Preparation method and application of silica plastid for releasing carbon monoxide and chemotherapeutic drugs through ultrasonic / hydrogen peroxide dual response

Abstract

The invention relates to a multifunctional silica plastid integrating chemotherapy, immunotherapy and gas therapy, and relates to a preparation method of the multifunctional silica plastid and application of the multifunctional silica plastid in tumor diagnosis and treatment. The schematic diagram is as shown in the figure, the membrane components comprise conventional phospholipid and complex lipid, a chemotherapeutic drug doxorubicin (DOX) entrapped on a hydrophilic core and Fe3 (CO) 12 entrapped on a hydrophobic core, and the chemotherapeutic drug can be adjusted according to needs and is suitable for broad-spectrum tumor treatment. The drug-loaded silica plastid can generate part of carbon monoxide in a tumor high-concentration hydrogen peroxide (H2O2) environment and release internally-loaded chemotherapeutic drugs. Under the action of ultrasound (US), the multifunctional silicon plastid can realize fixed-point release of chemotherapeutic drugs DOX and carbon monoxide at a tumor site, the enrichment and uptake of the drugs at the tumor site are greatly improved, in addition, the system is combined with the alphaPD-L1 antibody, the immunosuppressive PD-L1 / PD-1 axis can be blocked, T cells are recruited to attack tumors, meanwhile, the immunosuppressive regulatory T cells (Tregs) are reduced, and the tumor treatment effect is improved. The tumor inhibition can be enhanced; the pulmonary metastasis can be obviously reduced.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical materials, and specifically relates to a multifunctional siliceous body integrating chemotherapy / gas therapy / immunotherapy, and its use in tumor diagnosis and treatment. Background Art

[0002] Malignant tumors are major diseases that threaten human health. Although chemotherapy is still an effective treatment for many tumors, it has problems such as low selectivity and high toxicity to healthy tissues. Liposome drugs can improve the pharmacokinetics and in vivo distribution of chemotherapeutic drugs with excellent biocompatibility, becoming a highly promising carrier for tumor chemotherapy. Approved preparations such as Abraxane, Marqibo, Doxil and DaunoXome have fully demonstrated the clinical application value of liposomes. However, traditional liposome drugs have the defect of insufficient stability, which causes the drug to leak prematurely before reaching the target, causing adverse reactions. Therefore, researchers have developed ceratosomes, whose surface polyorganosiloxane layer significantly improves the morphological stability and enhances the biocompatibility of the carrier by combining the advantages of liposomes and silica nanoparticles, effectively preventing premature drug release and improving targeted delivery. However, stable ceratosomes lack a suitable triggering mechanism, which limits drug release, may lead to insufficient therapeutic concentrations and induce tumor resistance. Therefore, giving ceratosomes stimulus-responsive properties to achieve precise drug release at the tumor site is of great significance for improving efficacy and reducing side effects.

[0003] Stimuli-responsive nanoplatforms are expected to achieve precise drug release, and are mainly divided into endogenous and exogenous response systems. Endogenous stimuli rely on specific pH, enzymes, redox and other conditions in the tumor microenvironment to trigger drug release, but there are problems such as large individual differences and strong tumor heterogeneity, resulting in uneven and uncontrollable drug release. Exogenous stimuli such as light, heat, magnetic fields, and ultrasound have better sensitivity, but are limited by tissue penetration depth, positioning accuracy or parameter safety. Therefore, a multi-responsive platform that combines endogenous and exogenous stimuli can effectively improve the selectivity and sensitivity of drug release.

[0004] Carbon monoxide (CO) is considered a "silent killer" due to its strong affinity with hemoglobin (Hb), which can cause severe hypoxia in important organs such as cardiovascular and cerebrovascular organs. Recent studies have found that CO has a concentration-dependent dual effect in tumor treatment: low concentrations of CO may promote tumor growth, while high concentrations of CO can target mitochondria, enhance reactive oxygen species (ROS) production and induce mitochondrial dysfunction, ultimately triggering tumor cell apoptosis. At the same time, CO can significantly enhance chemotherapy sensitivity by amplifying the toxic effects of cancer cells and protecting normal cells from chemotherapy damage. In addition, CO can also regulate immune responses and synergize with immunotherapy to improve the overall efficacy.

[0005] It is crucial to accurately deliver high-concentration CO to the tumor site and avoid Hb-related toxicity. Transition metal carbonyl compounds (CORMs) can act as CO donors and respond to high-concentration H in tumors through a Fenton-like reaction. 2 O 2 Encapsulating CORMs in highly stable carriers can improve delivery efficiency, reduce circulation leakage, and promote rapid release at the tumor site. 2 O 2 The reaction rate with CORMs is slow, making it difficult to quickly reach therapeutic concentrations and may even promote tumor growth. Therefore, there is an urgent need to develop more efficient release strategies.

[0006] Based on the above considerations, we developed a silicic body that releases carbon monoxide and chemotherapeutic drugs in dual response to ultrasound / hydrogen peroxide. 3 (CO) 12 As a CO prodrug, the active drug loading method was used to load doxorubicin (DOX) to construct a cascade system for synergistic anti-tumor therapy. The silicosome can effectively encapsulate DOX and Fe 3 (CO) 12 , preventing circulation leakage and reducing toxic side effects. After reaching the tumor site, Fe 3 (CO) 12 The abundant H 2 O 2 The reaction generates CO, and ultrasound irradiation can significantly accelerate the process, which not only enhances CO generation, but also regulates the tumor microenvironment by disrupting mitochondrial energy metabolism. CO promotes the formation of membrane pores on the surface of silicone, which promotes the rapid release of DOX and forms a synergistic anti-tumor effect with CO treatment. This system provides a new strategy for the efficient treatment of clinical tumors by precisely regulating the release of multiple drugs in time and space, combining the synergistic effect of CO and DOX and enhancing the efficacy of the immune checkpoint inhibitor αPD-L1 antibody. Summary of the invention

[0007] The purpose of the present invention is to provide a method for preparing a siliceous body capable of releasing carbon monoxide and chemotherapeutic drugs in a dual response to ultrasound / hydrogen peroxide.

[0008] Another object of the present invention is to provide an ultrasound / hydrogen peroxide dual-response silicic body that releases carbon monoxide and chemotherapeutic drugs for use in tumor diagnosis and treatment.

[0009] The structure of the siliceous body for releasing carbon monoxide and chemotherapeutic drugs in dual response to ultrasound / hydrogen peroxide of the present invention is shown in the attached figure. Figure 1 shown.

[0010] The present invention discloses a siliceous body that releases carbon monoxide and chemotherapeutic drugs in dual response to ultrasound / hydrogen peroxide, and the composition thereof comprises a composite lipid (CFL), a phospholipid (DSPC), DSPE-PEG2000, DOX and Fe 3 (CO) 12 , various phospholipids, complex lipids and CO prodrug Fe 3 (CO) 12 They can be self-assembled together in aqueous solution to form nanoparticles, and then the chemotherapy drug doxorubicin (DOX) can be encapsulated in the hydrophilic region by the ammonium bicarbonate active drug loading method.

[0011] The chemical structural formula of the composite lipid CFL is as follows:

[0012] The phospholipids are selected from the group consisting of 12 to 24 carbon chain lengths and include phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid and phosphatidylglycerol, specifically including 1,2-distearoyl-sn-glyceryl-3-phosphocholine (DSPC), 1,2-dipalmitoyl-sn-glyceryl-3-phosphatidylcholine (DPPC), 1,2-dipalmitoyl-sn-glyceryl-3-phosphatidic acid (DPPA), and distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000).

[0013] The chemotherapy drugs are characterized by various small molecule hydrophilic chemotherapy drugs, such as doxorubicin hydrochloride, cyclophosphamide, etc.

[0014] The method for preparing a siliceous body capable of releasing carbon monoxide and chemotherapeutic drugs in dual response to ultrasound / hydrogen peroxide of the present invention comprises the following steps:

[0015] 1) A certain proportion of CFL, DSPC and DSPE-PEG2000 were dissolved in ethanol, Fe 3 (CO) 12 Dissolve in tetrahydrofuran, then mix the organic solution evenly.

[0016] 2) The mixed system was injected into a 270 mM ammonium carbonate aqueous solution at a rotation speed of 900 rpm by injection method, and stirred for 10 minutes to obtain nanoparticles.

[0017] 3) The obtained system 2) was dialyzed in physiological saline at room temperature for 1 to 2 hours using a dialysis bag of 8000 to 14000 KD.

[0018] The system obtained above was transferred to a centrifuge tube, and a certain proportion of DOX (DOX / nanoparticle mass ratio 0-20%) was added, incubated in a 40°C water bath for 30 minutes, and then incubated in a 37°C shaking incubator overnight.

[0019] 4) The obtained system 3) was dialyzed in physiological saline at room temperature for 2-4 hours using a dialysis bag of 8000-14000 KD to remove the unencapsulated DOX.

[0020] 5) The system obtained above is transferred to a centrifuge tube to obtain a siliceous body that releases carbon monoxide and chemotherapeutic drugs in dual response to ultrasound / hydrogen peroxide.

[0021] The present invention describes a siliceous body that releases carbon monoxide and chemotherapeutic drugs in a dual response to ultrasound / hydrogen peroxide. The system encapsulates Fe by hydrophobic interaction. 3 (CO) 12 As a CO prodrug, the active drug loading method was used to load doxorubicin (DOX) to construct a cascade system for synergistic anti-tumor therapy. The silicosome can effectively encapsulate DOX and Fe 3 (CO) 12 , preventing circulation leakage and reducing toxic side effects. After reaching the tumor site, Fe 3 (CO) 12 The abundant H 2 O 2 The reaction generates CO, and ultrasound irradiation can significantly accelerate the process, which not only enhances CO generation, but also regulates the tumor microenvironment by disrupting mitochondrial energy metabolism. CO promotes the formation of membrane pores on the surface of silicone, which promotes the rapid release of DOX and forms a synergistic anti-tumor effect with CO treatment. This system provides a new strategy for the efficient treatment of clinical tumors by precisely regulating the release of multiple drugs in time and space, combining the synergistic effect of CO and DOX and enhancing the efficacy of the immune checkpoint inhibitor αPD-L1 antibody. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 It is a structural diagram of the siliceous body for releasing carbon monoxide and chemotherapeutic drugs in dual response to ultrasound / hydrogen peroxide described in the present invention; Figure 2 The particle size distribution diagram and electron microscope diagram of the multifunctional siliceous body prepared in specific embodiment 1; Figure 3 is an ultraviolet spectrum of hemoglobin after the multifunctional siliceous body produces carbon monoxide in specific embodiment 2; Figure 4 is an in vitro ultrasound contrast imaging image of the multifunctional siliceous body in specific embodiment 2; Figure 5 is the drug release curve of DOX in specific embodiment 3; Figure 6 is a laser confocal image of the multifunctional siliceous body taken up by tumor cells in specific example 4; Figure 7 is an image of fluorescence imaging of the multifunctional siliceous body at the animal tumor tissue in specific embodiment 5; Figure 8 is the animal tumor growth curve after the multifunctional siliceous body in specific embodiment 6 was used for chemotherapy / gas therapy / immunotherapy combined therapy; Fig. 9is the animal tumor growth curve after the multifunctional silicone combined with αPD-L1 therapy in specific example 7; Fig.10 is a diagram showing the effect of multifunctional siliceous bodies on tumor immunotherapy in specific embodiment 7; Fig.11 This is a graph showing the results of the multifunctional siliceous body inhibiting lung metastasis in specific example 7. DETAILED DESCRIPTION

[0023] The following specific embodiments will help to understand the present invention, but will not limit the contents of the present invention.

[0024] Example 1

[0025] Multifunctional silicosomes were prepared by ethanol injection method, and doxorubicin (DOX) loading was carried out by ammonium bicarbonate active drug loading technology. Specifically, CFL, DSPC and DSPE-PEG2000 were mixed in a molar ratio of 50:40:10, and the above lipid mixture was dissolved in ethanol. 3 (CO) 12 Dissolved in tetrahydrofuran, then injected with 270mM ammonium bicarbonate aqueous solution under 900rpm magnetic stirring to form nanoparticles. Subsequently, a dialysis bag (MWCO 8000-14000) was used for dialysis at room temperature for 1 hour to remove the organic solvent and ammonium bicarbonate, forming an ammonium bicarbonate concentration gradient inside and outside the particles. DOX aqueous solution was added to the nanoparticle suspension at a mass ratio of 1:20 to 1:10, incubated in a 40°C water bath for 30 minutes, and DOX loading was achieved through a transmembrane ammonium bicarbonate gradient. The nanoparticles were then incubated in a 37°C shaker for 12 hours to promote the formation of a silicate network on the surface of the siliceous body. Centrifuged at 2000r / min for 5 minutes to remove unencapsulated Fe 3 (CO) 12 After purification, the ultrasound / hydrogen peroxide dual-responsive silicoids (named as multifunctional silicoids DF@LCs) were obtained to release carbon monoxide and chemotherapeutic drugs (see Appendix Figure 1 ). As attached Figure 2 Shown is an electron microscope image of the ultrasound / hydrogen peroxide dual response siliceous body releasing carbon monoxide and chemotherapeutic drugs described in the present invention. The nanoparticles are spherical and about 50 nm in size.

[0026] Example 2

[0027] Detection of CO release from siliceous bodies by hemoglobin: 1 mL of multifunctional siliceous bodies (Fe 3 (CO) 12 :50mg / mL) and an EP tube containing 1mL of hemoglobin solution (1mg / mL) were placed in a vial, and sodium dithionite (SDT, 2mg) was added to reduce hemoglobin under nitrogen filling conditions, and the vial was quickly sealed. Ultrasonic (1.0MHz, 50% duty cycle, 1W / cm 2After treatment with 5% NH 2 O (100 μg / mL) for 10 min, the ultraviolet absorption peak at 350-650 nm was measured. 2 O 2 Or US treatment causes the hemoglobin absorption peak to blue shift from 430nm to 410nm (Appendix Figure 3 ), confirming that CO binds to hemoglobin.

[0026] The multifunctional siliceous body obtained in Example 1 was mixed with physiological saline in a volume ratio of 1:9 and then injected into a latex tube. 500 mL of ultrasonic degassed water was placed in a water tank, and the latex tube was placed in the middle of the liquid. The ultrasound diagnostic instrument contrast mode, MI: 0.06 (mechanical index), probe frequency: 3-12MHz, was used to observe the in vitro ultrasound contrast effect of the particles. The in vitro ultrasound contrast images are shown in the attached Figure 4 As shown in Figure 2, no ultrasound imaging signal was observed in the untreated DF@LCs. 2 O 2 When pretreated or irradiated with ultrasound, significant ultrasound imaging signals were detected, indicating the generation of CO gas. 2 O 2 Stronger ultrasound (US) imaging signals were observed when pre-treated with and US irradiation, indicating that more CO gas was produced.

[0028] Example 3

[0029] Evaluation of DOX release in vitro 1 mL of multifunctional silicosomes (1 mg / mL) was placed in PBS (pH 7.4) containing 0.1% Tween 80. 2 O 2 The concentrations were 0, 0.1, 1, and 5 mM, respectively, and the samples were shaken at 37°C (120 rpm). Ultrasonic parameters were 1.0 MHz, 50% duty cycle, 1 W / cm 2 The treatment was repeated 3 times. Samples were taken at regular intervals and the cumulative release rate of DOX was measured by a fluorescence spectrophotometer (excitation 480 nm, emission 590 nm). The DOX release curve is shown in the attached figure. Figure 5 As shown, no H 2 O 2 About 20% of DOX was released within 24 hours; at 5 mM 2 O 2 The release amount increased to 48% under H 2 O 2 Under the environment, after three consecutive US treatments, the release of DOX increased significantly, indicating that H 2 O 2 It can significantly accelerate the drug release process in synergy with US.

[0030] Example 4

[0031] In order to trace the uptake of multifunctional silica by tumor cells, DF@LCs were labeled with DSPE-Cy5.5, the nucleus was stained with Hoechst 33342, and the cell uptake at different time points was observed using a confocal microscope. The specific results are shown in the attached Figure 6 As shown, 488nm excitation light was used and red fluorescence at 600-750nm was collected. As a small molecule drug, free DOX diffused rapidly into the cell nucleus within 5 hours; while DOX encapsulated in DF@LCs showed only weak fluorescence due to the aggregation quenching effect. As the incubation time increased, the fluorescence intensity slightly increased, indicating that the cellular uptake of DF@LCs increased, but the released DOX was mainly retained in the cytoplasm, suggesting that it only depends on H 2 O 2 The release rate of H was slower. After the initial 4-hour incubation, the fluorescence intensity was significantly enhanced by applying US for 5 minutes, because ultrasound accelerated the release of H 2 O 2 The reaction with DF@LCs promoted the rapid generation of CO and triggered the release of DOX. When the incubation was further extended to 8 hours, DOX fluorescence was not only present in the cytoplasm, but also distributed in the nucleus, indicating that DOX molecules gradually migrated into the nucleus during the incubation process. This result highlights the key role of ultrasound in accelerating drug release.

[0032] Example 5

[0033] In order to evaluate the distribution of multifunctional silica bodies in vivo, silica bodies were labeled with DSPE-Cy5.5 and subjected to in vivo near-infrared fluorescence imaging. First, a mouse subcutaneous MCF-7 tumor model was established, and silica bodies (DF@LCs) and control group liposomes (DF@Ls) were injected into mice through the tail vein. Then, near-infrared fluorescence imaging of mice was performed at 1h, 2h, 4h, 8h, 12h, 24h, 48h and 72h. After 72 hours, the mice were dissected and the heart, liver, spleen, lung, kidney and tumor tissues were collected for fluorescence imaging (see Appendix). Figure 7 ), quantitative analysis showed that the tumor fluorescence in the DF@LCs group reached a peak at 4 hours and only slightly decayed by 12 hours. Even after 72 hours of injection, the tumor fluorescence intensity was only attenuated by 50%, indicating that it has continuous accumulation and retention characteristics in tumor tissues. In comparison, although the DF@Ls group showed a similar tumor enrichment trend, the fluorescence intensity at the tumor site at each time point was significantly weaker than that of the DF@LCs group. Because DF@LCs are organic-inorganic composite nanoparticles with a silicate network structure on the surface, their rigid structure helps maintain dimensional stability and avoid disintegration in the circulation, so they can be retained in the tumor site for a longer period of time.

[0034] After 72 hours, the mice were dissected and the heart, liver, spleen, lung, kidney and tumor tissues were collected for fluorescence imaging. Quantitative analysis showed that the Cy5.5 and DOX fluorescence intensities of the tumors in the DF@LCs group were significantly higher than those in the DF@Ls group. This proves that DF@LCs can not only effectively enrich in the tumor site, but also have good retention ability, which has positive significance for tumor treatment (Appendix Figure 7 ).

[0035] Example 6

[0036] In vivo treatment experiments investigated whether the prepared multifunctional silicosomes could effectively inhibit tumor growth. MCF-7 tumor-bearing BALB / c nude mice were randomly divided into 7 groups, namely PBS group, ultrasound alone group, D@Ls group, D@LCs group, F@LCs+US group, DF@LCs group and DF@LCs+US group. The drug administration method was tail vein injection, with DOX dose of 2 mg / kg and Fe 3 (CO) 12 The dose was 4.3 mg / kg. For the group receiving ultrasound treatment, the application parameters were 1 MHz, 1.5 W / cm 2 , 20% duty cycle ultrasound irradiation for 5 minutes. The tumor volume and body weight of the mice were recorded every two days for 16 consecutive days. (Tumor volume = 1 / 2 × length × width 2 ). The results showed that the D@Ls group showed partial tumor inhibition, while the DF@LCs+US group showed significant tumor growth inhibition, which was due to the synergistic effect of ultrasound-enhanced CO gas therapy and chemotherapy. 3 (CO) 12 H 2 O 2 The reaction produced a large amount of CO gas, which not only caused mitochondrial dysfunction, but also promoted the rapid release of DOX from DF@LCs, thereby optimizing the combined treatment effect. However, its therapeutic effect was significantly weaker than that of the D@LCs group, and the F@LCs+US group and the DF@LCs group had more obvious therapeutic effects. Figure 8 shown.

[0037] Example 7

[0038] Test of tumor immune effect. A 4T1 mouse breast cancer model was constructed to explore the therapeutic potential of DF@LCs combined with programmed death ligand 1 (PD-L1) antibody (αPD-L1). In this experiment, mice received three cycles of drug treatment and two administrations of αPD-L1 (see figure). The results are shown in the attached figure. Fig. 9As shown in the results, compared with the PBS control group, αPD-L1 monotherapy did show a moderate tumor growth inhibition effect, while the combined treatment of DF@LCs, ultrasound and αPD-L1 produced an extremely strong anti-tumor response.

[0039] The infiltration of lymphocyte subsets in the tumor microenvironment was further evaluated by flow cytometry. The results showed that compared with the PBS group, αPD-L1 treatment significantly increased the infiltration of CD4+ helper T cells and CD8+ cytotoxic T cells, while reducing the infiltration of regulatory T cells (Tregs), a phenomenon usually associated with anti-tumor immune recovery. When DF@LCs, ultrasound and αPD-L1 were combined, the infiltration of CD4+ and CD8+ T cells in the tumor microenvironment reached the highest level, while Tregs cells dropped to the lowest level, indicating strong immune activation (see Appendix). Fig.10 ).

[0036] After the treatment, the inhibition of tumor metastasis was detected. The PBS group had the largest number of nodules, which may be due to the uncontrolled growth of the untreated tumor. The number of nodules in the DF@LCs or αPD-L1 monotherapy groups decreased, among which DF@LCs directly killed tumor cells through chemotherapy, while αPD-L1 restarted the anti-tumor immune response through immune checkpoint blockade. DF@LCs combined with ultrasound therapy further significantly reduced lung metastasis, which may be due to the combined effect of CO and chemotherapy triggering a strong immune response against dying tumor cells. There were almost no lung nodules in the DF@LCs, ultrasound and αPD-L1 triple therapy group, indicating that the combination therapy triggered an efficient immune response and significantly inhibited tumor lung metastasis (Appendix Fig.11 ). The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A siliceous body that releases carbon monoxide (CO) and chemotherapeutic drugs in a dual response to ultrasound / hydrogen peroxide, characterized in that The shell of the particle is composed of complex lipids (CFL), phospholipids (DSPC) and DSPE-PEG2000; various phospholipids, complex lipids and CO prodrug Fe3(CO) 12 They can be self-assembled together in aqueous solution to form nanoparticles, and the chemotherapeutic drug doxorubicin (DOX) can be encapsulated in the hydrophilic region by the ammonium bicarbonate active drug loading method. The system can trigger CO generation and DOX release by H2O2 and ultrasound (US).

2. According to claim 1, the siliceous body that releases carbon monoxide (CO) and chemotherapeutic drugs in a dual response to ultrasound / hydrogen peroxide, the chemical structural formula of the composite lipid is as follows:

3. The siliceous body for releasing carbon monoxide (CO) and chemotherapeutic drugs by ultrasound / hydrogen peroxide dual response according to claim 1, characterized in that CO can be generated under the triggering of high concentration H2O2 or US, and the particle size of the nanoparticles ranges from 20 to 200 nm.

4. The method for preparing a siliceous body capable of releasing carbon monoxide (CO) and chemotherapeutic drugs in a dual response to ultrasound / hydrogen peroxide according to claim 1, comprising the following steps: 1) A certain proportion of CFL, DSPC and DSPE-PEG2000 were dissolved in ethanol, Fe3(CO) 12 Dissolve in tetrahydrofuran, then mix the organic solution evenly; 2) injecting the mixed system into a 270 mM ammonium carbonate aqueous solution at a speed of 900 rpm, stirring for 10 minutes, to obtain nanoparticles; 3) using a 8000-14000KD dialysis bag to dialyze the obtained system 2) in physiological saline at room temperature for 1-2 hours; transferring the obtained system to a centrifuge tube, adding a certain proportion of DOX (DOX / nanoparticle mass ratio 0-20%), incubating in a 40°C water bath for 30 minutes, and then incubating in a 37°C shaker overnight; 4) dialyzing the obtained system 3) in physiological saline at room temperature for 2-4 h using a dialysis bag of 8000-14000 KD to remove unencapsulated DOX; 5) The system obtained above is transferred to a centrifuge tube to obtain a siliceous body that releases carbon monoxide in dual response to ultrasound / hydrogen peroxide.

5. The siliceous body for releasing carbon monoxide (CO) and chemotherapeutic drugs by ultrasound / hydrogen peroxide dual response according to claim 1, characterized in that The phospholipids in the components are selected from carbon chain lengths of 12 to 24 carbons and include phosphatidylcholine, phosphatidylethanolamine, phosphatidic acid and phosphatidylglycerol, specifically including 1,2-distearoyl-sn-glyceryl-3-phosphocholine (DSPC), 1,2-dipalmitoyl-sn-glyceryl-3-phosphatidylcholine (DPPC), 1,2-dipalmitoyl-sn-glyceryl-3-phosphatidic acid (DPPA), and distearoylphosphatidylethanolamine-polyethylene glycol 2000 (DSPE-PEG2000).

6. The siliceous body for releasing carbon monoxide (CO) and chemotherapeutic drugs by ultrasound / hydrogen peroxide dual response according to claim 1, characterized in that The siliceous body can be used for the diagnosis and treatment of tumors.

Images