactive oxygen species. For example, the albumin binder or the boron-containing compound may generate reactive oxygen species under light irradiation.

[0108] The carbonyl group of the boron-containing compound represented by Chemical Formula 2 reacts with the amine group of lysine (Lysine-199 or Lys-199) at the SS1 position of albumin to form an imine bond. The nitrogen of the imine bond then combines with the boron of the boron-containing compound to form the albumin conjugate represented by Chemical Formula 1.

[0109] Since the albumin-binding substance includes a group derived from albumin, it can selectively accumulate in cancers (cancer cells and / or cancer tissues) that have albumin receptors. Therefore, the albumin-binding substance can be effectively delivered to cancer cells to target the cancer.

[0110] The albumin-binding compound has a fluorescent chromophore comprising an imine bond and a nitrogen-boron-nitrogen (NBN) group, and thus has fluorescent properties. Therefore, the albumin-binding compound can be used to visualize cancer and / or perform fluorescence imaging.

[0111] Since the albumin conjugate can generate reactive oxygen species when irradiated with light, the albumin conjugate can be used in a photodynamic method to treat cancer.

[0112] Furthermore, since the albumin conjugate can be prepared relatively quickly by simply mixing the boron-containing compound with albumin, the preparation process is very simple. Therefore, since albumin is present in an individual's blood (for example, the content of human serum albumin (HSA) in human blood is about 35 g / L to about 55 g / L), when the boron-containing compound represented by Chemical Formula 2 is administered to an individual, the albumin conjugate represented by Chemical Formula 1 can be relatively quickly and easily generated within the individual.

[0113] Figure 1 The X-ray crystal structure of an albumin conjugate according to one embodiment of the present invention is shown.

[0114] See also Figure 1 The boron-containing compound represented by Chemical Formula 2 covalently bonds to the amine group of the lysine (Lys-199) located at the SS1 site of albumin. Specifically, compared to a binding agent that cannot form when the -SH residue at the cysteine-34 site of albumin is oxidized, the albumin conjugate according to the present invention can be stably formed through the stable binding of the boron-containing compound to albumin. For example, the albumin conjugate according to the present invention is stable within a pH range of approximately 3 to approximately 12, and the SS1 site of albumin is not oxidized even when exposed to air.

[0115] Synthesis Example 1 (Synthesis of Albumin Conjugate)

[0116] In phosphate-buffered saline (PBS) (pH 7.4), the boron-containing compound represented by Chemical Formula 2 and human serum albumin were mixed at a 1:1 ratio to achieve a 200 μM concentration of each, and stirred. This solution was stored in a refrigerator or at room temperature. The albumin conjugate represented by Chemical Formula 1 was prepared according to the following Reaction Formula 1:

[0117] <Reaction Formula 1>

[0118]

[0119] In the reaction formula 1,

[0120] A-NH2 is albumin,

[0121] NH2 is the amine group of lysine located at the SS1 position in albumin.

[0122] A is all groups excluding the amine group of lysine (Lysine-199 or Lys-199) located at the SS1 position in albumin.

[0123] According to Reaction Formula 1, the tricoordinate boron in the boron-containing compound becomes tetracoordinate boron in the albumin conjugate, thereby imparting fluorescent properties to the albumin conjugate. Specifically, the boron-containing compound binds to the amine group of lysine (Lysine-199 or Lys-199) in albumin to form an imine bond, generating a nitrogen-boron-nitrogen (NBN) group, thereby generating a fluorescent chromophore. Specifically, the boron-containing compound represented by Chemical Formula 2 contains a carbonyl group (C=O) at appropriate positions that reacts with the amine group to form an imine bond, and a boronic acid group (-B(OH)2) that reacts with the imine bond to form a tetracoordinate fluorescent chromophore.

[0124] Synthesis Example 2-1 (Synthesis of Boron-Containing Compound B1)

[0125] Compound B1 can be synthesized by methods known in the art, for example, according to the following reaction formula 2-1, but is not limited thereto.

[0126] <Reaction Formula 2-1>

[0127]

[0128] Synthesis Example 2-2 (Synthesis of Boron-Containing Compound B2)

[0129] Compound B2 can be synthesized by methods known in the art, for example, according to the following reaction formula 2-2, but is not limited thereto.

[0130] <Reaction Formula 2-2>

[0131]

[0132] Synthesis Example 2-3 (Synthesis of Boron-Containing Compound B3)

[0133] Compound B3 can be synthesized by methods known in the art, for example, according to the following reaction formula 2-3, but is not limited thereto.

[0134] <Reaction Formula 2-3>

[0135]

[0136] Synthesis Example 2-4 (Synthesis of Boron-Containing Compound B4)

[0137] Compound B4 can be synthesized by methods known in the art, for example, according to the following reaction formula 2-4, but is not limited thereto.

[0138] <Reaction Formula 2-4>

[0139]

[0140] Synthesis Example 2-5 (Synthesis of Boron-Containing Compound B5)

[0141] Compound B5 can be synthesized by methods known in the art, for example, according to the following reaction formula 2-5, but is not limited thereto. In the following reaction formula 2-5, EtOH is ethanol.

[0142] <Reaction Formula 2-5>

[0143]

[0144] Evaluation Example 1 (Combined Ability Assessment)

[0145] In 95% by volume PBS buffer and 5% by volume dimethyl sulfoxide (DMSO), 100 nM boron-containing compound B1 and albumin (HSA) were mixed for 2 hours. The concentration of the albumin was increased, and the change in fluorescence intensity (FI) was measured. Based on this, the dissociation constant (Kd) was calculated, as shown in FIG. Figure 2 shown.

[0146] Figure 2 (a) Shows the change in fluorescence intensity (FI) depending on the concentration ratio of albumin to 100 nM boron-containing compound B1. For example, 0:1 indicates the use of 100 nM albumin (HSA) without a boron-containing compound, 1:0 indicates the use of 100 nM boron-containing compound B1 without albumin (HSA), 1:2 indicates the use of 100 nM boron-containing compound B1 and 200 nM albumin (HSA), and 1:16 indicates the use of 100 nM boron-containing compound B1 and 1600 nM albumin (HSA).

[0147] Figure 2 (b) shows the calculation of the dissociation constant (K) using a fitting program based on the change in the fluorescence intensity (FI) at 530 nm. d ).

[0148] The dissociation constants (K d ) instead of the boron-containing compound B1, and the results are shown in Table 1 below.

[0149] [Table 1]

[0150]

[0151] As can be seen from Table 1, the dissociation constants (K d ) ranged from about 0.1 μM to about 2.5 μM. Thus, it can be seen that albumin binders B-A1 to B-A5, each with a relatively small dissociation constant, exhibited excellent binding capacity. This is likely because boron-containing compounds B1 to B5 not only bind to albumin via van der Waals bonds but also covalently bond to lysine (Lysine-199 or Lys-199) located at the SS1 site of albumin. However, the dissociation constant of the albumin binder according to Chemical Formula 1 is not limited to the range of about 0.1 μM to about 2.5 μM and may be less than or greater than this range.

[0152] On the other hand, the dissociation constant (K) of the boron-containing compound represented by Chemical Formula 2 with lysine as a monomeric amino acid is d ) is approximately several millimolar units, so the boron-containing compound's binding ability to lysine, found in proteins other than albumin, is likely very low. While proteins generally contain a large amount of lysine, the boron-containing compound represented by Chemical Formula 2 has been shown to have very low binding ability to proteins other than albumin. The boron-containing compound represented by Chemical Formula 2 binds particularly strongly to lysine-199 in human serum albumin (HSA). This is due not only to the covalent bond with lysine, but also to the high spatial fit of the overall structure of the compound of Chemical Formula 2 with the SS1 site of HSA. In other words, it is believed that the binding forces generated by van der Waals and hydrogen bonding at the SS1 site, combined with the binding force formed through the covalent bond with lysine, contribute to the strong binding ability of the compound of Chemical Formula 2 to HSA.

[0153] Evaluation Example 2 (Quantum Yield Evaluation)

[0154] The quantum yield (Φ) of each of the albumin binders B-A1 to B-A5 was calculated according to Angew. Chem. Int. ed. 2016, 55, 14728-14732. Specifically, fluorescein, which has a known quantum yield of approximately 79.0% in ethanol solution, was used as a reference sample, and the albumin binders were used as measurement samples. The calculations were performed according to the following formula 1. The results are shown in Table 2.

[0155] <Formula 1>

[0156] Φ = (Φ S ) × (I × Ab S × η 2 ) / (I S × Ab × (η S ) 2 )

[0157] In the formula 1,

[0158] Φ is the quantum yield of the measured sample,

[0159] Φ S is the quantum yield of the reference sample,

[0160] Ab is the absorbance in the absorption spectrum of the measured sample.

[0161] Ab S is the absorbance in the absorption spectrum of the reference sample,

[0162] I is the integration area of ​​the emission spectrum of the measured sample,

[0163] I S is the integrated area of ​​the emission spectrum of the reference sample,

[0164] η is the refractive index of the measured sample,

[0165] η S It is the refractive index of the measured sample.

[0166] [Table 2]

[0167]

[0168] In Table 2, the quantum yield of the boron-containing compound B3 was not detected (ND) due to its relatively low value.

[0169] As can be seen in Table 2, albumin binders B-A1 and B-A5 exhibit excellent fluorescence properties due to their high quantum yields. Therefore, the selective accumulation of albumin binders B-A1 and B-A5 in cancer (cancer cells and / or cancerous tissue) allows for visual confirmation of the location of the cancer. In other words, the albumin binders according to one embodiment of the present invention can be used to perform fluorescent imaging of the cancer location.

[0170] Evaluation Example 3-1 (ROS Generation Evaluation)

[0171] The fluorescence produced by DCFH-DA (2',7'-Dichlorodihydrofluorescein diacetate) is proportional to the amount of reactive oxygen species (ROS) generated.

[0172] In PBS buffer (pH 7.4), 10 μM albumin binder B-A1-HSA and 5 μM DCFH-DA were mixed and irradiated with 530 nm light. The fluorescence generated over time was measured using a scinco FS-2. The results are shown in Figure 2. Figure 3a and Figure 6 As shown. Figure 6 In the equation, “FI-F.I0” means “fluorescence intensity-initial fluorescence intensity”. The albumin-binding compound B-A1-HSA means that in the albumin-binding compound B-A1 prepared by reacting albumin with the boron-containing compound B1, the albumin is human serum albumin (HSA).

[0173] The results of using the albumin binder B-A2-HSA instead of the albumin binder B-A1-HSA are as follows Figure 3b and Figure 6 The albumin conjugate B-A2-HSA means that in the albumin conjugate B-A2 prepared by reacting albumin with the boron-containing compound B2, the albumin is human serum albumin (HSA).

[0174] The results of using the albumin binder B-A3-HSA instead of the albumin binder B-A1-HSA are as follows Figure 3c and Figure 6 The albumin binder B-A3-HSA means that in the albumin binder B-A3 prepared by reacting albumin with the boron-containing compound B3, the albumin is human serum albumin (HSA).

[0175] The results of using the boron-containing compound B1 instead of the albumin binder B-A1-HSA are as follows Figure 4a and Figure 6 shown.

[0176] The results of using the boron-containing compound B2 instead of the albumin binder B-A1-HSA are as follows Figure 4b and Figure 6 shown.

[0177] The results of using the boron-containing compound B3 instead of the albumin binder B-A1-HSA are as follows Figure 4c and Figure 6 shown.

[0178] The results using DCFH-DA instead of the albumin binder B-A1-HSA are as follows Figure 5a and Figure 6 .

[0179] The results using human serum albumin (HSA) instead of DCFH-DA and the albumin conjugate B-A1-HSA are shown in Figure 5b and Figure 6 .

[0180] See the Figures 3a to 3c 、 Figures 4a to 4c 、 Figure 5a and Figure 5bIt can be seen that the albumin conjugate B-A2-HSA according to an embodiment of the present invention generates increased amounts of reactive oxygen species (ROS) compared to using only the boron-containing compound (B1, B2, or B3), only DCFH-DA, or only human serum albumin (HSA). In particular, it can be seen that the albumin conjugate B-A2-HSA exhibits excellent ROS generation when irradiated with light ranging from approximately 520 nm to approximately 540 nm. However, the albumin conjugate according to Chemical Formula 1 exhibits excellent ROS generation capabilities not limited to irradiation with light ranging from approximately 520 nm to approximately 540 nm. The albumin conjugate according to Chemical Formula 1 may also exhibit excellent ROS generation capabilities under irradiation with light of any wavelength, such as ultraviolet light, visible light, near-infrared light, or infrared light.

[0181] See also Figure 6 As shown in Table 2, the albumin conjugate B-A2-HSA has excellent ROS generation ability, but its quantum yield is relatively low.

[0182] Because the albumin conjugate contains tetracoordinate boron, while the boron-containing compound contains tricoordinate boron, the albumin conjugate's ROS-generating capacity is likely superior to that of the boron-containing compound. Specifically, a difference in ROS-generating capacity can be observed between the boron-containing compound and albumin after reaction (or binding) before and after preparation of the albumin conjugate.

[0183] However, see Figure 3c 、 4c and 5b. Since the active oxygen generating ability of the albumin-binding compound B-A3-HSA was relatively similar to that of the boron-containing compound B3 or that of human serum albumin (HSA), the following Evaluation Example 3-2 was performed.

[0184] Evaluation Example 3-2 (Evaluation of ROS Generation Based on Lysine Concentration)

[0185] i) 1.0 mM lysine (hereinafter referred to as Lys) was mixed in PBS buffer (pH 7.4) and irradiated with light at approximately 530 nm. The fluorescence generated over time was measured using a scinco FS-2. The results are shown in the figure. Figure 7a shown.

[0186] ii) 10 μM boron-containing compound B3 was mixed instead of the 1.0 mM lysine (Lys), and the results were as follows Figure 7b As shown, iii) 10 μM boron-containing compound B3 and 0.1 mM lysine (Lys) were mixed instead of the 1.0 mM lysine (Lys), and the results were as follows Figure 7cAs shown, iv) 10 μM boron-containing compound B3 and 1.0 mM lysine (Lys) were mixed instead of the 1.0 mM lysine (Lys), and the results were as follows Figure 7d shown.

[0187] See also Figures 7a to 7d , it can be seen that when the boron-containing compound B3 is mixed with a relatively large concentration of monomeric lysine (e.g., about 1.0 mM), a relatively large amount of reactive oxygen species is generated.

[0188] Since cancer cells and / or cancerous tissues obtain nutrients for growth from albumin, the albumin-binding compound B-A3 can be broken down within cancer cells to produce the boron-containing compound B3. Since cancer cells contain approximately 1.0 mM or more of monomeric lysine and amino acids, the generated boron-containing compound B3 can mix with the monomeric lysine and amino acids, generating a relatively large amount of reactive oxygen species. In other words, the albumin-binding compound B-A3 (or boron-containing compound B3) accumulated in cancer cells is expected to be useful for photodynamic cancer treatment.

[0189] Evaluation Example 4 (Cancer Targeted Evaluation)

[0190] Cancer cells (MDA-MB-231 cells) were transplanted into six mice, and the cancer tissue was confirmed to have grown to approximately 100 mm after about 7 to 10 days. 3 Up to 150 mm 3 Afterwards, i) the vehicle, ii) the albumin conjugate B-A2-BSA (50 μM) prepared by reacting the boron-containing compound B2 with bovine serum albumin (BSA), and iii) the albumin conjugate B-A2-HSA (50 μM) prepared by reacting the boron-containing compound B2 with human serum albumin (HSA), were intravenously injected into mice. Organ tissues of the mice were regularly extracted to observe their fluorescence characteristics. The results are shown in Figure 2. Figure 8 Specifically, the fluorescence characteristics of the heart, lung, liver, kidney, spleen and cancer tissues of mice were observed.

[0191] Nanomaterials can selectively accumulate in cancer tissues through the enhanced permeability and retention (EPR) effect. However, nanomaterials can selectively accumulate in the liver, which may cause side effects such as hepatotoxicity.

[0192] See also Figure 8As can be seen, B-A2-HSA accumulates selectively and efficiently only in cancer tissues, while accumulating relatively little in the liver. This may indicate that B-A2-HSA accumulates in cancer tissues not simply through the EPR effect, but rather selectively due to the ability of cancer tissues to accept albumin. Therefore, B-A2-HSA can reduce the possibility of side effects caused by liver accumulation.

[0193] Evaluation Example 4 was conducted on the boron-containing compound B2. However, since the boron-containing compound represented by Chemical Formula 2 can be prepared into the albumin binder represented by Chemical Formula 1 by the same Reaction Formula 1, it is obvious that the albumin binder of the present invention can selectively accumulate in cancer tissues.

[0194] In addition, the albumin binder represented by Chemical Formula 1 and the boron-containing compound represented by Chemical Formula 2 can selectively accumulate in cancer tissues. Therefore, it is obvious that when an anticancer agent is bound to the albumin binder or the boron-containing compound, the anticancer agent can be effectively and selectively accumulated (or mobilized) in cancer tissues.

[0195] Evaluation Example 5 (Cancer Treatment Evaluation 1)

[0196] Cancer (MDA-MB-231 cells) were transplanted into six mice, and the growth of cancerous tissue to approximately 100 mm was confirmed. 3 or more.

[0197] i) The first subject is the control group.

[0198] ii) injecting the boron-containing compound B2 intravenously (hereinafter referred to as IV) into the second individual. (B2(IV)

[0199] iii) The albumin conjugate B-A2-HSA prepared by reacting the boron-containing compound B2 with human serum albumin (HSA) is intravenously injected into the third subject. (B-A2-HSA(IV))

[0200] iv) Intratumoral injection (IT) of B-A2-HSA into the cancerous tissue of the fourth individual. (B-A2-HSA(IT))

[0201] v) The albumin conjugate B-A2-BSA, prepared by reacting the boron-containing compound B2 with bovine serum albumin (BSA), is intravenously injected into the fifth subject. (B-A2-BSA(IV))

[0202] ⅵ) B-A2-BSA was injected directly into the cancerous tissue of the sixth subject (B-A2-BSA(IT))

[0203] Four hours after the injection, green light (about 490 nm to 530 nm) was used for 20 minutes of irradiation. The injection and green light irradiation were performed once a week for a total of three times. On the 28th day after the transplantation of cancer cells, the size of the cancer tissue of each mouse was compared, and the results were as follows: Figure 9a and Figure 9b shown.

[0204] See also Figure 9a and Figure 9b It was confirmed that the albumin conjugates (B-A2-HSA, B-A2-BSA) according to the present invention can reduce the size of cancer tissue whether injected intravenously or directly into the cancer tissue.

[0205] Since mice do not contain human serum albumin, injection of albumin conjugates (B-A2-HSA, B-A2-BSA) can have a superior cancer treatment effect than injection of boron-containing compound B2. However, it is clear that when human serum albumin is included in an organism other than mice, injection of boron-containing compound B2 can have a superior cancer treatment effect.

[0206] Evaluation Example 6 (Cancer Treatment Evaluation 2)

[0207] Cancer (MDA-MB-231 cells) were transplanted into eight mice, and the growth of the cancer tissue to approximately 100 mm was confirmed. 3 or more.

[0208] i) The first and fifth individuals were the control groups.

[0209] ii) injecting the boron-containing compound B2 intravenously into the second individual and the sixth individual respectively.

[0210] iii) The albumin conjugate B-A2-HSA prepared by reacting the boron-containing compound B2 with human serum albumin (HSA) was intravenously injected into the third and seventh subjects, respectively.

[0211] iv) The albumin conjugate B-A2-BSA prepared by reacting the boron-containing compound B2 with bovine serum albumin (BSA) was intravenously injected into the fourth and eighth subjects respectively.

[0212] Four hours after the intravenous injection, the first to fourth subjects were each irradiated with green light (approximately 490 nm to 530 nm) for 20 minutes, while the fifth to eighth subjects were not irradiated with light. The injection and green light irradiation were performed once a week for a total of three times.

[0213] On the 28th day after the cancer was transplanted, the size of the cancer tissue in each mouse was compared. Figures 10a to 10c shown. Specifically, Figure 10a : is a figure showing the results of staining the cancer of the first to eighth individuals, Figure 10b : is a graph showing the results of extracting cancer from the first to fourth individuals, Figure 10c Graph showing the temporal changes in the size of cancer in the first to fourth subjects.

[0214] See also Figures 10a to 10c It was confirmed that the albumin binders (B-A2-HSA, B-A2-BSA) according to the present invention can effectively reduce the size of cancer tissue under light irradiation.

Claims

1. An albumin binder represented by the following chemical formula 1: <Chemical Formula 1> In the chemical formula 1, A is a group that excludes the amine group in albumin, Z is N, O or C(R 14 ), R 11 to R 14 、R 21 to R 24 and R3 to R6 are each independently selected from hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, formyl, carboxyl, amidino, hydrazine, hydrazide, substituted or unsubstituted C1-C 10 Alkyl, substituted or unsubstituted C2-C 10 Alkenyl, substituted or unsubstituted C2-C 10 Alkynyl, substituted or unsubstituted C1-C 10 Alkoxy, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C1-C 10 Heterocycloalkyl, substituted or unsubstituted C3-C 10 Cycloalkenyl, substituted or unsubstituted C1-C 10 Heterocycloalkenyl, substituted or unsubstituted C6-C 20 Aryl, substituted or unsubstituted C6-C 20 Aryloxy, substituted or unsubstituted C6-C 20 Arylthio, substituted or unsubstituted C1-C 20 heteroaryl, -Si(Q1)(Q2)(Q3), -N(Q1)(Q2), -B(Q1)(Q2), -C(=O)(Q1), -S(=O)2(Q1) and -P(=O)(Q1)(Q2), Optionally, i) R 11 and R 12 ii) R 12 and R 13 iii) R 13 and R 14 iv) R 21 and R 22 ,v)R 22 and R 23 ,ⅵ)R 23 and R 24 or vii) any combination thereof is combined with each other to form a substituted or unsubstituted C3-C 10 Carbocyclic group or substituted or unsubstituted C1-C 10 Heterocyclic groups, m is an integer selected from 1 to 5, Q1 to Q3 are independently selected from hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, amidino, hydrazine, hydrazine; and C1-C3 substituted or unsubstituted by hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, amidino, hydrazine, hydrazine or any combination thereof. 10 Alkyl, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C1-C 10 Alkoxy, C3-C 10 Cycloalkyl, C1-C 10 Heterocycloalkyl, C3-C 10 Cycloalkenyl, C1-C 10 Heterocycloalkenyl, C6-C 20 Aryl and C1-C 20 Heteroaryl.

2. The albumin conjugate according to claim 1, wherein The amine group is an amine group included in lysine.

3. The albumin conjugate according to claim 1, wherein The amine group is located at the SS1 position of the albumin.

4. The albumin conjugate according to claim 1, wherein The albumin binder includes human serum albumin or bovine serum albumin.

5. The albumin binder according to claim 1, wherein in the chemical formula 1, m is 1.

6. The albumin conjugate according to claim 1, wherein The albumin binding body has fluorescent properties.

7. The albumin conjugate according to claim 1, wherein The albumin-bound complex generates reactive oxygen species upon light irradiation.

8. A method for preparing an albumin conjugate, comprising reacting a boron-containing compound represented by the following Chemical Formula 2 with albumin: <Chemical Formula 2> In the chemical formula 2, Z is N, O or C(R 14 ), R 11 to R 14 、R 21 to R 24 and R3 to R6 are each independently selected from hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, formyl, carboxyl, amidino, hydrazine, hydrazide, substituted or unsubstituted C1-C 10 Alkyl, substituted or unsubstituted C2-C 10 Alkenyl, substituted or unsubstituted C2-C 10 Alkynyl, substituted or unsubstituted C1-C 10 Alkoxy, substituted or unsubstituted C3-C 10 Cycloalkyl, substituted or unsubstituted C1-C 10 Heterocycloalkyl, substituted or unsubstituted C3-C 10 Cycloalkenyl, substituted or unsubstituted C1-C 10 Heterocycloalkenyl, substituted or unsubstituted C6-C 20 Aryl, substituted or unsubstituted C6-C 20 Aryloxy, substituted or unsubstituted C6-C 20 Arylthio, substituted or unsubstituted C1-C 20 heteroaryl, -Si(Q1)(Q2)(Q3), -N(Q1)(Q2), -B(Q1)(Q2), -C(=O)(Q1), -S(=O)2(Q1) and -P(=O)(Q1)(Q2), Optionally, i) R 11 and R 12 ii) R 12 and R 13 iii) R 13 and R 14 iv) R 21 and R 22 ,v)R 22 and R 23 ,ⅵ)R 23 and R 24 or vii) any combination thereof is combined with each other to form a substituted or unsubstituted C3-C 10 Carbocyclic group or substituted or unsubstituted C1-C 10 Heterocyclic groups, m is an integer selected from 1 to 5, Q1 to Q3 are independently selected from hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, amidino, hydrazine, hydrazine; and C1-C3 substituted or unsubstituted by hydrogen, deuterium, -F, -Cl, -Br, -I, hydroxyl, cyano, nitro, amidino, hydrazine, hydrazine or any combination thereof. 10 Alkyl, C2-C 10 Alkenyl, C2-C 10 Alkynyl, C1-C 10 Alkoxy, C3-C 10 Cycloalkyl, C1-C 10 Heterocycloalkyl, C3-C 10 Cycloalkenyl, C1-C 10 Heterocycloalkenyl, C6-C 20 Aryl and C1-C 20 Heteroaryl.

9. The preparation method according to claim 8, wherein The step of reacting the boron-containing compound with the albumin is performed outside the body of the individual.

10. The preparation method according to claim 8, wherein The step of reacting the boron-containing compound with albumin is performed in the blood of the individual.

11. A composition for targeting, diagnosing or treating cancer, comprising the albumin binder according to claim 1.

12. A composition for targeting, diagnosing or treating cancer, comprising the boron-containing compound according to claim 8.

13. The composition for targeting, diagnosing or treating cancer according to claim 11, wherein The albumin binding body has fluorescent properties.

14. The composition for targeting, diagnosing or treating cancer according to claim 11, wherein The albumin conjugate has active oxygen generating properties.

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