Endoplasmic reticulum-targeted rhodium (I) complex, preparation method and application thereof

Abstract

The invention discloses an endoplasmic reticulum-targeted rhodium (I) complex, a preparation method and an application thereof. The structural formula of the targeted rhodium (I) complex is shown in Formula I. The preparation method comprises the following steps: Step 1, preparing a ligand: amino isonitrile and chlorambucil are subjected to amidation reaction to obtain a ligand; Step 2, preparing the targeted rhodium (I) complex: the ligand obtained in Step 1 is reacted with phenyl isonitrile rhodium (I) complex to obtain the targeted rhodium (I) complex of Formula I; the targeted rhodium (I) complex is applied to preparing anticancer drugs and preparing type II ICD inducer drugs; the targeted rhodium (I) complex of the invention not only has excellent antitumor activity, but also can be used as a type II ICD inducer to induce ICD in tumor cells; the preparation process is simple, the conditions are mild, and large-scale production is possible, and the industrial and practical application potential is available; the targeted rhodium (I) complex has good biocompatibility and is conducive to clinical use.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to an endoplasmic reticulum-targeted rhodium (I) complex, a preparation method and application thereof. Background Art

[0002] Cancer is the second leading cause of death worldwide. Current treatment strategies such as chemotherapy and radiotherapy are plagued by tumor recurrence and cancer metastasis. Immunotherapy has the advantages of high efficiency, durability, and specificity in killing tumor cells, and has become a promising treatment method after cancer surgery, chemotherapy, and radiotherapy. Immunogenic cell death (ICD) improves the efficacy of tumor treatment by inducing anti-tumor immune responses, and has received widespread attention from the scientific community in recent years. ICD is characterized by the extracellular release of immunostimulatory damage-associated molecular patterns (DAMPs), which can stimulate dendritic cell (DC) maturation and further initiate adaptive anti-tumor immunity by activating T cells. ICD is closely related to endoplasmic reticulum (ER) stress, triggering the unfolded protein response and the release of DAMPs. ICD inducers can be divided into two categories based on their ER targeting ability. Type I ICD inducers induce ICD through non-ER-related molecular targets, such as the clinically used chemical drugs oxaliplatin and doxorubicin; Type II ICD inducers directly target ER to induce ER stress and have higher ICD induction ability, such as some photodynamic / photothermal drugs. However, most ER-targeted photosensitizers or photothermal agents are complex to synthesize and require continuous light irradiation. Therefore, the development of novel type II ICD inducers with ER targeting has potential clinical application prospects.

[0003] Small organic molecules still dominate the FDA-approved drugs (≈75%), but there are few reports of organic molecules for chemotherapy as type II ICD inducers. Metal complexes have unique advantages such as predictable and unique geometric configurations, rich and adjustable redox properties, and diverse ligand exchange kinetics and thermodynamics. They have also been developed as ICD inducers in recent years. For example, anticancer metal drugs based on Pt, Ru, Ir, and Au. Therefore, the rational design of new anticancer metal complexes as type II ICD inducers is expected to become potential drugs for tumor immunotherapy.

[0004] Among the new anticancer metal complexes, rhodium (I) complexes and platinum (II) complexes are isoelectronic and belong to the d 8Rhodium (I) complexes are considered to be a promising non-platinum metal anti-tumor drug because of their planar square electronic configuration. However, there are no reports of rhodium (I) complexes as ICD inducers. In addition, some rhodium (I) complexes cannot exist stably under normal conditions because the electron-rich structure of the rhodium (I) metal center is easily oxidized. Isonitrile ligands have a π-conjugated effect and can stabilize the electron-rich rhodium (I) metal center, making them one of the most commonly reported ligands in rhodium (I) complexes. Benzene isonitrile rhodium (I) complexes are spatially unsaturated due to their planar square structure, and there are intermolecular non-covalent metal interactions. They can self-assemble in the aqueous phase to form nanofibers that exhibit strong near-infrared phosphorescence emission. They are a type of metal complex that has both near-infrared phosphorescence imaging and anti-tumor activity. Summary of the invention

[0005] The purpose of the invention is to provide an endoplasmic reticulum-targeted rhodium (I) complex, a preparation method and an application thereof, so as to solve the problems that traditional type II ICD inducers are relatively few in variety, complex in synthesis and have anti-tumor activity that needs to be improved.

[0006] The present invention is achieved by providing an endoplasmic reticulum-targeted rhodium (I) complex, the structural formula of which is shown in Formula I: Formula I.

[0007] The targeted rhodium (I) complex of the present invention, on the one hand, has excellent anti-tumor activity, and its cytotoxicity to human breast cancer cell MB-231 is better than that of the classic metal anticancer drug cisplatin (CDDP); on the other hand, the rhodium (I) complex of the present invention can target the endoplasmic reticulum, directly induce ROS-dependent ER stress, and show the characteristics of ICD, including exposure of endoplasmic reticulum protein calreticulin (CRT) on the cell surface, secretion of high mobility group protein 1 (HMGB1) and release of adenosine triphosphate (ATP), enhancing tumor immunogenicity and activating the body's anti-tumor immunity. It can be seen that the endoplasmic reticulum-targeted rhodium (I) complex of the present invention not only has excellent anti-tumor activity, but also can act as a type II ICD inducer to induce ICD in tumor cells; therefore, the endoplasmic reticulum-targeted rhodium (I) complex of the present invention can be used for cancer immunotherapy.

[0008] The structural formula of the endoplasmic reticulum-targeted rhodium (I) complex of the present invention is accurate.

[0009] A further technical solution of the present invention is that the anion of the targeted rhodium (I) complex is: Cl – Br – or I – .

[0010] A further technical solution of the present invention is: the targeted rhodium (I) complex is obtained by reacting a ligand with a benzene isonitrile rhodium (I) complex, the targeted rhodium (I) complex can be recorded as [Rh(CN)3L], and the ligand L is 4-(4-(bis(2-chloroethyl)amino)phenyl)-N-(4-(methylimidazolidinyl)phenyl)butyramide.

[0011] The present invention also provides a method for preparing an endoplasmic reticulum-targeted rhodium (I) complex, the preparation method comprising the following steps:

[0012] Step 1, preparing the ligand: subjecting amino isonitrile and chlorambucil to an amidation reaction to obtain a ligand;

[0013] Step 2: preparing a targeted rhodium (I) complex: reacting the ligand obtained in step 1 with a benzyl isocyanate rhodium (I) complex to obtain the targeted rhodium (I) complex of formula I.

[0014] The synthesis of most ER-targeted photosensitizers or photothermal agents is complex and requires continuous light irradiation; the preparation process of the present invention is simple, the conditions are mild, and it is possible to produce on a large scale, and has the potential for industrial and practical applications.

[0015] A further technical solution of the present invention is: the specific steps of step one are:

[0016] 11) Add a cosolvent and chloroform to p-phenylenediamine at room temperature and in an air atmosphere; then add an aqueous potassium hydroxide solution, reflux reaction, extract and collect the organic phase, and treat to obtain aminoisonitrile;

[0017] 12) At room temperature, in an anhydrous and oxygen-free environment, chlorambucil is dissolved in an organic solvent, and then the first catalyst and a polypeptide condensation reagent are added. After the reaction, the amino isonitrile obtained in step 11) and the second catalyst are added to carry out an amidation reaction, and the ligand is obtained after treatment.

[0018] The specific preparation method of the ligand in the present invention uses raw materials and process conditions that are simpler and easier to implement than the prior art, making the preparation method of the ligand simpler, with the possibility of large-scale production, and has the potential for industrial and practical applications.

[0019] A further technical solution of the present invention is: in the step 11), the extraction solvent is dichloromethane, and the co-solvent is ethanol; in the step 12), the organic solvent is dichloromethane, the first catalyst is 4-dimethylaminopyridine (DMAP), the second catalyst is N,N-diisopropylethylamine (DIPEA), and the polypeptide condensation reagent is O-benzotriazole-tetramethyluronium hexafluorophosphate (HBTU).

[0020] A further technical solution of the present invention is that the molar ratio of the aminoisonitrile to chlorambucil is 3:1.

[0021] A further technical solution of the present invention is: the specific steps of step 2 are:

[0022] 21) At room temperature and in an air atmosphere, hydrated rhodium and 2,6-dimethylbenzene isocyanide are dissolved in an organic solvent for reaction to obtain a benzene isocyanide rhodium (I) complex;

[0023] 22) At room temperature and in air atmosphere, the ligand obtained in step 1 and the benzyl isocyanate rhodium (I) complex are dissolved in an organic solvent for reaction, and recrystallized to obtain the targeted rhodium (I) complex of formula I.

[0024] A further technical solution of the present invention is: the organic solvent in step 21) is dichloromethane, and the molar ratio of hydrated rhodium to 2,6-dimethylbenzene isocyanate is 1:6; the organic solvent in step 22) is dichloromethane, and the molar ratio of the ligand to the benzene isocyanate rhodium (I) complex is 1:1.05.

[0025] The present invention also provides an application of an endoplasmic reticulum-targeted rhodium (I) complex. The targeted rhodium (I) complex is obtained by the preparation method and is applied to the preparation of anticancer drugs and type II ICD inducer drugs.

[0026] The endoplasmic reticulum-targeted rhodium (I) complex used in the present invention has good biocompatibility and is conducive to clinical use.

[0027] Beneficial effects of the present invention: The targeted rhodium (I) complex of the present invention, on the one hand, has excellent anti-tumor activity, and its cytotoxicity to human breast cancer cells MB-231 is better than that of the classic metal anticancer drug cisplatin (CDDP); on the other hand, the rhodium (I) complex of the present invention can target the endoplasmic reticulum, directly induce ROS-dependent ER stress, and show the characteristics of ICD, including exposure of the endoplasmic reticulum protein calreticulin (CRT) on the cell surface, secretion of high mobility group protein 1 (HMGB1) and release of adenosine triphosphate (ATP), enhancing tumor immunogenicity and activating the body's anti-tumor immunity. It can be seen that the endoplasmic reticulum-targeted rhodium (I) complex of the present invention not only has excellent anti-tumor activity, but also can act as a type II ICD inducer to induce ICD in tumor cells; therefore, the endoplasmic reticulum-targeted rhodium (I) complex of the present invention can be used for cancer immunotherapy; the structural formula of the endoplasmic reticulum-targeted rhodium (I) complex of the present invention is accurate.

[0028] The synthesis of most ER-targeted photosensitizers or photothermal agents is complex and requires continuous light irradiation; the preparation process of the present invention is simple, the conditions are mild, and it is possible to mass produce, and it has the potential for industrial and practical applications. The specific preparation method of the ligand in the present invention, the raw materials used and the process conditions are simpler and easier to implement than the prior art, making the preparation method of the ligand simpler, and it is possible to mass produce, and it has the potential for industrial and practical applications.

[0029] The endoplasmic reticulum-targeted rhodium (I) complex used in the present invention has good biocompatibility and is conducive to clinical use. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 The ligand prepared in Example 1 of the present invention 1 H-NMR spectrum (CH3Cl3-d 6 , 400MHz);

[0031] Figure 2 The targeted rhodium (I) complex prepared in Example 1 of the present invention 1 H-NMR spectrum (CH3Cl3-d 6 , 400MHz);

[0032] Figure 3 The preparation method of the targeted rhodium (I) complex, ligand and benzene isonitrile rhodium (I) complex according to Example 1 of the present invention is as follows: 1 H-NMR spectrum comparison chart (CH3Cl3-d 6 , 101MHz);

[0033] Figure 4 The targeted rhodium (I) complex prepared in Example 1 of the present invention 13 C-NMR spectrum (CH3Cl3-d 6 , 101MHz);

[0034] Figure 5 The cytotoxicity of the targeted rhodium (I) complex prepared in Example 1 of the present invention and CDDP to human breast cancer cells MB-231, human liver cancer cells 7404 and human cervical cancer cells Hela;

[0035] Figure 6 This is a fluorescence microscope image of ROS generation in MB-231 cells by the targeted rhodium (I) complex and CDDP prepared in Example 1 of the present invention (scale bar is 50 μm);

[0036] Figure 7 is a fluorescence microscope image of the CRT protein expression of MB-231 cells after the targeted rhodium (I) complex prepared in Example 1 and CDDP treatment (scale bar is 50 μm);

[0037] Figure 8 is a fluorescence microscope image of HMGB1 protein expression of MB-231 cells after the targeted rhodium (I) complex prepared in Example 1 and CDDP treatment (scale bar is 50 μm);

[0038] Fig. 9 It is the ATP content in MB-231 cells after the targeted rhodium (I) complex prepared in Example 1 and CDDP treatment. DETAILED DESCRIPTION

[0039] The following describes the embodiments of the present invention through specific examples, and those skilled in the art can easily understand other advantages and effects of the present invention from the contents disclosed in this specification. The present invention can also be implemented or applied through other different specific embodiments, and the details in this specification can also be modified or changed in various ways based on different viewpoints and applications without departing from the spirit of the present invention.

[0040] It should be noted that the structures, proportions, sizes, etc. illustrated in the drawings of this specification are only used to match the contents disclosed in the specification for people familiar with this technology to understand and read, and are not used to limit the limiting conditions for the implementation of the present invention, so they have no substantial technical significance. Any modification of the structure, change of the proportion relationship or adjustment of the size should still fall within the scope of the technical content disclosed by the present invention without affecting the effects and purposes that can be achieved by the present invention. At the same time, the terms such as "upper", "lower", "left", "right", "middle" and "one" quoted in this specification are only for the convenience of description, and are not used to limit the scope of the implementation of the present invention. The change or adjustment of their relative relationship should also be regarded as the scope of the implementation of the present invention without substantially changing the technical content. Example 1

[0041] 1. Preparation of ligands, comprising the following steps:

[0042] (1) Synthesis of amino isonitrile:

[0043] Weighed p-phenylenediamine (6.0 g, 55.5 mmol) was added to a 500 mL round-bottom flask, and then co-solvent ethanol (25 mL) was added, and then chloroform (80 mL) was added to fully dissolve; then weighed potassium hydroxide (40 g, 713.17 mmol) was dissolved in ultrapure water (140 mL) on an ice bath; the potassium hydroxide aqueous solution was added to the round-bottom flask with a dropper and refluxed for 2 hours. After treatment, the organic phase was extracted with dichloromethane, and then dried over anhydrous magnesium sulfate (dark reddish brown), filtered, and spin-dried to obtain a solid. The product was purified by column chromatography and vacuum dried to obtain aminoisocyanate (2.3 g, 19.5 mmol).

[0044] (2) Ligand synthesis:

[0045] A magnetic stirrer was placed in a 50 mL round-bottom flask, and dichloromethane (10 mL) was added, followed by the weighed chlorambucil (304.21 mg, 1 mmol); then the catalyst DIPEA (309 μL, 5.01 mmol) and the peptide coupling reagent HBTU (244 mg, 900 μmol) were added, and the reaction was stirred for 5 minutes; then the weighed aminoisocyanate (354 mg, 3mmol) and the catalyst DMAP (3.22 mg, 40 μmol) were added, and the resulting mixture was stirred at room temperature for 5 hours; then filtered and concentrated to about 2 mL to collect the crude product. The crude product was purified by column chromatography and vacuum dried to obtain the ligand, the ligand 1 H-NMR spectrum (CH3Cl3-d 6 , 400MHz) Figure 1 shown.

[0046] 2. Preparation of the complex, comprising the following steps:

[0047] (1) Synthesis of Benzene Isonitrile Rhodium (I) Complex:

[0048] The weighed [Rh(COD)Cl]2 (100 mg, 0.203 mmol) was added to dichloromethane (10 mL), stirred for 5-10 minutes, and fully dissolved; then the weighed 2,6-dimethylbenzene isocyanate (159.61 mg, 1.22 mmol) was dissolved in dichloromethane (5 mL), rinsed twice, loaded into a 10 mL constant pressure dropping funnel, and slowly added dropwise to [Rh(COD)Cl]2, and reacted at room temperature for 30 minutes; subsequently, the reaction solution was concentrated by rotary evaporation, 50 mL of n-hexane was added, a brown precipitate was precipitated, and it was placed in a refrigerator and allowed to stand for 3 hours; finally, it was collected by filtration, and washed several times with n-hexane and ether to obtain the precursor benzene isocyanate rhodium (I) complex.

[0049] (2) Complex synthesis:

[0050] The precursor benzene isonitrile rhodium (I) complex (70.7 mg, 0.132 mmol) was weighed into a 150 mL round-bottom flask and stirred for 5-10 minutes to fully dissolve; the weighed ligand (40.0 mg, 0.0987 mmol) was added into a 5 mL centrifuge tube, and then dichloromethane (3 mL) was added for ultrasonic dissolution, and the mixture was transferred to a constant pressure dropping funnel with a Pasteur pipette, and washed twice with dichloromethane, and reacted at room temperature for 30 minutes; then the reaction solution was concentrated by rotary evaporation, n-hexane was added, a precipitate was precipitated, and placed in a refrigerator for 3 hours; finally, the mixture was filtered and collected, and washed 3 times with n-hexane and ether to obtain a crude product; the crude product was purified by column chromatography and vacuum dried to obtain a targeted rhodium (I) complex (30 mg, 0.0332 mmol), and the targeted rhodium (I) complex 1 H-NMR spectrum (CH3Cl3-d 6 , 400MHz) Figure 2 As shown, the targeted rhodium (I) complex 13 C-NMR spectrum (CH3Cl3-d 6 , 101MHz) Figure 4 shown.

[0051] Targeted rhodium(I) complexes, ligands and preparation of benzyl isonitrile rhodium(I) complexes 1 H-NMR spectrum comparison chart (CH3Cl3-d 6 , 101MHz) Figure 3 shown.

[0052] The reaction equation of a method for preparing an endoplasmic reticulum-targeted rhodium (I) complex is as follows:

[0053] . Example 2

[0054] In vitro antitumor activity study of targeted rhodium(I) complexes

[0055] Antitumor activity test (MTT method): The antitumor ability of targeted rhodium (I) complexes is mainly determined by the MTT method, and CDDP is used as a drug control. The MTT method is a classic method for determining the antitumor activity of drugs. The operating steps are as follows:

[0056] MB-231, 7404 and Hela cells growing in logarithmic phase were seeded in 96-well plates at a density of 8000 per well. After culturing in a CO2 incubator for 24 hours, a series of different concentrations of the targeted rhodium (I) complex prepared in Example 1 and CDDP diluted with culture medium were added, and then incubated in the incubator for 24 hours, MTT was added, and the culture medium was removed after 4 hours, and DMSO was added. After shaking, the OD value at 490 nm was measured.

[0057] like Figure 5 As shown in the experimental results, it can be seen that the targeted rhodium (I) complex has excellent anti-tumor activity and a certain degree of selectivity. The targeted rhodium (I) complex has an excellent anti-tumor activity against the human breast cancer cell line MB-231 (IC 50 :8 .727 μM), human hepatoma cell line 7404 (IC 50 :22.91 μM) were superior to CDDP (IC 50 18.02-28.57 μM), and its cytotoxicity to the human breast cancer cell line MB-231 was significantly greater than that of CDDP; its cytotoxicity to the human cervical cancer cell line Hela (IC 50 :39.78 μM) is slightly lower than CDDP (IC 50 :31.87 μM). In view of the good antitumor activity of the targeted rhodium (I) complex on MB-231 cells, MB-231 was selected for subsequent cell experiments. Example 3

[0058] In vivo reactive oxygen species detection

[0059] In order to verify whether the targeted rhodium (I) complex can induce ROS-dependent ER stress, 2',7'-dichlorofluorescein diacetate (DCFH-DA) was selected as an indicator to detect the ability of the targeted rhodium (I) complex to produce ROS in MB-231 cells. 5 Cells were inoculated on 24-well plates and incubated overnight. Then, the cells were treated with 5 μg / mL PBS, targeted rhodium (I) complexes, and CDDP for 12 hours. DCFH-DA was diluted with serum-free culture medium at a ratio of 1:1000 to a final concentration of 10 μmol / L. The original cell culture medium was removed and 200 μL of the diluted DCFH-DA was added. Incubated in a 37°C cell culture incubator for 20 min. The cells were then washed three times with serum-free cell culture medium to fully remove DCFH-DA that did not enter the cells. DAPI staining was then used to locate the cell nucleus for 5 min. Finally, the cells were washed three times with PBS and observed under an inverted fluorescence microscope to obtain fluorescence data.

[0060] The experimental results are as follows Figure 6 As shown, the reactive oxygen species in the cells can oxidize the non-fluorescent DCFH to generate green fluorescent DCF. The cells treated with the targeted rhodium (I) complex will emit bright green fluorescence, while those treated with CDDP will have no obvious fluorescence, which proves the excellent ROS generation effect of the targeted rhodium (I) complex, indicating that the targeted rhodium (I) complex can cause ROS-dependent ER stress. Example 4

[0061] ICD marker testing

[0062] (1) Observation of cell CRT exposure using fluorescence microscopy

[0063] MB-231 cells in the logarithmic growth phase were inoculated on a 24-well plate dedicated cell slide, with 1.0 x10 5 cells and cultured for 24 h. The cells were treated with PBS, CDDP and targeted rhodium (I) complexes and incubated for 6 h. After the administration, the cells were treated with ice methanol and 0.1% Triton X-100 for 5 min, respectively. After each operation, the cells were washed 3 times with ice PBS. Then, they were blocked with 1% BSA for 1 h and incubated with primary antibodies overnight at 4 °C. They were washed three times with PBST and incubated with goat anti-rabbit IgG H&L (Alexa Fluor® 488) secondary antibodies for 2 h at room temperature. Finally, the cell nuclei were stained with DAPI, and the cell surface was placed on a slide for sealing and observed with a fluorescent inverted microscope.

[0064] When tumor cells undergo ICD, CRT is exposed on the cell membrane surface. Figure 7 As shown, the cell surface treated with the targeted rhodium (I) complex showed obvious green fluorescence, indicating that CRT was gradually exposed on the cell membrane. However, there was no obvious green fluorescence on the cell surface treated with CDDP, and CRT was almost not induced to translocate to the cell surface, indicating that cell death induced by CDDP alone was immunologically silent.

[0065] (2) Observation of cell HMGB1 release by fluorescence microscopy

[0066] MB-231 cells in the logarithmic growth phase were inoculated on a 24-well plate dedicated cell slide, with 1.0x10 5cells and cultured for 24 h. The cells were treated with PBS, CDDP and targeted rhodium (I) complexes and incubated for 12 h. After the administration, the cells were treated with ice methanol and 0.1% TritonX-100 for 5 min, respectively. After each operation, the cells were washed 3 times with ice PBS. Then, they were blocked with 1% BSA for 1 h and incubated with primary antibodies overnight at 4°C. They were washed three times with PBST and incubated with goat anti-rabbit IgG H&L (Alexa Fluor® 488) secondary antibodies for 2 h at room temperature. Finally, the cell nuclei were stained with DAPI, and the cells were mounted on a slide for sealing and observed with a fluorescent inverted microscope.

[0067] Immunofluorescence analysis Figure 8 As shown, the blue fluorescence of the cell nucleus in the cells treated with the targeted rhodium (I) complex overlapped less with the green fluorescence of HMGB1 than that in the PBS group and the CDDP group, confirming the release of HMGB1 from tumor cells.

[0068] (3) ATP efflux

[0069] The cell administration method is the same as that for detecting HMGB1. Then, the culture medium is removed, and 100 μL of lysis solution is added to each well to lyse the cells. Then, centrifuge at 4°C, 12,000 g for 5 min, take the supernatant, and perform subsequent determination according to the steps of the ATP detection kit.

[0070] The results of ATP concentration in MB231 cells are as follows Fig. 9 As shown, the concentration of ATP in cells treated with the targeted rhodium (I) complex was significantly lower than that in the PBS group and the CDDP group, confirming the efflux of ATP.

[0071] In summary, the results of CRT exposure, HMGB1 release, and ATP secretion all confirm that the targeted, rhodium(I) complex can induce ICD, thereby stimulating systemic immune responses and improving antitumor effects.

[0072] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. An endoplasmic reticulum-targeted rhodium (I) complex, characterized in that The structural formula of the targeted rhodium (I) complex is shown in Formula I:

2. A method for preparing an endoplasmic reticulum-targeted rhodium (I) complex, characterized in that: The preparation method comprises the following steps: Step 1, preparing the ligand: subjecting amino isonitrile and chlorambucil to an amidation reaction to obtain a ligand; The structural formula of the amino isonitrile is: Step 2, preparing a targeted rhodium (I) complex: reacting the ligand obtained in step 1 with a benzyl isocyanate rhodium (I) complex to obtain the targeted rhodium (I) complex of formula I described in claim 1.

3. A method for preparing an endoplasmic reticulum-targeted rhodium (I) complex according to claim 2, characterized in that: The specific steps of step one are: 11) adding a cosolvent and chloroform to p-phenylenediamine at room temperature and in an air atmosphere; then adding an aqueous potassium hydroxide solution, reflux reaction, extracting and collecting the organic phase, and treating to obtain aminoisonitrile; 12) At room temperature, in an anhydrous and oxygen-free environment, chlorambucil is dissolved in an organic solvent, and then the first catalyst and a polypeptide condensation reagent are added. After the reaction, the amino isonitrile obtained in step 11) and the second catalyst are added to carry out an amidation reaction, and the ligand is obtained after treatment.

4. A method for preparing an endoplasmic reticulum-targeted rhodium (I) complex according to claim 3, characterized in that: In step 11), the extraction solvent is dichloromethane and the co-solvent is ethanol; in step 12), the organic solvent is dichloromethane, the first catalyst is 4-dimethylaminopyridine, the second catalyst is N,N-diisopropylethylamine, and the polypeptide condensation reagent is O-benzotriazole-tetramethyluronium hexafluorophosphate.

5. A method for preparing an endoplasmic reticulum-targeted rhodium (I) complex according to claim 2, characterized in that: The molar ratio of the amino isonitrile to chlorambucil is 3:

1.

6. A method for preparing an endoplasmic reticulum-targeted rhodium (I) complex according to claim 2, characterized in that: The specific steps of step 2 are: 21) at room temperature and in an air atmosphere, dissolving hydrated rhodium and 2,6-dimethylbenzene isocyanide in an organic solvent for reaction to obtain a benzene isocyanide rhodium (I) complex; 22) At room temperature and in an air atmosphere, the ligand obtained in step 1 and the benzyl isocyanate rhodium (I) complex are dissolved in an organic solvent for reaction, and recrystallized to obtain the targeted rhodium (I) complex of formula I.

7. A method for preparing an endoplasmic reticulum-targeted rhodium (I) complex according to claim 6, characterized in that: The organic solvent in step 21) is dichloromethane, and the molar ratio of hydrated rhodium to 2,6-dimethylbenzene isocyanate is 1:

6. The organic solvent in step 22) is dichloromethane, and the molar ratio of the ligand to the benzene isocyanate rhodium (I) complex is 1:1.

05.

8. An application of an endoplasmic reticulum-targeted rhodium (I) complex, characterized in that: The targeted rhodium (I) complex is obtained by the preparation method described in any one of claims 2 to 7, and is used for preparing anticancer drugs and type II ICD inducer drugs.

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