Photoresponsive polymeric copper ionophore

Abstract

The application relates to the fields of biomedical polymer materials and tumor treatment technologies, in particular to a light-responsive high-molecular copper ion carrier. The high-molecular copper ion carrier is a nanoparticle formed by self-assembly of a porphyrin-copper coordination high molecule; the porphyrin-copper coordination high molecule comprises a high-molecular skeleton, a porphyrin functional unit covalently connected with the high-molecular skeleton and Cu 2+ ; the high-molecular skeleton comprises a polyethylene glycol segment and a functional segment with a porphyrin connecting site; the porphyrin functional unit has a porphyrin macrocycle structure, and the periphery of the porphyrin macrocycle has two carboxyl-containing side chains; and the Cu 2+ is coordinated with nitrogen atoms in the porphyrin macrocycle of the porphyrin functional unit. The application improves the delivery efficiency of copper ions into tumor cells, and combines photodynamic action and copper death effect to enhance the tumor cell killing ability.

Description

Technical Field

[0001] This invention relates to the field of biomedical polymer materials and tumor treatment technology, and in particular to a photoresponsive polymeric copper ion carrier. Background Technology

[0002] Copper is one of the essential trace elements for the human body, participating in a variety of physiological and biochemical processes. Intracellular copper homeostasis is strictly regulated, and copper ions can serve as cofactors or structural components of various proteins or enzymes, participating in physiological processes such as energy metabolism, mitochondrial respiration, and redox balance.

[0003] Recent studies have discovered that abnormal accumulation of intracellular copper ions can induce a regulated form of cell death distinct from known cell death mechanisms such as apoptosis, necrosis, and ferroptosis—namely, copper death. Copper death is closely related to mitochondrial metabolism, and excessive copper ions can act on related metabolic processes and cause cytotoxicity. Based on this mechanism, inducing tumor cell death by regulating copper homeostasis within tumor cells has gradually become one of the research directions in the field of cancer therapy.

[0004] However, complex mechanisms regulate copper homeostasis within organisms, and the distribution, transport, and metabolism of copper ions are influenced by various factors. Direct use of free copper ions not only makes effective regulation of intracellular copper levels difficult, but its bioavailability and therapeutic efficacy are also easily affected by factors such as the drug administration environment. Therefore, recent studies have attempted to use nanomaterials, polymers, or other delivery systems to load or bind copper ions to improve their delivery and utilization in biomedical applications. The experiments in the original disclosure primarily focused on validating the copper loading capacity of the carrier and its intracellular copper delivery capabilities.

[0005] On the other hand, photodynamic therapy (PDT) is a method that utilizes photosensitizers to generate reactive oxygen species (ROS) under irradiation with light of a specific wavelength, thereby exerting a therapeutic effect on diseased tissues. Because light irradiation allows for a degree of spatiotemporal control of the therapeutic effect, PDT has become an important research direction in the field of tumor treatment. Porphyrins and their derivatives possess typical photosensitizing properties and are commonly used photosensitizing materials in PDT research. The original disclosure also used the generation of ROS under light irradiation as an important aspect of evaluating carrier function.

[0006] With a deeper understanding of the mechanisms of tumor development and progression, the construction of combined therapeutic systems utilizing the complementarity of different mechanisms of action has attracted widespread attention. Combining photoresponsive therapy with metal ion-mediated cell death mechanisms provides a research direction for improving the functionality of tumor treatment systems. However, the physicochemical properties, mechanisms of action, and biological behaviors of different functional components vary, and there is still room for further research and improvement in how to construct material systems suitable for biomedical applications and achieve corresponding therapeutic functions. Therefore, it is necessary to further develop functional materials with good application potential to provide new technological options for copper ion-mediated tumor therapy and its combined application with photoresponsive therapy. Summary of the Invention

[0007] This invention covers the following technical solutions: One aspect of the present invention relates to a photoresponsive polymeric copper ion carrier, wherein the polymeric copper ion carrier is a nanoparticle formed by the self-assembly of porphyrin-copper coordination polymer; The porphyrin-copper coordination polymer comprises a polymer backbone, porphyrin functional units covalently linked to the polymer backbone, and Cu groups coordinated to the porphyrin functional units. 2+ ; The polymer backbone includes polyethylene glycol segments and functionalized segments with porphyrin linking sites; The porphyrin functional unit has a porphyrin macrocyclic structure, and the porphyrin macrocyclic ring has two carboxyl-containing side chains on its periphery; the Cu 2+ It coordinates with the nitrogen atom in the porphyrin macrocycle of the porphyrin functional unit.

[0008] This invention does not simply combine porphyrin structures with copper ions, but rather constructs a photoresponsive copper ion carrier based on the structural design of polymer materials. Porphyrin functional units are covalently introduced into a polymer backbone containing polyethylene glycol segments and functionalized segments, and further, the porphyrin macrocycle is utilized in conjunction with Cu... 2+ A coordination structure is formed, enabling the resulting porphyrin-copper coordination polymer to self-assemble into nanoparticles. Therefore, the technical feature of this invention lies not only in utilizing porphyrin to achieve Cu... 2+ The loading and photoresponse are enhanced by the design of specific polymer backbones and their functionalized structures, which integrate porphyrin photosensitivity and Cu. 2+ Coordination and delivery functions are integrated into a polymer nanosystem, thereby enabling copper ion delivery under photoresponsive conditions and inducing copper death-related antitumor effects.

[0009] In some embodiments, the polyethylene glycol segments are derived from monomethoxy polyethylene glycol. In some embodiments, the number-average molecular weight of the monomethoxy polyethylene glycol is 4000 Da to 6000 Da.

[0010] In some implementations, the functionalized chain segment is composed of ( S It is constructed from ethyl 2,6-diisocyanohexanoate, 2,2′-[propane-2,2-dimethylbis(thio)]diethanol, and 3-mercapto-1,2-propanediol. In some embodiments, the polymer backbone has a composition of... N -(2-aminoethyl)maleimide introduces porphyrin linking sites.

[0011] In some embodiments, the porphyrin functional unit is derived from 3,3′-(3,7,12,17-tetramethyl-8,13-divinyl-2,18-porphyrin)dipropionic acid.

[0012] In some embodiments, the particle size of the photoresponsive polymeric copper ion support is 120 nm to 125 nm. In some embodiments, the polydispersity index (PDI) of the photoresponsive polymeric copper ion support is ≤0.15. In some embodiments, the zeta potential of the photoresponsive polymeric copper ion support is -12 mV to -10 mV.

[0013] Another aspect of the present invention relates to a method for preparing the above-mentioned photoresponsive polymeric copper ion support, the method comprising the following steps: 1) coupling a porphyrin compound having two carboxyl-containing side chains with a polymer backbone having polyethylene glycol segments and porphyrin linkage sites, thereby covalently linking the porphyrin compound with the polymer backbone to obtain a porphyrin-modified polymer; 2) reacting the porphyrin-modified polymer with a Cu-containing... 2+ The copper salt undergoes a coordination reaction, causing Cu... 2+ The porphyrin-copper coordination polymer is obtained by coordinating with the macrocyclic porphyrin in the porphyrin-modified polymer; 3) The porphyrin-copper coordination polymer is dissolved in an organic solvent and the resulting solution is added to the aqueous phase to allow the porphyrin-copper coordination polymer to self-assemble into nanoparticles.

[0014] In some embodiments, the coupling reaction in step 1) occurs in a carbodiimide condensing agent and N The process is carried out in the presence of 1-hydroxysuccinimide. In some embodiments, the carbodiimide condensing agent is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or a salt thereof.

[0015] In some embodiments, the polymeric backbone having polyethylene glycol segments and porphyrin linking sites is prepared by the following method: (…) S Ethyl 2,6-diisocyanohexanoate, 2,2′-[propane-2,2-dimethylbis(thio)]diethanol, and 3-mercapto-1,2-propanediol were reacted, followed by the addition of monomethoxy polyethylene glycol to continue the reaction, yielding a polymer containing polyethylene glycol segments; the polymer containing polyethylene glycol segments was then reacted with... N-(2-aminoethyl)maleimide or its salt is reacted to obtain the polymer backbone having polyethylene glycol segments and porphyrin linking sites. In some embodiments, the ( S The molar ratio of ethyl 2,6-diisocyanohexanoate, 2,2′-[propane-2,2-dimethylbis(thio)]diethanol and 3-mercapto-1,2-propanediol is (9-13):(3-5):(5-7).

[0016] In some embodiments, in step 1), the mass ratio of the polymeric framework to the porphyrin compound is 1:(2.0 to 2.5).

[0017] In some embodiments, in step 2), the Cu-containing... 2+ The copper salt is copper chloride.

[0018] In some embodiments, the coordination reaction is carried out under an inert atmosphere and in the dark.

[0019] In some embodiments, in step 3), the organic solvent is dimethyl sulfoxide, the aqueous phase is water, and the volume ratio of dimethyl sulfoxide to water is 1:(5-20).

[0020] Another aspect of the present invention relates to the use of the above-mentioned photoresponsive polymeric copper ion carrier in the preparation of a medicament for treating tumors; said medicament is used in combination with light irradiation to treat tumors.

[0021] In some embodiments, the tumor is selected from at least one of breast cancer, osteosarcoma, and bladder cancer.

[0022] In some embodiments, the wavelength of the light is 600 nm to 700 nm, preferably 640 nm to 660 nm.

[0023] This invention covalently links porphyrin functional units to a functionalized polymer backbone with polyethylene glycol segments, and utilizes the nitrogen atom in the porphyrin macrocycle and Cu... 2+ The formation of a coordination structure integrates the photoresponsive properties of porphyrin, the biological effects of copper ions, and the delivery function of the polymeric carrier into a single polymeric system. Furthermore, the resulting porphyrin-copper coordination polymer can self-assemble into nanoparticles under aqueous conditions, thereby forming a polymeric nanosystem suitable for copper ion loading and delivery.

[0024] Without being limited by any specific theory, this invention proposes that porphyrin macrocycles can, on the one hand, act as Cu... 2+The coordination structure of the porphyrin allows copper ions to bind in a coordinated manner within the polymer system. Furthermore, the porphyrin conjugated structure can generate reactive oxygen species under suitable wavelengths of light, thus exerting a photodynamic effect. The polyethylene glycol segments in the polymer backbone impart suitable hydrophilic properties to the resulting material and facilitate the dispersion of the porphyrin-copper coordination polymer in the aqueous phase and the formation of nanostructures. Therefore, copper ion delivery and photoresponsiveness can be achieved within the same nanocarrier system.

[0025] The nanocarrier formed by this invention can deliver copper ions into tumor cells. After accumulation within the cells, copper ions can affect copper homeostasis and cellular metabolic processes related to copper death. Simultaneously, under light irradiation, the porphyrin functional units can generate reactive oxygen species and exert photodynamic effects. Therefore, the photoresponsive polymeric copper ion carrier of this invention combines copper ion-mediated cell death with photodynamic effects, providing a combined therapeutic system with different mechanisms of action for tumor treatment.

[0026] The present invention has at least the following beneficial effects: (1) This invention covalently links porphyrin functional units onto a functionalized polymer backbone and makes Cu 2+ By coordinating with the nitrogen atom in the porphyrin macrocycle, a porphyrin-copper coordination polymer was constructed, integrating the photosensitizing function and the copper ion loading function into the same polymer system.

[0027] (2) The porphyrin-copper coordination polymer of the present invention can be further self-assembled to form nanoparticles. The resulting nanocarrier has good dispersion and physicochemical stability, and can improve the delivery of copper ions into tumor cells.

[0028] (3) The photoresponsive polymeric copper ion carrier of the present invention can generate reactive oxygen species under light conditions, and can increase the copper content in tumor cells and induce cell changes related to copper death, thereby achieving the synergistic effect of photodynamic action and copper ion-mediated cell death.

[0029] (4) This invention utilizes the photoresponse characteristics of porphyrin and Cu 2+ The combination of coordination and delivery functions with the properties of polymer nanocarriers in the same material system provides a new material basis and technological options for copper ion-mediated tumor therapy and its combined application with photodynamic therapy. Attached Figure Description

[0030] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0031] Figure 1 X-ray photoelectron spectroscopy of porphyrin-copper coordination compounds; Figure 2 Transmission electron microscopy image of a photoresponsive polymeric copper ion support; Figure 3 This is an elemental distribution diagram of a photoresponsive polymeric copper ion carrier. Figure 4 The results show the ROS generation capacity of the photoresponsive polymeric copper ion carrier. Figure 5 The in vitro copper ion release curve of the photoresponsive polymeric copper ion carrier; Figure 6 The effects of photoresponsive polymeric copper ion carriers on the viability of various tumor cells; Figure 7 The results of detecting intracellular copper content using atomic absorption spectroscopy; Figure 8 The results of CLSM characterization of intracellular DLAT protein; Figure 9 This is a Bio-TEM image of cells treated with a photoresponsive polymeric copper ion carrier.

[0032] Figure 10 The image shows a comparison of the appearance of unloaded copper ion polymer nanoparticles (NP) and photoresponsive polymer copper ion carriers (Cu-NP), with the left image showing NP and the right image showing Cu-NP. Detailed Implementation

[0033] The embodiments of the present invention will now be described in detail. The following examples are only used to explain the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. After reading this specification, those skilled in the art can make various modifications, substitutions or variations to the technical solutions of the present invention without departing from the concept and technical principles of the present invention, and all such modifications, substitutions or variations should fall within the scope of protection of the present invention.

[0034] Unless otherwise stated, the technical and scientific terms used herein have the meanings commonly understood by one of ordinary skill in the art. Unless otherwise specified, the experimental methods described herein can be performed under standard experimental conditions, in relevant laboratory manuals, or according to the recommendations of reagent or instrument manufacturers, or using other equivalent methods known in the art.

[0035] The terms "comprising," "including," and "containing" as used herein are open-ended expressions, and unless explicitly specified, they do not exclude the presence of other components, steps, or structures not explicitly listed. The terms "preferred," "optional," and "optional" as used herein are only for illustrating some embodiments and do not constitute a limitation on the scope of protection of this invention.

[0036] Unless otherwise specified, the numerical ranges mentioned in this article include any integers, fractions, decimals, and their upper and lower limits within that range.

[0037] Unless otherwise specified, the singular expressions such as "a," "a kind," and "the" used in this article also include the plural forms; "multiple" usually refers to two or more.

[0038] As used in this document, the term "and / or" refers to any one or any combination of the relevant objects.

[0039] Where there is no contradiction, the technical features of the various embodiments and examples in this specification can be combined with each other. Any conventional adjustments, substitutions, or equivalent modifications made by those skilled in the art based on the content of this specification should be considered part of the disclosure herein.

[0040] The references cited in this invention are only used to illustrate the background technology or related technical content of this invention, and their disclosures may be used for reference only if they do not conflict with the technical solutions of this invention.

[0041] In this invention, "porphyrin-copper coordination polymer" refers to a polymer containing porphyrin functional units covalently linked to the polymer backbone, and Cu 2+ A polymer that forms a coordination structure with the porphyrin functional unit. The Cu... 2+ It coordinates with the nitrogen atom in the porphyrin macrocycle, thereby enabling Cu to... 2+ It is incorporated into the polymer system. The porphyrin-copper coordination polymer can self-assemble into nanoparticles in an aqueous phase through intermolecular and / or intramolecular interactions.

[0042] In this invention, the "polymer framework" refers to a polymer structure used to support porphyrin functional units and participate in the formation of nanoparticles. The polymer framework can be formed through covalent linkages between different chain segments and may further include Cu without affecting its porphyrin linkage. 2+ Other structural units with coordination and self-assembly functions.

[0043] In this invention, a "polyethylene glycol segment" refers to a polymeric segment containing repeating oxyethylene structural units. The polyethylene glycol segment may be derived from polyethylene glycol or its end-group modified derivatives.

[0044] In this invention, a "functionalized segment" refers to a segment in the polymer backbone that has a functional structure capable of forming a covalent bond with a porphyrin compound, either directly or indirectly. The functionalized segment provides one or more porphyrin linking sites, thereby enabling the porphyrin functional unit to be covalently linked to the polymer backbone.

[0045] In this invention, a "porphyrin linking site" refers to a reactive structure or functional group located on the polymer backbone that can directly or through a coupling reaction form a covalent bond with a porphyrin compound. The specific structure of the porphyrin linking site is not particularly limited, as long as it enables the porphyrin functional unit to be stably covalently linked to the polymer backbone.

[0046] In this invention, "porphyrin functional unit" refers to a unit that has a porphyrin macrocyclic structure and can react with Cu. 2+ The structural unit undergoes coordination and exhibits photoresponsive properties. The porphyrin functional unit is covalently linked to the polymer backbone and interacts with Cu atoms in the porphyrin macrocycle. 2+ Formation of coordination structures.

[0047] In this invention, a "porphyrin macrocycle" refers to a conjugated macrocyclic structure formed by four pyrrole subunits linked by a bridging structure, containing nitrogen atoms capable of coordinating with metal ions. The periphery of the porphyrin macrocycle may have substituents, without affecting its interaction with Cu. 2+ In the case of coordination and photoresponsive functions, the specific structure of the peripheral substituents can be selected according to the connection requirements between the porphyrin functional unit and the polymer backbone.

[0048] In this invention, a "carboxyl-containing side chain" refers to a side chain structure located on the periphery of the porphyrin macrocycle and containing at least one carboxyl group. The carboxyl group can exist directly in the side chain or, under coupling reaction conditions, in a form capable of participating in the formation of a covalent bond. The carboxyl-containing side chain provides the reaction site required for the formation of a covalent bond between the porphyrin compound and the polymer backbone. The porphyrin functional unit in this invention has two of the aforementioned carboxyl-containing side chains.

[0049] In this invention, "coordination" refers to Cu 2+ It forms coordination interactions with the coordinating atoms in the porphyrin macrocycle.

[0050] In this invention, "self-assembly" refers to the process by which porphyrin-copper coordination polymers spontaneously form aggregates with nanoscale structures under suitable medium conditions through hydrophobic interactions, π-π interactions, intermolecular forces and / or other non-covalent interactions.

[0051] In this invention, "nanoparticles" refers to nanoscale particles formed by the self-assembly of the porphyrin-copper coordination polymer.

[0052] In this invention, "copper death" refers to a form of regulated cell death associated with abnormal accumulation of copper ions in cells.

[0053] In this invention, "light irradiation" refers to irradiating the photoresponsive polymer copper ion carrier with light that can excite the porphyrin functional unit to produce a photoresponse.

[0054] Photoresponsive polymeric copper ion carrier This invention provides a photoresponsive polymeric copper ion carrier, wherein the polymeric copper ion carrier is a nanoparticle formed by the self-assembly of a porphyrin-copper coordination polymer; the porphyrin-copper coordination polymer includes a polymeric backbone, porphyrin functional units covalently linked to the polymeric backbone, and Cu atoms coordinated to the porphyrin functional units. 2+ The polymer backbone includes polyethylene glycol segments and functionalized segments with porphyrin linking sites; the porphyrin functional unit has a porphyrin macrocycle structure, and the porphyrin macrocycle has two carboxyl-containing side chains on its periphery; the Cu 2+ It coordinates with the nitrogen atom in the porphyrin macrocycle of the porphyrin functional unit.

[0055] This invention integrates a polymer framework, porphyrin functional units, and Cu through the above structure. 2+ They are integrated into the same polymer system. The polymer framework supports the porphyrin functional units and provides the structural basis for the aqueous dispersion and self-assembly of the porphyrin-copper coordination polymer. The porphyrin functional units are covalently connected to the polymer framework, and the nitrogen atoms in the porphyrin macrocycle interact with Cu... 2+ It forms a coordination structure while retaining the photoresponse properties of the porphyrin structure.

[0056] The polymer backbone of the present invention includes polyethylene glycol segments and functionalized segments with porphyrin linking sites.

[0057] The polyethylene glycol segments are hydrophilic, which can improve the dispersion ability of the obtained polymer in an aqueous environment and provide a hydrophilic structural basis for the subsequent self-assembly of porphyrin-copper coordination polymers.

[0058] In some embodiments, the polyethylene glycol segments are derived from polyethylene glycol or its end-group modified derivatives. In some embodiments, the polyethylene glycol segments are derived from monomethoxy polyethylene glycol.

[0059] In some embodiments, the number-average molecular weight of the monomethoxy polyethylene glycol is 4000 Da to 6000 Da, for example, it can be 4000 Da, 4200 Da, 4500 Da, 4800 Da, 5000 Da, 5200 Da, 5500 Da, 5800 Da, or 6000 Da, as well as a range formed by any of the above values ​​as endpoints. In one specific embodiment, the monomethoxy polyethylene glycol is mPEG5000.

[0060] The functionalized segments are used to form the main structure of the polymer backbone and provide reaction sites for connecting porphyrin functional units.

[0061] In some implementations, the functionalized chain segment is composed of ( S It is constructed from ethyl 2,6-diisocyanohexanoate, 2,2′-[propane-2,2-dimethylbis(thio)]diethanol and 3-mercapto-1,2-propanediol.

[0062] In some implementations, the ( S The molar ratio of ethyl 2,6-diisocyanohexanoate, 2,2′-[propane-2,2-dimethylbis(thio)]diethanol, and 3-mercapto-1,2-propanediol is (9–13):(3–5):(5–7). For example, the molar ratio of the three can be 9:3:5, 10:4:5, 10:4:6, 11:4:6, 12:4:6, 12:5:7, or 13:5:7. In one specific embodiment, the molar ratio of the three is 11:4:6.

[0063] The polyethylene glycol segments can be introduced during the formation of the functionalized segments, or they can be introduced after the formation of the functionalized segments via a covalent reaction. In some embodiments, firstly ( S Ethyl 2,6-diisocyanohexanoate, 2,2′-[propane-2,2-dimethylbis(thio)]diethanol and 3-mercapto-1,2-propanediol were reacted, and then monomethoxy polyethylene glycol was added to continue the reaction, thereby obtaining a polymer containing polyethylene glycol segments.

[0064] The polymer containing polyethylene glycol segments can be further functionalized to introduce porphyrin linkage sites that can form covalent bonds with porphyrin compounds.

[0065] In some embodiments, the porphyrin linkage site is via N-(2-aminoethyl)maleimide or a salt thereof is introduced. In one specific embodiment, a polymer containing polyethylene glycol segments is combined with... N The reaction proceeds with (2-aminoethyl)maleimide hydrochloride to obtain a polymeric backbone with polyethylene glycol segments and porphyrin linkage sites.

[0066] The porphyrin functional unit in this invention has a porphyrin macrocyclic structure and two carboxyl-containing side chains on the periphery of the porphyrin macrocyclic structure.

[0067] The porphyrin macrocycle has a conjugated structure, enabling it to produce a photoresponse under illumination of suitable wavelengths of light, and it can react with Cu atoms in the macrocycle. 2+ A coordination structure is formed. The carboxyl-containing side chains located on the periphery of the porphyrin macrocycle can provide reactive groups for covalent bonding with the polymer backbone, thereby stably linking the porphyrin functional units to the polymer backbone.

[0068] In some embodiments, the carboxyl-containing side chain comprises a hydrocarbon group extending outward from the porphyrin macrocycle and a carboxyl group located on the hydrocarbon group. The structure and length of the carboxyl-containing side chain can be selected based on the coupling reaction between the porphyrin compound and the polymer backbone, as long as it enables the porphyrin compound to form a stable covalent bond with the polymer backbone and does not substantially affect the Cu of the porphyrin macrocycle. 2+ Coordination ability and photoresponse characteristics are sufficient.

[0069] In some embodiments, the porphyrin functional unit is derived from 3,3′-(3,7,12,17-tetramethyl-8,13-divinyl-2,18-porphyrin)dipropionic acid. The porphyrin compound has a porphyrin macrocycle and two carboxyl-containing side chains, which can participate in coupling reactions via the carboxyl-containing side chains to connect to the polymer backbone.

[0070] By covalently linking porphyrin functional units to the polymer backbone, Cu can be further... 2+ By coordinating with porphyrin functional units, porphyrin-copper coordinated polymers are obtained.

[0071] In this invention, Cu 2+ It forms a coordination structure with the nitrogen atom in the porphyrin macrocycle, allowing Cu to... 2+ This can be incorporated into porphyrin-modified polymers. In this way, the copper ion loading function and the photoresponsive function of porphyrin can be integrated into the same polymer structure.

[0072] Used to provide Cu 2+ The copper source can provide Cu in the reaction medium 2+ It forms a copper salt that coordinates with the porphyrin macrocycle. In some embodiments, the copper salt is copper chloride.

[0073] In some embodiments, porphyrin-modified polymers and Cu-containing polymers 2+ The copper salt undergoes a coordination reaction in an organic solvent. The coordination reaction can be carried out under light-protected conditions. In some embodiments, the coordination reaction can also be carried out under a nitrogen, argon, or other inert atmosphere.

[0074] Cu in the obtained porphyrin-copper coordination polymer 2+ Coordination with porphyrin macrocycles can be verified by X-ray photoelectron spectroscopy or other suitable structural characterization methods.

[0075] The porphyrin-copper coordination polymer of the present invention can self-assemble into nanoparticles in a suitable solvent environment.

[0076] In some embodiments, the porphyrin-copper coordination polymer is first dissolved in an organic solvent that allows it to dissolve or disperse sufficiently to form an organic phase, and then the organic phase is added to an aqueous phase. As the solvent environment changes, the porphyrin-copper coordination polymer undergoes self-assembly and forms nanoparticles.

[0077] The organic solvent can be an organic solvent capable of dissolving or dispersing porphyrin-copper coordination polymers and miscible with water. In some embodiments, the organic solvent is dimethyl sulfoxide. The aqueous phase can be water, such as deionized water or ultrapure water.

[0078] In some embodiments, the volume ratio of dimethyl sulfoxide to water is 1:(5-20), for example, 1:5, 1:6, 1:8, 1:10, 1:12, 1:15, 1:18, or 1:20, and a range formed by any of the above values ​​as endpoints. In one specific embodiment, the volume ratio of dimethyl sulfoxide to water is 1:10.

[0079] In some embodiments, the organic phase containing the porphyrin-copper coordination polymer is added to the aqueous phase under stirring conditions, and stirring is continued after the addition is completed to promote the formation of nanoparticles.

[0080] After self-assembly, the resulting nanoparticles can be purified by dialysis, centrifugation, filtration, or a combination thereof. The purification primarily removes organic solvents, components that did not form nanoparticles, and other small molecule impurities. The molecular weight cutoff of the dialysis membrane, dialysis time, water exchange frequency, centrifugation speed, and filter pore size can be selected based on the particle size of the obtained nanoparticles and the specific preparation scale.

[0081] In some embodiments, the particle size of the photoresponsive polymeric copper ion carrier is 120 nm to 125 nm, for example, it can be 120 nm, 121 nm, 122 nm, 123 nm, 124 nm or 125 nm, and a range formed by any of the above values ​​as endpoints.

[0082] In some embodiments, the polydispersity index (PDI) of the photoresponsive polymeric copper ion carrier is ≤0.15.

[0083] In some embodiments, the zeta potential of the photoresponsive polymeric copper ion carrier is -12 mV to -10 mV.

[0084] The particle size and polydispersity index of the nanoparticles can be determined by dynamic light scattering, and their morphology can be observed by transmission electron microscopy. In one specific embodiment, the obtained nanoparticles have a particle size of approximately 123 nm, a PDI of 0.14, a Zeta potential of -11.0 mV, and exhibit a relatively uniform spherical nanostructure.

[0085] Preparation method of photoresponsive polymeric copper ion carrier The present invention also provides a method for preparing the above-mentioned photoresponsive polymeric copper ion carrier.

[0086] The preparation method includes: firstly, a porphyrin compound having two carboxyl-containing side chains undergoes a coupling reaction with a polymer backbone having polyethylene glycol segments and porphyrin linkage sites, thereby covalently linking the porphyrin compound to the polymer backbone; subsequently, Cu... 2+ The porphyrin macrocycle in the obtained porphyrin-modified polymer is coordinated; finally, by changing the solvent environment of the obtained porphyrin-copper coordinated polymer, it is made to self-assemble into nanoparticles in the aqueous phase.

[0087] In some embodiments, a porphyrin compound having two carboxyl-containing side chains is covalently linked to the polymer backbone via a coupling reaction.

[0088] In some embodiments, the coupling reaction occurs in a carbodiimide condensing agent and N The reaction proceeds in the presence of hydroxysuccinimide. Carbodiimide condensing agents and... N -Hydroxysuccinimide can be used to activate the carboxyl groups in the carboxyl-containing side chains of porphyrin compounds to promote the formation of covalent bonds between porphyrin compounds and the polymer backbone.

[0089] In some embodiments, the carbodiimide condensing agent is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide or a salt thereof. In one specific embodiment, the carbodiimide condensing agent is 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride.

[0090] In some embodiments, the mass ratio of the polymeric backbone to the porphyrin compound is 1:(2.0 to 2.5), for example, it can be 1:2.0, 1:2.1, 1:2.2, 1:2.26, 1:2.3, 1:2.4 or 1:2.5, and a range formed by any of the above values ​​as endpoints.

[0091] The coupling reaction can be carried out in an organic solvent that can dissolve or disperse the reactants without significantly interfering with the coupling reaction. In some embodiments, the organic solvent is... N , N -Dimethylformamide.

[0092] After the coupling reaction is complete, unreacted small molecules can be removed by dialysis or other means, and porphyrin-modified polymers can be obtained by freeze drying or other suitable methods.

[0093] The obtained porphyrin-modified polymer was combined with Cu-containing... 2+ The copper salt undergoes a coordination reaction, causing Cu... 2+ Coordinated with the nitrogen atom in the porphyrin macrocycle, a porphyrin-copper coordinated polymer is obtained.

[0094] In some embodiments, the Cu-containing 2+ The copper salt is copper chloride.

[0095] The coordination reaction can be carried out in a solvent capable of dissolving or dispersing the porphyrin-modified polymer and the copper salt. In some embodiments, the solvent is... N , N -Dimethylformamide.

[0096] In some embodiments, the coordination reaction is carried out under light-protected conditions. In some embodiments, the coordination reaction is carried out under an inert atmosphere. The inert atmosphere may be nitrogen or argon.

[0097] After the coordination reaction is complete, free copper ions and other small molecules can be removed by dialysis or other methods to obtain porphyrin-copper coordinated polymers.

[0098] In some embodiments, the obtained porphyrin-copper coordination polymer is dissolved in an organic solvent, and the resulting solution is added to an aqueous phase to allow the porphyrin-copper coordination polymer to self-assemble and form nanoparticles.

[0099] In some embodiments, the organic solvent is dimethyl sulfoxide, and the aqueous phase is water.

[0100] In some embodiments, the volume ratio of the dimethyl sulfoxide to water is 1:(5-20).

[0101] In some embodiments, an organic phase containing a porphyrin-copper coordination polymer is added to an aqueous phase under stirring conditions. The addition method can be dropwise, injection, or other methods that enable rapid mixing of the organic phase and the aqueous phase.

[0102] After self-assembly to form nanoparticles, the organic solvent in the system can be removed by dialysis, and larger aggregates or other impurities can be removed by centrifugation and / or filtration, thereby obtaining a photoresponsive polymeric copper ion carrier.

[0103] Anti-tumor uses The present invention also provides the use of the photoresponsive polymeric copper ion carrier in the preparation of a medicament for treating tumors, the medicament being used in combination with light irradiation to treat tumors.

[0104] During use, the photoresponsive polymeric copper ion carrier can be taken up by tumor cells, thereby releasing Cu 2+ It is delivered into tumor cells. Intracellular copper can increase intracellular copper levels and further influence cellular processes associated with copper death.

[0105] On the other hand, the porphyrin functional units in the support exhibit photoresponsive properties and can generate reactive oxygen species under light irradiation of a suitable wavelength. Therefore, by combining the use of a photoresponsive polymeric copper ion support with light irradiation, the effects of Cu can be simultaneously utilized. 2+ Biological effects resulting from delivery and photodynamic effects generated by porphyrin functional units.

[0106] In some implementations, the tumor is a solid tumor.

[0107] In some embodiments, the tumor is selected from at least one of breast cancer, osteosarcoma, and bladder cancer.

[0108] In some embodiments, the wavelength of the light is 600 nm to 700 nm, for example, 600 nm, 620 nm, 630 nm, 640 nm, 650 nm, 660 nm, 680 nm, or 700 nm, and a range formed by any of the above values ​​as endpoints. In some preferred embodiments, the wavelength of the light is 640 nm to 660 nm. In one specific embodiment, a 650 nm laser is used for irradiation.

[0109] The concentration, administration method, light power, light exposure time, and time interval between administration and light exposure of the photoresponsive polymeric copper ion carrier can be adjusted according to the tumor type, treatment site, carrier dosage, and specific treatment needs.

[0110] In some embodiments, the photoresponsive polymeric copper ion carrier generates reactive oxygen species under light irradiation, thereby exerting a photodynamic effect on tumor cells; simultaneously, the carrier can increase the intracellular copper content of tumor cells and induce cellular changes associated with copper death. Through the combination of these different mechanisms of action, the killing effect on tumor cells can be enhanced.

[0111] The embodiments of the present invention will be described in detail below with reference to the examples. It should be understood that these embodiments are only used to illustrate the technical content of the present invention and are not intended to limit the scope of protection of the present invention. Unless otherwise specified, the specific experimental conditions in the following embodiments are given priority reference to the guidelines provided in this specification, or may be carried out according to generally accepted experimental manuals or conventional experimental conditions, or other experimental methods known in the art, or according to the conditions recommended by the relevant reagent or instrument manufacturers. In specific embodiments, unless otherwise specified, minor deviations within the weighing accuracy range are allowed for the measurement parameters involving raw material components; reasonable deviations due to instrument detection accuracy or operational accuracy are also allowed for parameters such as temperature and time.

[0112] Example 1: Synthesis and characterization of functionalized polymers and porphyrin-copper coordination compounds The preparation method of the functionalized polymer and porphyrin-copper coordination compound (Por-Cu complex, abbreviated as Por-Cu) in this embodiment is as follows: 1) Weigh out (at room temperature) S 100 mg (0.44 mmol) of ethyl 2,6-diisocyanohexanoate, 33.43 mg (0.16 mmol) of 2,2′-[propane-2,2-dimethylbis(thio)]diethanol, and 26.08 mg (0.24 mmol) of 3-mercapto-1,2-propanediol were placed in a 100 mL double-necked flask. After evacuating the flask to remove air, nitrogen gas was introduced. Then, 10 mL of anhydrous DMF was added, and the mixture was magnetically stirred at 50 °C in the dark for 24 h. After the reaction was complete, 0.92 mg (0.040 mmol) of polyethylene glycol mPEG5000 was added to the mixture, and the reaction was continued at 50 °C in the dark for another 24 h. After the reaction was complete, the solution was placed in a dialysis bag with a molecular weight cutoff of 8000 Da and dialyzed in deionized water for 48 h to remove small molecule impurities. The solution was then freeze-dried to obtain polymer P1. 1 The structure of P1 was characterized by H NMR, and the results showed that the target product was successfully synthesized.

[0113] 2) Weigh out 100 mg of the polymer P1 prepared above and N42.58 mg (0.24 mmol) of 2-(2-aminoethyl)maleimide hydrochloride was added to a 100 mL two-necked flask. After removing air from the flask, nitrogen gas was bubbled through it for protection. Then, 10 mL of anhydrous DMF was added to dissolve the solution, and the reaction was carried out at 50 °C in the dark for 24 h. After the reaction was complete, the solution was dialyzed in a dialysis bag with a molecular weight cutoff of 8000 Da for 48 h, and then freeze-dried to obtain polymer P2. 1 The structure of P2 was characterized by H NMR, and the results confirmed that the product structure was correct.

[0114] 3) Weigh out 100 mg of polymer P2, 226.10 mg (0.40 mmol) of 3,3′-(3,7,12,17-tetramethyl-8,13-divinyl-2,18-porphyrin)dipropionic acid, 61.63 mg (0.32 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and... N 7.40 mg (0.064 mmol) of hydroxysuccinimide was added to a 100 mL two-necked flask. Then, 10 mL of DMF was added, and the reaction was carried out at 50 °C in the dark for 24 h. After the reaction was complete, the solution was dialyzed for 48 h in a dialysis bag with a molecular weight cutoff of 8000 Da, and then freeze-dried to obtain the functionalized polymer P3. 1 The structure of P3 was characterized by 1H NMR, and the results showed that the porphyrin was successfully grafted onto the polymer, and the target product was successfully synthesized.

[0115] 4) Dissolve 100 mg of the prepared P3 in 10 mL of DMF, add copper chloride (CuCl2, 0.40 mmol, approximately 53.8 mg), and stir the mixture at 55 °C for 24 h under nitrogen protection and in the dark. The copper chloride is added in excess relative to the porphyrin functional unit contained in P3 to promote the reaction of the porphyrin macrocycle with Cu. 2+ Complete coordination was achieved. After the reaction was complete, the reaction solution was transferred to a dialysis bag with a molecular weight cutoff of 8000 Da and dialyzed with deionized water for 48 h, changing the water three times during this period to remove unreacted copper salts and small molecule impurities. After dialysis, the solution in the bag was freeze-dried to obtain a solid copper-containing polymer, namely the Por-Cu complex powder.

[0116] The copper content in the Por-Cu complex powder was determined using XPS (PerkinElmer, USA). The experimental results are as follows: Figure 1 As shown. By Figure 1 As can be seen, a clear Cu 2p characteristic peak appears at 936.1 eV; at the same time, the N 1s characteristic peak also supports the coordination of porphyrin with copper, indicating that Cu can coordinate with the nitrogen atom in the porphyrin macrocycle to form a Por-Cu complex.

[0117] Example 2: Preparation and characterization of photoresponsive polymeric copper ion carriers The preparation method of the photoresponsive polymeric copper ion carrier (Cu-NP) in this embodiment is as follows: 1) Dissolve 100 mg of the Por-Cu complex powder prepared in Example 1 in 1 mL of DMSO to obtain an organic phase solution.

[0118] 2) At room temperature, the above organic phase solution was injected into 10 mL of deionized water under stirring conditions, and the injection time was controlled at about 1 min; after the injection was completed, stirring was continued for 0.5 h to obtain a mixture.

[0119] 3) Transfer the above mixture to a dialysis bag with a molecular weight cutoff of 3500 Da, dialyze in deionized water for 24 h, and change the water every 6 h; then centrifuge the mixture at 3000 r / min for 5 min, filter through a 0.45 μm filter membrane and make up to 10 mL to obtain Cu-NP.

[0120] The particle size of Cu-NP was determined by dynamic light scattering (DLS). The results showed that the particle size of Cu-NP was 123 nm, the polydispersity index (PDI) was 0.14, and the zeta potential was -11.0 mV.

[0121] The morphology of Cu-NP was characterized using transmission electron microscopy (TEM), and the results are as follows: Figure 2 As shown. Figure 2 The results show that the prepared Cu-NPs exhibit a spherical nanostructure with uniform size. The elemental distribution of the Cu-NPs was characterized using scanning transmission electron microscopy (STEM) combined with energy-dispersive X-ray spectroscopy (EDX), and the results are as follows: Figure 3 As shown. Figure 3 This indicates that Cu is uniformly distributed in Cu-NP. These results demonstrate that the prepared Cu-NP has a relatively uniform particle size and morphology, and that copper is distributed within it.

[0122] The ROS generation capacity of Cu-NP was further detected using the DPBF probe method, and the results are as follows: Figure 4 As shown in the figure. The results indicate that under 650 nm laser irradiation, Cu-NP can reduce the characteristic absorption peak of the DPBF probe by more than 60% within 120 s, indicating that Cu-NP has the ability to induce reactive oxygen species generation.

[0123] The illumination parameters were: 650 nm excitation light, 2 min illumination time, and 1 W illumination power. The initial absorbance of DPBF was 0.2, and the initial absorbance of the nanoparticles was 0.8. The experiment was repeated three times.

[0124] The release of Cu NP was tested using dialysis in simulated normal (pH=7.4) and simulated tumor microenvironment (pH=6.5) environments. The dialysis bag had a molecular weight of 10 kDa, the liquid-to-internal volume ratio was 1:100, the temperature was set at 37℃, and 2% Tween 80 was added to the external liquid to achieve the leakage conditions. Samples were taken at specific time points to calculate the release ratio. The illumination parameters were: 650 nm excitation light, 2 min illumination time, and 1 W / cm² illumination power. 2 .like Figure 5 As shown.

[0125] Example 3: Effects of Cu-NP on the viability of various tumor cells The effect of Cu-NP prepared in Example 2 on the viability of various tumor cell types (4T1, MCF-7, CAL-51, K7M2, and T24) was detected using the MTT assay. Cells were cultured at 5 × 10⁶ cells per well. 3 Cells were seeded at a density of 100 μL in 96-well plates and cultured for 12 h. Cells were then incubated for 24 h with CuCl2, NP, Cu-NP, NP+L, and Cu-NP+L at final concentrations of 0.1 μM, 0.5 μM, 1 μM, 5 μM, 10 μM, and 20 μM, respectively. Subsequently, 10% MTT working solution prepared with 100 μL RPMI 1640 medium was added to each well. After culturing at 37°C for 4 h, 100 μL of 10% SDS was added to each well, and the cells were cultured at 37°C for another 12 h. Absorbance was measured at 570 nm (detection absorbance) and 650 nm (background absorbance) using a microplate reader. Cell viability was expressed as the ratio of absorbance in test wells to absorbance in control wells. The light power for the NP+L and Cu-NP+ groups was as described in Example 2.

[0126] MTT test results are as follows Figure 6 As shown. The results indicated that Cu-NP+L was significantly more toxic to the aforementioned tumor cell lines than other control groups, and this toxicity was concentration-dependent; in 4T1 cells, its IC50 value was significantly higher. 50 At concentrations as low as 1.25 μM, it exhibited strong in vitro cytotoxicity against a variety of tested tumor cells.

[0127] Example 4: Cu-NP delivers copper ions into tumor cells Intracellular copper content was detected using atomic absorption spectrometry (AAS). Cells containing 4 × 10⁻⁶ copper were analyzed. 6Two mL of culture medium was seeded into each 4T1 cell in a six-well plate and cultured for 12 h in an incubator. After complete cell adhesion, CuCl2 and Cu-NP solutions were added to bring the final Cu concentration to 2 μM. Three replicates were set up for each group, with the PBS group serving as a control. After 4 h of drug treatment, the culture medium was aspirated, and the cells were gently washed three times with cold PBS to remove any Cu that had not yet entered the cells. The six-well plate was placed in a fume hood, and 100 μL of concentrated HNO3 and 100 μL of 30% H2O2 solution were added to each well. After 4 h of digestion, the digest was collected and brought to a final volume of 2 mL. The copper content was determined using an anabolic osmotic pressure (AAS) assay.

[0128] The results are as follows Figure 7 As shown. Figure 7 The results indicate that the intracellular copper content in Cu-NP-treated cells was 3.2 times that in the CuCl2-treated group. These results demonstrate that Cu-NP can deliver copper ions into 4T1 cells more efficiently than CuCl2.

[0129] Example 5: Cu-NP-induced copper death The morphology of intracellular DLAT protein was characterized using confocal laser scanning microscopy (CLSM). A coverslip was placed at the bottom of each well in a 24-well plate, and 1 mL of a solution containing 6 × 10⁶ ppm of DLAT protein was added to each well. 4 Four T1 cells were cultured in the same medium as Cu-NP prepared in Example 2 for 12 h. A laser irradiation group was also included, and 650 nm laser irradiation was performed 6 h after drug administration. After treatment, the medium was removed, and the cells were washed three times with PBS. DLAT rabbit polyclonal antibody was added, and the cells were incubated at 37°C for 1 h. After washing three times with PBS, goat anti-rabbit IgG H+L (Alexa Fluor 488) was added, and the cells were incubated at 37°C for 1 h. The cells were washed three times again with PBS, and coverslips were placed on a microscope slide. Cell nuclei were stained with DAPI, and the morphology of intracellular DLAT protein was observed using CLSM. The light power for the Cu-NP+L group was the same as in Example 2.

[0130] CLSM results as follows Figure 8 As shown. Figure 8 The results showed that DLAT protein was distributed in punctate clusters in Cu-NP+L treated 4T1 cells, indicating that DLAT protein aggregation occurred, which is a typical feature of copper death.

[0131] 4T1 cells were seeded at a density of 800,000 cells per dish in 10 cm culture dishes and incubated at 37°C for 12 h. Cells were then treated with Cu-NP prepared in Example 2 at a final concentration of 2 μM for 12 h, while a laser irradiation group was also included. Cells were collected, fixed with electron microscopy fixative, and electron microscopy samples were prepared for observation using a biological transmission electron microscope (Bio-TEM).

[0132] Bio-TEM results are as follows Figure 9 As shown. Figure 9 This indicates that Cu-NP+L treatment of 4T1 cells resulted in severe mitochondrial damage, mainly manifested as mitochondrial atrophy, increased mitochondrial membrane density, and a reduction or even disappearance of mitochondrial cristae, which is consistent with the mitochondrial morphological characteristics associated with copper death.

[0133] The above results indicate that the photoresponsive polymeric copper ion carrier of the present invention can increase the copper content in tumor cells, enhance reactive oxygen species generation and tumor cell killing under laser irradiation, and induce cellular changes related to copper death, such as DLAT protein aggregation and mitochondrial damage.

[0134] The embodiments described above are merely illustrative of several implementations of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of protection of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these all fall within the scope of protection of the present invention. The scope of protection of the present invention should be determined by the appended claims, and the specification and drawings can be used to interpret the content of the claims.

Claims

1. A photoresponsive polymeric copper ion carrier, characterized in that, The polymeric copper ion carrier is a nanoparticle formed by the self-assembly of porphyrin-copper coordination polymer; The porphyrin-copper coordination polymer comprises a polymer backbone, porphyrin functional units covalently linked to the polymer backbone, and Cu. 2+ ; The polymer backbone includes polyethylene glycol segments and functionalized segments with porphyrin linking sites; The porphyrin functional unit has a porphyrin macrocyclic structure, and the porphyrin macrocyclic ring has two carboxyl-containing side chains on its periphery; the Cu 2+ It coordinates with the nitrogen atom in the porphyrin macrocycle of the porphyrin functional unit.

2. The photoresponsive polymeric copper ion carrier according to claim 1, characterized in that, The polyethylene glycol segments are derived from monomethoxy polyethylene glycol; Optionally, the number-average molecular weight of the monomethoxy polyethylene glycol is 4000 Da to 6000 Da.

3. The photoresponsive polymeric copper ion carrier according to claim 2, characterized in that, The functionalized chain segment consists of ( S Constructed from ethyl 2,6-diisocyanohexanoate, 2,2′-[propane-2,2-diylbis(thio)]diethanol and 3-mercapto-1,2-propanediol; Optionally, the polymeric framework has a structure composed of... N -(2-aminoethyl)maleimide introduces porphyrin linking sites.

4. The photoresponsive polymeric copper ion carrier according to claim 1, characterized in that, The porphyrin functional unit is derived from 3,3′-(3,7,12,17-tetramethyl-8,13-divinyl-2,18-porphyrin)dipropionic acid.

5. The photoresponsive polymeric copper ion carrier according to any one of claims 1 to 4, characterized in that, The particle size of the photoresponsive polymeric copper ion carrier is 120 nm to 125 nm. Optionally, its polydispersity index (PDI) ≤ 0.15; Optionally, its Zeta potential is -12 mV to -10 mV.

6. A method for preparing a photoresponsive polymeric copper ion carrier according to any one of claims 1 to 5, characterized in that, Includes the following steps: 1) A porphyrin compound having two carboxyl-containing side chains is coupled to a polymer backbone having polyethylene glycol segments and porphyrin linkage sites, thereby covalently linking the porphyrin compound to the polymer backbone to obtain a porphyrin-modified polymer. 2) The porphyrin-modified polymer is combined with Cu-containing... 2+ The copper salt undergoes a coordination reaction, causing Cu... 2+ By coordinating with the porphyrin macrocycle in the porphyrin-modified polymer, a porphyrin-copper coordinated polymer is obtained; 3) Dissolve the porphyrin-copper coordination polymer in an organic solvent and add the resulting solution to the aqueous phase to allow the porphyrin-copper coordination polymer to self-assemble into nanoparticles.

7. The preparation method according to claim 6, characterized in that, The coupling reaction in step 1) occurs in a carbodiimide condensing agent and N The procedure was carried out in the presence of 1-hydroxysuccinimide; Optionally, the carbodiimide condensing agent is 1-ethyl-(3-dimethylaminopropyl)carbodiimide or a salt thereof.

8. The preparation method according to claim 6, characterized in that, The polymeric framework having polyethylene glycol segments and porphyrin linking sites is prepared by the following method: Will( S Ethyl 2,6-diisocyanohexanoate, 2,2′-[propane-2,2-dimethylbis(thio)]diethanol and 3-mercapto-1,2-propanediol were reacted, and then monomethoxy polyethylene glycol was added to continue the reaction to obtain a polymer containing polyethylene glycol segments. The polymer containing polyethylene glycol segments and N -(2-aminoethyl)maleimide or its salt is reacted to obtain the polymer backbone having polyethylene glycol segments and porphyrin linkage sites; Optionally, the ( S The molar ratio of ethyl 2,6-diisocyanohexanoate, 2,2′-[propane-2,2-dimethylbis(thio)]diethanol and 3-mercapto-1,2-propanediol is (9-13):(3-5):(5-7).

9. The preparation method according to any one of claims 6 to 8, characterized in that, In step 1), the mass ratio of the polymeric framework to the porphyrin compound is 1:(2.0-2.5); Optionally, in step 2), the Cu-containing 2+ The copper salt is copper chloride; Optionally, the coordination reaction is carried out under an inert atmosphere and in the dark. Optionally, in step 3), the organic solvent is dimethyl sulfoxide, the aqueous phase is water, and the volume ratio of dimethyl sulfoxide to water is 1:(5-20).

10. Use of the photoresponsive polymeric copper ion carrier according to any one of claims 1 to 5 in the preparation of a medicament for treating tumors; said medicament is used in combination with light irradiation for the treatment of tumors; Optionally, the tumor is selected from at least one of breast cancer, osteosarcoma, and bladder cancer; Optionally, the wavelength of the light is 600 nm to 700 nm; preferably 640 nm to 660 nm.

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