Iridium-doped copolymer, nanomedicine and preparation method and application thereof

Abstract

The present application relates to a kind of iridium doped copolymer, nano drug and its preparation method and application, the iridium doped copolymer is a kind of block copolymer, by ring metal iridium complex monomer, conjugated double bromine monomer and double tin monomer polymerization is obtained;The ring metal iridium complex monomer contains the double bromine functional group that can participate in polymerization reaction;The double tin monomer contains two trimethyl tin groups.This iridium doped copolymer has photothermal or acoustic dynamic effect, temperature is rapidly increased under light, or under ultrasound, active oxygen is generated.The amphiphilic polymer is used to coat the iridium doped copolymer to prepare into nanoparticle, with the increase of iridium doped content, the targeting of the nanoparticle can be regulated, and better treatment effect is realized.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of biochemical technology, and in particular to an iridium-doped copolymer capable of regulating organelle targeting, a nanodrug, and a preparation method and application thereof. BACKGROUND

[0002] Various organelles in cells, such as mitochondria, endoplasmic reticulum, and nucleus, are involved in numerous biochemical processes, mediate intracellular signal transduction, and play a decisive role in cell fate. In recent years, targeting important organelles through nanodelivery has become a research hotspot. By coupling reactions, targeting groups can be connected to nanocarriers, which can endow nanodrugs with organelle targeting. This precise delivery not only can increase the local concentration of drugs at the target organelle, enhance the therapeutic effect, but also can reduce the toxic side effects caused by the interaction of drugs with non-target organelles, which is of great significance to chemotherapy, gene therapy, photodynamic therapy, and other treatment methods.

[0003] Currently, organelle targeting groups can be divided into two categories: chemical small molecules and biological macromolecules. Chemical small molecule targeting groups, such as the mitochondrial targeting group triphenylphosphine and the endoplasmic reticulum targeting group p-toluenesulfonamide, have the advantages of small size and easy modification to nanocarriers, but also have the defects of limited types and quantities, low targeting efficiency, and high systemic toxicity. As for polypeptides, proteins, nucleic acids, and other biological macromolecule targeting groups, they have good targeting but have problems such as easy degradation and easy induction of immunogenic response. Moreover, neither chemical small molecules nor biological macromolecule targeting groups can be randomly regulated in targeting, and when the targeting needs to be changed, the targeting group and the corresponding synthesis method need to be changed, resulting in complicated synthesis and high cost. Therefore, there is an urgent need to develop a new targeting system that is efficient, stable, and can be randomly regulated in targeting.

[0004] Iridium complexes have excellent photo-physical and photo-chemical properties, low toxicity and side effects, and can be regulated in organelle targeting by regulating ligands, which is a new type of metal drug with great potential. Currently, there have been many reports on the influence of iridium complex doping on the photo-physical properties, electrochemical properties, and photo-thermal conversion efficiency of conjugated polymers, but there is still no research on the influence of iridium doping on the organelle targeting of polymers. It is reasonably speculated that the excellent biological activity of iridium complexes will affect the organelle targeting of the doped polymers, and the organelle targeting can be controlled by regulating the doping content. However, although iridium complexes have potential, their use in this regard has not been fully explored, which highlights a major gap in the current research on organelle-targeting nanodrugs. SUMMARY

[0005] The present application aims to provide an iridium-doped copolymer with controllable organelle targeting, a nanodrug, and a preparation method and application thereof. The iridium-doped copolymer is a block copolymer. The iridium-doped copolymer is coated with an amphiphilic polymer to prepare nanoparticles. With the increase of the content of iridium doping, the nanoparticles can target different organelles to achieve better therapeutic effect.

[0006] To this end, in a first aspect, the present application provides an iridium-doped copolymer, which is obtained by polymerization of a cyclometalated iridium complex monomer, a conjugated dibromine monomer, and a bis-stannane monomer.

[0007] The cyclometalated iridium complex monomer has a double bromine functional group that can participate in the polymerization reaction.

[0008] The bis-stannane monomer contains two trimethyltin groups.

[0009] Specifically, the cyclometalated iridium complex monomer is a compound containing two -Br, i.e., the cyclometalated iridium complex monomer contains two C^N ligands and one N^N ligand, wherein the N^N ligand contains two -Br. The conjugated dibromine monomer is a compound containing two -Br and having a conjugated structure.

[0010] In a specific embodiment, the iridium-doped copolymer is obtained by polymerization of one cyclometalated iridium complex monomer, one conjugated dibromine monomer, and one bis-stannane monomer.

[0011] In another specific embodiment, the iridium-doped copolymer is obtained by polymerization of one cyclometalated iridium complex monomer, two conjugated dibromine monomers, and one bis-stannane monomer.

[0012] Further, the iridium-doped copolymer is a block copolymer.

[0013] Further, the ratio of the sum of the moles of the cyclometalated iridium complex monomer and the conjugated dibromine monomer to the mole of the bis-stannane monomer is 1-1.2:1-1.2, including but not limited to 1:1, 1:1.1, 1:1.2, 1.1:1, 1.2:1, etc., and preferably 1:1.

[0014] Further, the general formula of the cyclometalated iridium complex monomer is wherein the ligand includes at least one of

[0015] The C^N (i.e., C︶N in the structural formula) ligand includes at least one of

[0016] ​​

[0017] Further, the cyclometalated iridium monomer comprises at least one of the following compounds:

[0018]

[0019] Further, the conjugated dibromide monomer is selected from one or more of the following compounds,

[0020]

[0021]

[0022] Further, the bis-stannane monomer comprises one or more of the following compounds,

[0023]

[0024]

[0025] Further, the iridium-doped copolymer comprises at least one of the following:

[0026]

[0027] wherein x, y, z each ranges from 0 to 10, and is not 0, and r represents random copolymerization.

[0028] In a second aspect of the present application, a preparation method of the iridium-doped copolymer of the first aspect is provided, comprising polymerizing the cyclometalated iridium complex monomer, the conjugated dibromide monomer, and the bis-stannane monomer in an organic solvent; the organic solvent preferably comprises anhydrous toluene.

[0029] In a third aspect of the present application, the iridium-doped copolymer is provided for use in the preparation of a nano-drug.

[0030] In a fourth aspect of the present application, a nano-drug is provided, comprising: a) an amphiphilic polymer; and b) the iridium-doped copolymer of the present application.

[0031] The nano-drug of the present application uses an amphiphilic polymer to coat the iridium-doped copolymer of the present application to form nanoparticles, which are accumulated in tumor sites through intravenous injection and blood circulation, and then enter tumor cells. Depending on the content of the iridium dopant, the nanoparticles target different organelles. Irradiation with infrared light in the second region generates heat, or ultrasonic irradiation generates reactive oxygen species to kill tumor cells.

[0032] In specific embodiments, the amphiphilic polymer can comprise at least one of PLGA-PEG, DSPE-PEG, or PEG-b-PPG-b-PEG; and the organelle targeting of the nano-drug can be regulated by adjusting the content of the iridium dopant in the iridium-doped copolymer.

[0033] In the research process, the application provides a method for regulating organelle targeting, which can regulate the organelle targeting of controllable nanoparticles by doping iridium. A plurality of cyclometalated iridium monomers are synthesized, and the cyclometalated iridium monomers can undergo stille coupling reaction with conjugated dibromide monomers and double-tin-containing monomers in the presence of a catalyst. The iridium-doped copolymer provided by the application can be co-assembled with an amphiphilic polymer to form nanoparticles. By regulating the doping content, the organelle targeting of the nanoparticles can be changed, for example, with the increase of the iridium doping content, the nanoparticles are changed from non-targeting to mitochondrion targeting and then to endoplasmic reticulum targeting. The iridium-doped copolymer provided by the application can be used as a drug carrier to realize the function of subcellular organelle targeted drug delivery. For example, by adjusting the iridium content, the nanoparticles can be targeted to mitochondria, and when the copolymer carrier of the application carries drugs into cells, the drugs can be efficiently delivered to mitochondria, thereby reducing off-target effects and enhancing efficacy.

[0034] Compared with the prior art, the technical scheme of the application has the following advantages:

[0035] (1) The method for regulating organelle targeting provided by the application can dope iridium in the polymer main chain by simple one-pot cooking, and the doping iridium content can be controllably regulated by adjusting the feeding ratio, so as to regulate the organelle targeting of the nanoparticles assembled by the polymer; no traditional targeting group is needed, and the targeting of various organelles can be realized by a simple and controllable method.

[0036] (2) The degradable copolymer provided by the application has photothermal / photodynamic / sonodynamic effect. The iridium-doped copolymer has strong absorption in the range of 600-1200 nm, and it can generate heat or active oxygen under laser or ultrasonic irradiation, thereby realizing photothermal / photodynamic / sonodynamic therapy.

[0037] (3) The degradable copolymer provided by the application can be coated and self-assembled into nanoparticles by an amphiphilic carrier to improve the stability of the drug.

[0038] (4) The application provides a corresponding preparation method, and the process flow is simple and the product stability is high. BRIEF DESCRIPTION OF DRAWINGS

[0039] Various other advantages and benefits will become apparent to those of ordinary skill in the art upon reading the following detailed description of the preferred embodiments. The accompanying drawings are merely intended to illustrate the preferred embodiments and are not to be considered as limiting the application thereto. In the drawings:

[0040] Figure 1 is a particle size diagram of the nanoparticles;

[0041] Figure 2 is a UV absorption spectrum diagram of the nanoparticles loaded with the degradable copolymer;

[0042] Figure 3 Photothermal change graph of nanoparticles encapsulating degradable copolymer;

[0043] Figures 4-1 to 4-3 The figure is the colocalization coefficient graph of nanoparticles with different iridium doping contents and mitochondria, lysosomes and endoplasmic reticulum, respectively;

[0044] Figure 4-4 The figure is the relative content statistical graph of nanoparticles with different iridium doping contents in the above three organelles. DETAILED DESCRIPTION

[0045] Exemplary embodiments of the present disclosure will be described in greater detail below with reference to the accompanying drawings. While exemplary embodiments of the present disclosure are shown in the drawings, it is understood that the present disclosure can be embodied in various forms without being limited by the embodiments set forth herein. Rather, these embodiments are provided so that the present disclosure can be more thoroughly understood, and so that the scope of the present disclosure can be completely conveyed to those skilled in the art.

[0046] Example 1 Monomer 1

[0047]

[0048] Dichlorotetrakis[2-(2-pyridyl)phenyl]diiridium(III) (118 mg, 0.11 mmol) and 4-bromo-2-(4-bromopyridin-2-yl)pyridine (69.1 mg, 0.22 mmol) were dissolved in a mixture of MeOH and DCM (1:1, 10 mL) and heated at 55°C under N2atmosphere for 24 hours, then the solution was cooled and an aqueous solution of ammonium hexafluorophosphate was added dropwise. The solvent was removed under reduced pressure. Column chromatography was performed on silica gel using a gradient of DCM and MeOH (DCM / MeOH = 19:1) to purify the crude product. The fractions containing the product were collected and the solvent was removed under reduced pressure to obtain Monomer 1. 1 H NMR (400 MHz, DMSO-d6) δ 9.33 (d, 2H), 8.26 (d, 2H), 8.04-7.85 (m, 6H), 7.74 (dd, 2H), 7.65 (d, 2H), 7.16 (ddd, 2H), 7.01 (td, 2H), 6.89 (td, 2H), 6.14 (dd, 2H).

[0049] Example 2 Monomer 2

[0050]

[0051] Dichlorotetrakis[2-(2-pyridyl)phenyl]diiridium(III) (118 mg, 0.11 mmol) and 5,5'-dibromo-2,2'-bipyridine (69.1 mg, 0.22 mmol) were dissolved in a mixture of MeOH and DCM (1 : 1, 10 mL) and heated at 55 °C under N2atmosphere for 24 h, then the solution was cooled and an aqueous solution of ammonium hexafluorophosphate was added dropwise. The solvent was removed under reduced pressure. Column chromatography on silica gel using a gradient of DCM and MeOH (DCM / MeOH = 19: 1) was performed to purify the crude product. Fractions containing the product were collected and the solvent was removed under reduced pressure to give monomer 2. 1 H NMR (400 MHz, CD3CN) δ 8.40 (d, 2H), 8.29 (dd, 2H), 8.07 (d), 7.91 (d, 2H), 7.87 (m, 2H), 7.82 (dd, 2H), 7.65 (m, 2H), 7.09-7.04 (m, 4H), 6.94 (td, 2H), 6.25 (dd, 2H).

[0052] Example 3 Monomer 3

[0053]

[0054] Dichlorotetrakis[2-(2-pyridyl)phenyl]diiridium(III) (118 mg, 0.11 mmol) and 4,7-dibromophenanthroline (74.4 mg, 0.22 mmol) were dissolved in a mixture of MeOH and DCM (1 : 1, 10 mL) and heated at 55 °C under N2atmosphere for 24 h, then the solution was cooled and an aqueous solution of ammonium hexafluorophosphate was added dropwise. The solvent was removed under reduced pressure. Column chromatography on silica gel using a gradient of DCM and MeOH (DCM / MeOH = 19: 1) was performed to purify the crude product. Fractions containing the product were collected and the solvent was removed under reduced pressure to give monomer 3.

[0055] Example 4 Monomer 4

[0056]

[0057] Dichlorotetrakis[2-(2-pyridyl)phenyl]diiridium(III) (118 mg, 0.11 mmol) and 3,8-dibromo-phenanthroline (74.4 mg, 0.22 mmol) were dissolved in a mixture of MeOH and DCM (1 : 1, 10 mL) and heated at 55 °C under N2atmosphere for 24 h, then the solution was cooled and an aqueous solution of ammonium hexafluorophosphate was added dropwise. The solvent was removed under reduced pressure. Column chromatography on silica gel using a gradient of DCM and MeOH (DCM / MeOH = 19: 1) was performed to purify the crude product. Fractions containing the product were collected and the solvent was removed under reduced pressure to give monomer 4. 1H NMR (400 MHz, DMSO-d6) δ 9.19 (d, 2H), 8.67 (s, 2H), 8.16 (d, 2H), 7.96 (d, 2H), 7.79 (t, 2H), 7.73 (d, 2H), 7.35 (d, 2H), 7.09 (t, 2H), 6.99 (q, 4H), 6.34 (d, 2H).

[0058] Example 5 Monomer 5

[0059]

[0060] Dichlorotetrakis[2-(2-pyridyl)phenyl]diiridium(III) (118 mg, 0.11 mmol) and 4,7-bis(4-bromophenyl)-1,10-phenanthroline (108 mg, 0.22 mmol) were dissolved in a mixture of MeOH and DCM (1 :1, 10 mL) and heated at 55 °C under N2atmosphere for 24 h, then the solution was cooled and an aqueous solution of ammonium hexafluorophosphate was added dropwise. The solvent was removed under reduced pressure. Column chromatography was performed on silica gel using a gradient of DCM and MeOH (DCM / MeOH = 19:1 ) to purify the crude product. The fractions containing the product were collected and the solvent was removed under reduced pressure to give monomer 5.

[0061] Example 6 Formula I copolymer

[0062]

[0063] The double tin monomer shown in formula 24 (106.1 mg, 0.12 mmol), double bromine monomer shown in formula 8 (40.2 mg, 0.11 mmol), iridium cyclometalated monomer shown in formula 1 of example 1 (9.6 mg, 0.01 mmol), P(o-tol)3(2.9 mg, 0.0096 mmol), dba3pd2(2.19 mg, 0.0024 mmol) were dissolved in 5 mL degassed toluene, under nitrogen protection, 120 °C for 3 h, after the reaction was completed, the reaction was dropped into 100 mL anhydrous methanol while hot, and stood for 30 min, filtered to obtain a dark green precipitate, which was dried to obtain the product, i.e. the copolymer shown in formula I.

[0064] Example 7 Formula II copolymer

[0065]

[0066] The bis-tin monomer shown in formula 24 (106.1 mg, 0.12 mmol), the bis-bromine monomer shown in formula 9 (56.8 mg, 0.11 mmol), the cyclometalated iridium monomer shown in formula 4 (9.8 mg, 0.01 mmol), P(o-tol)3 (3.0 mg, 0.010 mmol), dba3pd2 (2.4 mg, 0.0026 mmol) were dissolved in 5 mL of degassed toluene, protected by nitrogen, reacted at 120°C for 3 h, after the reaction was completed, the reaction was dropped into 100 mL of anhydrous methanol while hot, and was left for 30 min, and a dark green precipitate was obtained by filtration, which was dried to obtain the product, i.e. the copolymer shown in formula II.

[0067] The control cyclometalated iridium monomer was not fed in the ratio of 0 to the formula III control copolymer

[0068]

[0069] The bis-tin monomer shown in formula 23 (110.6 mg, 0.13 mmol), the bis-bromine monomer shown in formula 11 (36.4 mg, 0.065 mmol), the bis-bromine monomer shown in formula 6 (43.2 mg, 0.065 mmol), P(o-tol)3 (3.0 mg, 0.010 mmol), dba3pd2 (2.4 mg, 0.0026 mmol) were dissolved in 5 mL of degassed toluene, protected by nitrogen, reacted at 120°C for 3 h, after the reaction was completed, the reaction was dropped into 100 mL of anhydrous methanol while hot, and was left for 30 min, and a dark green precipitate was obtained by filtration, which was dried to obtain the product, i.e. the copolymer shown in formula III.

[0070] The cyclometalated iridium monomer was fed in the ratio of 0.01 to the formula III copolymer

[0071] The bis-tin monomer shown in formula 23 (110.6 mg, 0.13 mmol), the bis-bromine monomer shown in formula 11 (35.7 mg, 0.0637 mmol), the bis-bromine monomer shown in formula 6 (42.3 mg, 0.0637 mmol), the cyclometalated iridium monomer shown in formula 1 (2.5 mg, 0.0026 mmol), P(o-tol)3 (3.0 mg, 0.010 mmol), dba3pd2 (2.4 mg, 0.0026 mmol) were dissolved in 5 mL of degassed toluene, protected by nitrogen, reacted at 120°C for 3 h, after the reaction was completed, the reaction was dropped into 100 mL of anhydrous methanol while hot, and was left for 30 min, and a dark green precipitate was obtained by filtration, which was dried to obtain the product, i.e. the copolymer shown in formula III.

[0072]

[0073] The cyclometalated iridium monomer was fed in the ratio of 0.02 to the formula III copolymer

[0074] A double tin monomer shown in formula 23 (110.6 mg, 0.13 mmol), a double bromine monomer shown in formula 11 (33.6 mg, 0.06 mmol), a double bromine monomer shown in formula 6 (39.9 mg, 0.06 mmol), a cyclometalated iridium monomer shown in formula 1 (10.0 mg, 0.010 mmol), P(o-tol)3(3.0 mg, 0.010 mmol), dba3pd2(2.4 mg, 0.0026 mmol) were dissolved in 5 mL of degassed toluene, protected by nitrogen, reacted at 120 °C for 3 h, after the reaction was completed, the reaction was dropped into 100 mL of anhydrous methanol while hot, and stood for 30 min, and a dark green precipitate was obtained by filtration, which was dried to obtain the product, i.e., a copolymer shown in formula III.

[0075]

[0076] Example 10 Copolymer of formula III with a molar feeding ratio of cyclometalated iridium monomer of 0.04

[0077] A double tin monomer shown in formula 23 (110.6 mg, 0.13 mmol), a double bromine monomer shown in formula 11 (33.6 mg, 0.06 mmol), a double bromine monomer shown in formula 6 (39.9 mg, 0.06 mmol), a cyclometalated iridium monomer shown in formula 1 (10.0 mg, 0.010 mmol), P(o-tol)3(3.0 mg, 0.010 mmol), dba3pd2(2.4 mg, 0.0026 mmol) were dissolved in 5 mL of degassed toluene, protected by nitrogen, reacted at 120 °C for 3 h, after the reaction was completed, the reaction was dropped into 100 mL of anhydrous methanol while hot, and stood for 30 min, and a dark green precipitate was obtained by filtration, which was dried to obtain the product, i.e., a copolymer shown in formula III.

[0078]

[0079] Example 11 Copolymer of formula III with a molar feeding ratio of cyclometalated iridium monomer of 0.06

[0080] Weigh out the following: 110.6 mg (0.13 mmol) of the bistin monomer shown in Formula 23, 31.9 mg (0.057 mmol) of the bisbromo monomer shown in Formula 11, 37.9 mg (0.057 mmol) of the bisbromo monomer shown in Formula 6, 15.3 mg (0.016 mmol) of the cycloiridium monomer shown in Formula 1, P(o-tol)3 (3.0 mg (0.010 mmol), and dba3pd2 (2.4 mg (0.0026 mmol) and dissolve them in 5 mL of degassed toluene. Under nitrogen protection, react at 120 °C for 3 h. After the reaction is complete, add the hot reaction mixture dropwise into 100 mL of anhydrous methanol. Let stand for 30 min, filter to obtain a dark green precipitate, and dry to obtain the product, which is the copolymer shown in Formula III.

[0081]

[0082] Example 12 Preparation of Nanoparticles

[0083] Weigh 1 mg of the copolymer prepared in the control example and Examples 8-11, and 10 mg of the amphiphilic polymer DSPE-PEG, respectively, and place them in a small EP tube containing 1 mL of THF. Heat until both components are completely dissolved, and add them dropwise under sonication to a 25 mL vial containing 10 mL of water. Dialyze the vial for 12 h using a dialysis bag with a molecular weight cutoff of 3500. Centrifuge the dialysate at 3000 rpm for 3 min, discard the precipitate, and prepare nanomicelle systems N1-N5 with different iridium contents (representing iridium doping molar ratios of 0, 0.01, 0.02, 0.04, and 0.06, respectively).

[0084] The particle size was determined using dynamic light scattering (DLS), and the results are as follows: Figure 1 As shown, its average particle size (z-average) is about 100 nm, and its polymer dispersity index (PDI) is less than 0.3.

[0085] The ultraviolet absorption was measured using a UV-2450PC spectrophotometer (Shimazu), and the results are as follows: Figure 2 As shown, by Figure 2 It can be seen that the dye-encapsulated nanomicelles have strong absorption in the range of 600-1300.

[0086] The dye-encapsulated nanomicelle system was illuminated with a 1.0W infrared LED lamp, and the temperature change curve of the dye-encapsulated nanomicelle system over time was measured, as shown in the figure. Figure 3 As shown, the system temperature increases with time, and the temperature increase ΔT can reach 30℃ after 10 minutes.

[0087] The co-localization of N1-N5 cells with different organelles was observed using confocal microscopy. For example...Figures 4-1 to 4-4 As shown (representing the Pearson's colocalization coefficient (PCC) of nanoparticles with mitochondria, lysosome, endoplasmic reticulum and the relative content of nanoparticles in the above three organelles with different iridium contents, respectively), the PCC of N1 with endoplasmic reticulum, mitochondria and lysosome was less than 0.5, indicating non-specific organelle targeting. With the increase of iridium doping amount, the mitochondrial targeting of nanoparticles was enhanced, and the mitochondrial targeting of N3 was the strongest, with the PCC value of 0.76. In addition, with the further increase of Ir content, the colocalization of nanoparticles with mitochondria decreased, while the colocalization with endoplasmic reticulum increased. From N2 to N5, the PCC of nanoparticles with endoplasmic reticulum increased from 0.35 to 0.67, indicating that with the increase of iridium doping amount within a certain range, the organelle targeting of nanoparticles changed from non-targeting to mitochondria, and then to endoplasmic reticulum.

[0088] The above merely describes preferred specific embodiments of the present application, but the protection scope of the present application is not limited thereto, and any person skilled in the art can easily think of changes or replacements within the technical scope disclosed by the present application, which should be covered within the protection scope of the present application. Therefore, the protection scope of the present application should be subject to the protection scope of the claims.

Claims

1. An iridium-doped copolymer, characterized by, The iridium-doped copolymer is obtained by polymerization of a cyclometalated iridium monomer, a conjugated dibromide monomer and a ditin monomer; The cyclometalated iridium monomer has a double bromine functional group that can participate in polymerization; The bismuth monomer contains two trimethylbismuth groups, the sum of the molar number of the cyclometalated iridium monomer and the conjugated dibromide monomer, and the molar number of the bismuth monomer are in a ratio of 1-1.2:1-1.2, and the structure of the cyclometalated iridium monomer can be summarized as wherein The ligand includes at least one of ​ C^N ligands include at least one of 2. The iridium-doped copolymer of claim 1, wherein The cyclometallated iridium monomer includes at least one of the following compounds:

3. The iridium-doped copolymer of claim 1, wherein The conjugated dibromide monomer is selected from one or more of the following compounds, 4. The iridium-doped copolymer of claim 1, wherein The ditin monomer includes one or more of the following compounds:

5. The iridium-doped copolymer of claim 1, wherein The iridium-doped copolymer includes at least one of the following: wherein x, y, z represent the degree of polymerization, each independently takes a value of 0-10, and is not 0; r represents random copolymerization.

6. A process for the preparation of the iridium-doped copolymer according to any one of claims 1 to 5, characterized in that, The method comprises polymerizing the cyclometalated iridium monomer, the conjugated dibromide monomer and the ditin monomer in an organic solvent.

7. The method for preparing the iridium-doped copolymer according to claim 6, characterized in that, The organic solvent includes anhydrous toluene.

8. Use of the iridium-doped copolymer of any one of claims 1-5 in the preparation of a nanodrug.

9. A nanomedicine, characterized in that, The nanodrug includes: a) an amphiphilic polymer; and b) the iridium-doped copolymer of any one of claims 1-5.

10. The nanomedicine of claim 9, wherein, The cell organelle targeting of the nanodrug can be regulated by regulating the content of the doped iridium in the iridium-doped copolymer.

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