Acidic tumor microenvironment activated nanoprobe as well as synthesis method and application thereof

Abstract

The invention discloses an acidic tumor microenvironment activated nano probe as well as a synthesis method and application thereof, and belongs to the technical field of nano material preparation. In order to solve the problems of low treatment efficiency, lack of tumor targeting and the like caused by limitation of hypoxia of a tumor microenvironment when the existing photosensitizer is applied to a photodynamic therapy (PDT) process, a metal Fe < 2 + >, an anti-angiogenic drug thalidomide and a photosensitizer hematoporphyrin monomethyl ether approved by FDA are self-assembled, so that the anti-angiogenic drug thalidomide is prepared. The low pH response type intelligent nano diagnosis and treatment probe is prepared. Before the probe is degraded at a tumor part, the photodynamic therapy performance is opened, and a magnetic resonance imaging (MRI) signal is closed. Along with continuous enrichment of the material in tumor tissues, under low-pH stimulation of a tumor microenvironment, an MRI signal is gradually opened and thalidomide is released, oxidative stress is amplified by increasing ROS / consuming GSH, tumor cell ferroptosis is induced, and finally an excellent anti-tumor effect is achieved in cooperation with chemical kinetics / chemotherapy / photodynamic force.

Description

Technical Field

[0001] The present invention belongs to the technical field of nano material preparation, and in particular relates to an acidic tumor microenvironment activated nano probe and a synthesis method and application thereof. Background Art

[0002] Malignant tumors have always been one of the diseases that seriously threaten human health. Currently, clinical treatments for cancer mainly include surgical resection, chemotherapy, and radiotherapy. However, these strategies have certain limitations in terms of significant damage to normal tissues and hypoxic tumor microenvironment (TME) and high systemic toxicity.

[0003] In recent years, photodynamic therapy (PDT) has emerged as a promising treatment for its high success rate, non-invasiveness, and low toxicity and side effects, effectively solving the challenges faced by traditional cancer treatment methods. The principle of PDT treatment is to activate PS from the ground state (S0) to the singlet excited state (S1) by absorbing near-infrared light of a specific wavelength through a photosensitizer (PS), and then undergo an intersystem jump to enter the triplet excited state (T1), generating cytotoxic reactive oxygen species (ROS), which ultimately leads to tumor cell death. Despite the rapid development of PDT, it has not yet been widely accepted as a first-line tumor treatment due to its shortcomings such as low penetration depth of light in tissues and non-negligible dark toxicity. More importantly, due to the complexity of the tumor microenvironment (TME), including abnormal physiological characteristics such as acidity, hypoxia, nutrient deprivation, metabolite accumulation, and imbalanced redox states, PDT cannot completely eradicate tumors. Therefore, it is urgent to explore cascade amplification anti-tumor strategies to optimize and enhance PDT strategies and improve tumor treatment effects. Although nanomaterials have high permeability and retention effect (EPR effect) in solid tumor areas, however, single EPR effect-driven nanodrug delivery has the disadvantages of insufficient accumulation and insufficient tumor retention. In order to solve these problems, the development of tumor microenvironment-activated nanoprobes with switching modes uses the characteristics of low pH and unbalanced redox state in the tumor microenvironment to activate imaging and therapeutic effects at the tumor site, while maintaining a "silent state" in non-tumor lesions, which is of great significance for the precise diagnosis and treatment of tumors. Therefore, the rational design of stimuli-responsive nanodrugs is crucial to improve the effective uptake of tumor cells and thus obtain excellent anti-tumor properties. Summary of the invention

[0004] In view of the problems of low treatment efficiency and lack of tumor targeting caused by the limitation of tumor microenvironment hypoxia when existing photosensitizers are used in the photodynamic therapy (PDT) process, the present invention provides an acidic tumor microenvironment activated nanoprobe and its synthesis method and application.

[0005] Therefore, targeting the acidic characteristics of the tumor microenvironment, it is necessary to explore Fe 2+ Starting from supramolecular nanoassembly, we selected the FDA-approved photosensitizer hematoporphyrin monomethyl ether (HMME), the anti-angiogenic drug thalidomide (Thal) and Fe 2+ As raw materials, a tumor microenvironment responsive activated nanoprobe was prepared. The probe achieved a low pH-driven cascade amplification of tumor therapeutic effects. The HMME in the nanoprobe exhibited good aggregation-induced singlet oxygen ( 1 O2) production capacity. As the material continues to accumulate in tumor tissue, the H + The J-aggregation structure is destroyed, causing disordered HMME stacking, leading to PDT shutdown. PDT treatment is driven by near-infrared (NIR) before the probe is degraded, and the Thal and Fe released after degradation 2+ The probes are used for chemotherapy and chemodynamic therapy (CDT), respectively, and the poor effect of single PDT treatment is solved. In addition, Fe 2+ Turn on the MRI signal to indicate the best time to give PDT laser irradiation. The dual-stage treatment before and after the probe degradation (first: PDT, second: CDT / chemotherapy) realizes the cascade expansion of tumor treatment strategy. This work proposes a self-assembled responsive nanoplatform constructed by endogenous components, which integrates MRI / PDT / CDT / chemotherapy and other functions. It has the characteristics of safety, low toxicity and side effects, and easy metabolism after degradation. It solves the problem of poor effect of single PDT treatment and provides a strategy for maximizing the tumor treatment efficacy of materials.

[0006] This material exhibits quenched MRI signals and good PDT effects under neutral conditions, and turns on MRI signals in the acidic environment of the tumor. It combines chemotherapy and CDT performance at the same time, and induces tumor cell ferroptosis and apoptosis through ROS-mediated oxidative stress, GSH consumption and GPX4 downregulation cascade photodynamic therapy, thereby achieving integrated tumor diagnosis and treatment.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions: An acidic tumor microenvironment activated nanoprobe, a nanoprobe HMME-Fe-Thal (HFT) constructed by self-assembly of iron ions, photosensitizer hematoporphyrin monomethyl ether HMME and thalidomide Thal.

[0008] Furthermore, the iron ions coordinated with the oxygen atoms in HMME and Thal formed a square bipyramidal geometry, and the adjacent secondary building units were stacked into three-dimensional supramolecular nanoparticles through hydrogen bonds and π–π interactions.

[0009] Further, the iron ion is Fe 2+ .

[0010] Furthermore, the particle size of the nanoprobe is 55-65 nm.

[0011] Furthermore, the loading efficiency of the chemotherapy drug thalidomide (Thal) was ≈68%.

[0012] A method for synthesizing an acidic tumor microenvironment activated nanoprobe comprises the following steps: Step 1, dissolving thalidomide (Thal) and hematoporphyrin monomethyl ether (HMME) in N,N-dimethylformamide (DMF), and vortexing to obtain a mixed solution; Step 2: slowly add ferrous chloride tetrahydrate aqueous solution (FeCl2·4H2O) to the mixed solution obtained in step 1, and vigorously stir the mixture at room temperature to react.

[0013] Step 3, ultrafiltration centrifugation and washing the product obtained in step 2 for several times to obtain HMME-Fe-Thal nanoparticles.

[0014] Furthermore, the mass ratio of thalidomide, hematoporphyrin monomethyl ether and ferrous chloride tetrahydrate is 2:1:10.

[0015] Furthermore, the volume ratio of the solvents used in steps 1 and 2 is 1:2.

[0016] Furthermore, the stirring speed in step 2 is 600 rpm / min~800 rpm / min, and the time is 2 min.

[0017] Furthermore, in step 3, the molecular weight cutoff of the ultrafiltration centrifugation is 30 kDa, the speed of the centrifugation is 2500 rpm, the time is 10 min, and the centrifugation is performed 3 times.

[0018] Application of an acidic tumor microenvironment-activated nanoprobe in magnetic resonance imaging.

[0019] Application of an acidic tumor microenvironment activated nanoprobe in photodynamic / chemodynamic / chemotherapeutic drug cascade amplification therapy for tumors.

[0020] Application of an acidic tumor microenvironment-activated nanoprobe in inducing ferroptosis of tumor cells.

[0021] Compared with the prior art, the present invention has the following advantages: The present invention self-assembles Fe 2+, anti-angiogenic drug thalidomide and photosensitizer HMME were used to prepare an acidic tumor microenvironment responsive smart nano-diagnostic probe. The obtained material showed a closed MRI signal and light-sensitive PDT efficacy before degradation at the tumor site. As the material continued to accumulate in the tumor tissue, under the stimulation of low pH in the tumor microenvironment, the MRI signal gradually turned on and released thalidomide, which could not only distinguish the cascade treatment process, but also enhance the PDT efficacy and amplify oxidative stress-induced tumor cell ferroptosis through the synergistic effect of CDT / chemotherapy / glutathione (GSH) consumption. This process preparation method is simple and efficient, and the obtained nanomaterials have the characteristics of safety, low toxicity and side effects, and easy metabolism after degradation, and have great prospects for clinical application in oncology. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is a transmission electron microscope image of the activated self-assembled nanoprobe synthesized in Example 1 of the present invention.

[0023] Figure 2 This is the ultraviolet spectrum of the activated self-assembled nanoprobe synthesized in Example 1 of the present invention.

[0024] Figure 3 This is a TEM image of the activated self-assembled nanoprobe synthesized in Example 1 of the present invention incubated under acidic conditions for 12 h.

[0025] Figure 4 This is the T1 relaxation signal of the activated self-assembled nanoprobe synthesized in Example 1 of the present invention under different acidic pH conditions.

[0026] Figure 5 This is the cumulative release curve of Thal of the activated self-assembled nanoprobe synthesized in Example 1 of the present invention under different acidic pH conditions.

[0027] Figure 6 This is a study on the change in reactive oxygen species produced over time after the activated self-assembled nanoprobe synthesized in Example 1 of the present invention is co-incubated with hydrogen peroxide at pH 6.5.

[0028] Figure 7 This is a study on the generation of singlet oxygen by the activated self-assembled nanoprobe synthesized in Example 1 of the present invention under near-infrared (NIR) laser irradiation: Figure (a) pH 7.4; Figure (b) pH 6.5.

[0029] Figure 8 This is a study on the time-dependent changes in GSH consumption of the activated self-assembled nanoprobe synthesized in Example 1 of the present invention.

[0030] Fig. 9This is a study on the cytotoxicity of CCK-8 of the activated self-assembled nanoprobe synthesized in Example 1 of the present invention under different treatment conditions.

[0031] Fig.10 Trypan blue staining images of the activated self-assembled nanoprobe synthesized in Example 1 of the present invention co-incubated with tumor cells under different treatment conditions.

[0032] Fig.11 Protein immunoblotting analysis of the activated self-assembled nanoprobe synthesized in Example 1 of the present invention inducing ferroptosis in tumor cells under different treatment conditions. Figure (a) shows the immunoblotting analysis of GPX4 under different treatment conditions, Figure (b) shows the change in the ratio of GSH / GSSG under different treatment conditions, and Figure (c) shows the content analysis of malondialdehyde (MDA) under different treatment conditions.

[0033] Fig.12 This is a study of the anti-tumor effect of the activated self-assembled nanoprobe synthesized in Example 1 of the present invention at the in vivo level. Figure (a) shows the change in the relative tumor volume of mice during treatment, Figure (b) shows the weight change of mice in each group after treatment, and Figure (c) shows the tumor photos of mice collected on the 14th day. DETAILED DESCRIPTION

[0034] In order to gain a deeper understanding of the present invention, we will provide a comprehensive and detailed description of the present invention. However, the present invention has multiple implementations and is not limited to the specific examples listed herein. The presentation of these examples is intended to deepen the comprehensive understanding of the disclosure of the present invention.

[0035] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0036] Thalidomide was purchased from MacLean Biochemical Technology Co., Ltd. (Shanghai, China), catalog number T911502-25 mg; hematoporphyrin monomethyl ether was purchased from Shanghai Yuanye Biotechnology Co., Ltd., catalog number S61821-100 mg; ferrous chloride tetrahydrate and N,N-dimethylformamide were purchased from Aladdin Biochemical Technology Co., Ltd. (Shanghai, China).

[0037] Example 1: Synthesis of HFT NPs Weigh 1 mg of thalidomide (Thal) and 0.5 mg of hematoporphyrin monomethyl ether (HMME), add 500 μL of N,N-dimethylformamide (DMF), and vortex for 1 min to obtain a mixed solution; Add 1 mL of 10 mg / mL ferrous chloride tetrahydrate (FeCl2·4H2O) aqueous solution to the mixed solution and stir vigorously for 1 min. After ultrafiltration centrifugation (2500 rpm, 10 min), the HMME-Fe-Thal nanoparticles (HFT NPs) were obtained and stored at 4 °C for further use.

[0038] Example 2: Characterization of HFT NPs The sample was dropped onto a 400-mesh copper grid covered with a carbon film, and after it dried naturally, it was observed under a transmission electron microscope. Figure 1 The figure shows a transmission electron microscope image of the self-assembled nanoprobe synthesized in Example 1 of the present invention. It can be seen from the figure that the synthesized nanoparticles have a uniform, monodisperse spherical morphology, a smooth surface, and a diameter of 55-65 nm.

[0039] Thalidomide (Thal), hematoporphyrin monomethyl ether (HMME) and HFT NPs samples were dissolved in aqueous solution, and the absorbance in the wavelength range of 200-800 nm was measured on a UV spectrophotometer. Figure 2 This is the UV spectroscopic spectrum of an acidic tumor microenvironment (TME) activated self-assembled nanoprobe for tumor cascade amplification therapy synthesized in Example 1 of the present invention. As can be seen from the figure, the synthesized HFT NPs show two characteristic peaks of HMME and Thal at 397 nm and 302 nm, respectively, indicating the successful synthesis of the nanoprobe.

[0040] Example 3: Performance study of HFT NPs HFT NPs were incubated with pH 6.5 phosphate buffer for 12 h, and the sample was dropped onto a 400-mesh copper grid covered with a carbon film. After it was dried naturally, the morphology of the sample was observed under an electron microscope. Figure 3 As shown, it is a TEM image of an acidic tumor microenvironment (TME) activated self-assembled nanoprobe for tumor cascade amplification therapy synthesized in Example 1 of the present invention incubated under acidic conditions of pH 6.5 for 12 h. Figure 3 It can be seen that the spherical morphology of HFT NPs is gradually destroyed and deformed into a colloidal structure, which indicates that the synthesized HFT NPs can disintegrate in response to acidic conditions.

[0041] After incubating HFT NPs with different concentrations in pH 6.5 and pH 5.5 phosphate buffer for 1 h, the nanoprobe magnetic resonance was detected. T 1 Relaxation rate. Figure 4 As shown, the acidic tumor microenvironment (TME) activated self-assembled nanoprobe for tumor cascade amplification therapy synthesized in Example 1 of the present invention has magnetic resonance images under different acidic pH conditions. T 1 Relaxation rate. Figure 4 It can be seen that with the decrease of pH, the r1 value of HFT NPs increases significantly, indicating that HFT NPs have low pH-activated MRI switch function.

[0042] The release behavior of HFT NPs in two acidic buffers, pH 6.5 and pH 5.5, was studied using dialysis bags. The cumulative release content of Thal was calculated by measuring the absorbance of Thal at 302 nm, and the cumulative release curve of Thal was plotted. Figure 5 As shown, it is the cumulative release curve of Thal under acidic pH conditions for a self-assembled nanoprobe activated by an acidic tumor microenvironment (TME) for tumor cascade amplification therapy synthesized in Example 1 of the present invention. It can be seen from the figure that after incubation for 12 h at pH 6.5, the release of Thal in HFT NPs reached 49%, while at pH 5.4, the release of Thal could reach 68%, indicating that HFT NPs have good pH-dependent degradable behavior, can be degraded in the acidic environment of the tumor, and release chemotherapy drugs to exert anti-tumor effects.

[0043] Methylene blue (MB) was added to a solution containing HFT and hydrogen peroxide (pH 6.5), which was then stirred in the dark for 10 min, and the generation of ·OH was evaluated by monitoring the absorbance intensity of MB at 664 nm. Figure 6 As shown in the figure, the acidic tumor microenvironment (TME) activated self-assembled nanoprobe for tumor cascade amplification therapy synthesized in Example 1 of the present invention is co-incubated with hydrogen peroxide at pH 6.5 to produce reactive oxygen species over time. It can be seen from the figure that the characteristic peak of MB gradually decreases under acidic conditions, which indicates that HFT NPs drive Fe 2+ Released, it undergoes Fenton reaction with hydrogen peroxide to produce ·OH.

[0044] Using DPBF as 1 O2 chemical probe to detect the O2 induced by 808 nm laser irradiation on HFT NPs 1 The production of O2. Figure 7 As shown in the figure, a self-assembled nanoprobe activated by acidic tumor microenvironment (TME) for tumor cascade amplification therapy synthesized in Example 1 of the present invention produces singlet oxygen under near-infrared laser irradiation. It can be seen from the figure that the laser irradiation duration is 20 min. Under neutral conditions, as the laser irradiation time increases, the absorbance of the characteristic absorption peak of DPBF at 410 nm gradually decreases from 1.8 to 1.1; under acidic conditions, the characteristic absorption peak of DPBF only decreases to 1.5, indicating that 1The generation of O2 was significantly suppressed, which was due to the fact that HMME in HFT NPs could be generated through J-aggregation under laser irradiation. 1 O2, however, under acidic conditions, H + The ions destroyed the J-aggregation structure of HMME in HFT NPs, resulting in the shutdown of PDT.

[0045] HFT NPs with different concentrations were co-incubated with GSH solution and hydrogen peroxide in a pH 6.5 buffer solution, and a certain amount of the mixture was taken at different time points to detect the glutathione consumption capacity of HFT NPs by using 5,5'-dithiomethyl(2-nitrobenzoic acid) (DTNB), as shown in Figure 8 As shown, the consumption of GSH changes over time by a self-assembled nanoprobe activated by an acidic tumor microenvironment (TME) for tumor cascade amplification therapy synthesized in Example 1 of the present invention. As can be seen from the figure, under acidic conditions, as the concentration of nanoparticles increases, the absorbance of DTNB at 412 nm decreases, that is, the concentration of GSH gradually decreases, indicating that HFT NPs have the ability to consume GSH.

[0046] Example 4: In vitro antitumor activity of HFT NPs Fig. 9 The cytotoxicity of the acidic tumor microenvironment (TME) activated self-assembled nanoprobe for tumor cascade amplification therapy synthesized in Example 1 of the present invention under different treatment conditions was studied. When the HFT NPs concentration reached 200 μg mL -1 When treated with HFT + 808 nm Laser, the cell viability was 82.73%, 44.09%, and 27.92% in the HFT group, HFT + 808 nm Laser, and HFT + pH 5.5, respectively. After treatment with HFT + pH 5.5 + H2O2, the cell viability decreased to 22.34%, indicating that HFT has the potential to be an effective therapeutic drug for killing cancer cells.

[0047] Figure 10 shows the trypan blue staining images of the acidic tumor microenvironment (TME) activated self-assembled nanoprobe for tumor cascade amplification therapy synthesized in Example 1 of the present invention co-incubated with tumor cells under different treatment conditions. The cells were treated according to different grouping conditions, and the dead cells were observed using trypan blue staining. Compared with the control group, some cells in the HFT + 808 nmLaser and HFT + pH 5.5 groups were observed to be stained blue. However, a large number of dead cells (blue cells) were observed in the cells treated with HFT + pH 5.5 + H2O2, which further illustrates the excellent in vitro anti-tumor effect of HFT NPs.

[0048] Study on the ferroptosis of tumor cells induced by nanoprobes under different treatment conditions The expression level of GPX4 under different treatment conditions was detected by Western blotting. Fig.11 As shown in FIG. 1 , it is a schematic diagram of the research results of a self-assembled nanoprobe activated by an acidic tumor microenvironment (TME) for tumor cascade amplification therapy synthesized in Example 1 of the present invention, which induces ferroptosis in tumor cells under different treatment conditions. Fig.11 As shown in (a), the expression of GPX4 in the pH 5.5 + hydrogen peroxide group was significantly downregulated, while that in the pH 6.5 + hydrogen peroxide group showed a slight downward trend; in addition, the levels of GSH and GSSG were determined using a GSH colorimetric detection kit, and the GSG / GSSH ratio was calculated. Fig.11 (b) The expression of GSG / GSSH in the pH 5.5 + hydrogen peroxide group was significantly downregulated, indicating that HFT NPs have a significant GSH consumption capacity, resulting in a decrease in intracellular GPX4 and inducing ferroptosis in tumor cells. Lipid peroxide accumulation is one of the basic characteristics of ferroptosis. The lipid peroxide content after treatment under different conditions was detected by using malondialdehyde (MDA), such as Fig.11 As shown in (c), the MDA content in the pH 5.5 + hydrogen peroxide group increased significantly, indicating that HFT NPs induced ferroptosis in tumor cells under this condition.

[0049] Example 5: In vivo antitumor activity of HFT NPs 4T1 cells were inoculated subcutaneously in the right thigh of nude mice to establish a 4T1 tumor-bearing mouse model. When the tumor volume reached 100 mm 3 The mice were randomly divided into 4 groups: (1) PBS group (as control); (2) HFT + V c (vitamin C) group (chemotherapy); (3) HFT group (CDT / chemotherapy); (4) HFT + L group (PDT / CDT / chemotherapy) were given corresponding treatments, and the body weight and tumor volume of the tested mice were recorded every other day. After 14 days, all tumor-bearing mice were killed, and the tumor tissues were isolated and photographed. Fig.12 As shown, the anti-tumor effect of a self-assembled nanoprobe activated by an acidic tumor microenvironment (TME) for tumor cascade amplification therapy synthesized in Example 1 of the present invention was studied at the in vivo level. Fig.12It can be seen that the tumor in the PBS group grew rapidly to 18.1 times the initial volume, while the tumor volume in the HFT + Vc group and the HFT group grew to 7.2 times and 7.6 times the initial volume, respectively. In contrast, the tumor volume of mice in the HFT + L group (PDT / CDT / chemotherapy) was only 2.9 times the initial volume, showing a strong tumor inhibition effect. There was no significant change in the weight of mice between the groups, confirming the good biosafety of HFT NPs.

[0050] The contents not described in detail in the specification of the present invention belong to the prior art known to the professional and technical personnel in the field. Although the illustrative specific embodiments of the present invention are described above to facilitate the understanding of the present invention by the technical personnel in the field, it should be clear that the present invention is not limited to the scope of the specific embodiments. For the ordinary technical personnel in the field, as long as various changes are within the spirit and scope of the present invention defined and determined by the attached claims, these changes are obvious, and all inventions and creations using the concept of the present invention are protected.

Claims

1. An acidic tumor microenvironment activated nanoprobe, Features: The nanoprobe HMME-Fe-Thal is constructed by self-assembly of iron ions, photosensitizer hematoporphyrin monomethyl ether HMME and thalidomide Thal.

2. The acidic tumor microenvironment activated nanoprobe according to claim 1, Features: The iron ions are coordinated with the oxygen atoms in HMME and Thal to form a square bipyramidal geometry, and the adjacent secondary building units are stacked into three-dimensional supramolecular nanoparticles through hydrogen bonds and π–π interactions.

3. The acidic tumor microenvironment activated nanoprobe according to any one of claims 1 or 2, Features: The iron ion is Fe 2+ .

4. The acidic tumor microenvironment activated nanoprobe according to any one of claims 1 or 2, Features: The particle size of the nanoprobe is 55-65 nm.

5. A method for synthesizing an acidic tumor microenvironment activated nanoprobe. It is characterized in that The following steps are involved: Step 1, dissolving thalidomide and hematoporphyrin monomethyl ether in N,N-dimethylformamide, and vortexing to obtain a mixed solution; Step 2, slowly adding an aqueous solution of ferrous chloride tetrahydrate to the mixed solution obtained in step 1, and vigorously stirring the mixture at room temperature to react; Step 3, ultrafiltration centrifugation and washing the product obtained in step 2 for several times to obtain HMME-Fe-Thal nanoparticles.

6. The method for synthesizing an acidic tumor microenvironment activated nanoprobe according to claim 5, Features: The mass ratio of thalidomide, hematoporphyrin monomethyl ether and ferrous chloride tetrahydrate is 2:1:10; the volume ratio of the solvents used in steps 1 and 2 is 1:

2.

7. The method for synthesizing an acidic tumor microenvironment activated nanoprobe according to claim 5, Features: The stirring speed in step 2 is 600 rpm / min~800 rpm / min, and the time is 2 min; the molecular weight cutoff of ultrafiltration centrifugation in step 3 is 30 kDa, the centrifugation speed is 2500 rpm, the time is 10 min, and centrifugation is performed 3 times.

8. Use of the acidic tumor microenvironment activated nanoprobe according to any one of claims 1 to 2 or the acidic tumor microenvironment activated nanoprobe synthesized by the synthesis method according to any one of claims 5 to 7 in magnetic resonance imaging.

9. Use of an acidic tumor microenvironment activated nanoprobe according to any one of claims 1 to 2 or an acidic tumor microenvironment activated nanoprobe synthesized by the synthesis method according to any one of claims 5 to 7 in synthesizing photodynamic / chemodynamic / chemotherapeutic drug cascade amplification tumor treatment products.

10. Use of an acidic tumor microenvironment activated nanoprobe according to any one of claims 1 to 2 or an acidic tumor microenvironment activated nanoprobe synthesized by the synthesis method according to any one of claims 5 to 7 in synthesizing products that induce tumor cell ferroptosis.

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