TW201711674A - Carriers and uses thereof - Google Patents

Abstract

Use of a carrier is provided. The use is for the preparation of a drug for treating a cancer. The carrier comprises an aqueous phase inner core including a hydrogen peroxide (H2O2); and an oil phase outer shell layer covering the aqueous phase inner core. The oil phase outer shell layer includes a metal ion provider and a polymer compound, wherein when the hydrogen peroxide contacts the metal ion provider, the hydrogen peroxide and a metal ion provided by the metal ion provider produce a Fenton reaction and generate a reactive oxygen species (ROS). In addition, use of another carrier is provided. The use is for the preparation of a drug for treating the cardiovascular diseases. The carrier comprises an aqueous phase inner core including the S-nitrosothiols (RSNO); and an oil phase outer shell layer covering the aqueous phase inner core. The oil phase outer shell layer includes a catalyst, wherein when the S-nitrosothiols contacts the catalyst, the S-nitrosothiols and the catalyst produce a catalytic reaction and generate a nitric oxide (NO).

Description

Carrier and its use

The present invention relates to a carrier and its use, and more particularly to a carrier comprising a hydrophilic core and a hydrophobic outer shell and uses thereof.

Recent advances in micro or nano carriers have created many unprecedented opportunities in the life sciences. In particular, there has been a great breakthrough in the development of various micro or nano carriers with a wide range of functions. The ability to develop the intrinsic and extrinsic properties of micro or nano carriers further creates a novel therapeutic/diagnostic (therapeutic diagnostics) application of micro or nano carriers in vivo, on the basis of which a better understanding of human disease can be achieved. And treatment. Therefore, how to formulate the intrinsic and extrinsic characteristics of micron or nano carriers to effectively use them in the diagnosis and treatment of diseases is an important issue in the field of life sciences.

Ultrasound (US) is widely used in the diagnosis of diseases due to its low cost, safe use, painless operation, easy access and non-invasive imaging. Ultrasonic images can be enhanced by using micron or nanocarriers as ultrasonic contrast agents. Micron or nanocarriers used as ultrasonic contrast agents are typically filled with perfluorocarbons or nitrogen.

In the treatment of diseases, taking cancer as an example, in recent years, micron or nano carriers are often used to carry anticancer drugs into the body. However, the current role of micro or nano carriers is only a single Pure delivery of anticancer drugs has no real benefit for the efficacy of anticancer drugs.

In addition, cardiovascular and cerebrovascular diseases are the number one cause of death worldwide. Previous studies have attributed the high mortality of these important diseases to ischemia-reperfusion (I/R) damage. Nitric oxide (NO), a key mediator in the cardiovascular and cerebrovascular system, is thought to have the potential to inhibit I/R damage due to its vasodilation and anti-apoptotic activity. Further, low concentrations of NO can avoid apoptosis induced by trophic factor withdrawal, Fas, tumor necrosis factor alpha (TNFα), and lipopolysaccharide. Its anti-apoptotic mechanism can be characterized by the expression of protective genes such as heat shock protein and B cell lymphoma-2 (Bcl-2) and cysteine thiol (S-nitrosylation). Direct inhibition of apoptotic caspase family proteases to achieve anti-apoptotic effects. However, the clinical application of NO in cardiovascular and cerebrovascular diseases is mainly limited to acute myocardial infarction, in part due to the difficulty of controlling such structurally simple but chemically complex molecules in many aspects of the body. It is necessary to develop strategies to control the dose of NO and its timing, duration and location in complex physiological environments, as such development not only promotes our understanding of the therapeutic activity of NO, but also extends NO in other important hearts. Clinical application of cerebrovascular diseases.

The first aspect of the present invention provides a use of a carrier for the preparation of a medicament for treating a cancer, wherein the carrier comprises: a hydrophilic core comprising a hydrogen peroxide (H ₂ O ₂ ); and a hydrophobicity An outer shell encasing the hydrophilic core and comprising a metal ion donor and a polymer compound, wherein: when the hydrogen peroxide is in contact with the metal ion donor, the hydrogen peroxide and the metal ion donor Providing one of the metal ions produces a Fenton reaction to form a reactive oxygen species (ROS).

The second aspect of the present invention provides a use of a carrier for the preparation of a medicament for treating a cardiovascular disease, wherein the carrier comprises: a hydrophilic core comprising an S-nitrosothiols (RSNO) a hydrophobic outer shell encapsulating the hydrophilic core and comprising a catalyst, wherein: when the S-nitrosothiol is contacted with the catalyst, a catalytic reaction is generated to form nitric oxide , NO).

The third aspect of the present invention provides a use of a carrier for preparing a medicament for treating a disease, wherein the carrier comprises: a hydrophilic core comprising a compound; and a hydrophobic outer shell encapsulating the hydrophilic core And comprising a metal nanoparticle and an amphoteric compound, wherein: when the compound is in contact with the metal nanoparticle, a chemical reaction is generated to form a functional product.

The fourth aspect of the present invention provides a carrier comprising: a hydrophilic core comprising a substance; a hydrophobic outer shell encapsulating the hydrophilic core, and comprising a nanoparticle and an amphiphilic compound, wherein: When a substance reacts with the nanoparticle to produce a chemical reaction, a functional product is formed.

10, 20, 30, 40 ‧ ‧ carriers

101, 201, 301, 401‧‧ ‧ hydrophilic core

102, 202, 302, 402‧‧‧ hydrophobic shell

103‧‧‧ Hydrogen peroxide

104‧‧‧Metal ion donor

105, 205‧‧‧ polymer compound

106‧‧‧Reactive oxygen species

107‧‧‧ Stabilizer

108‧‧‧ positively charged molecules

203‧‧‧S-nitrosothiol

204‧‧‧ Catalyst

206‧‧‧ Nitric oxide

303‧‧‧ compounds

304‧‧‧Metal Nanoparticles

305‧‧‧Amphiphilic compounds

306, 406‧‧‧ functional products

403‧‧‧ substances

404‧‧‧Nano particles

405‧‧‧Amphiphilic compounds

The first figure shows the carrier of the first embodiment of the present invention.

The second figure shows the carrier of the first embodiment of the present invention.

The third figure shows the carrier of the second embodiment of the present invention.

The fourth figure shows the carrier of the third embodiment of the present invention.

The fifth figure shows the carrier of the fourth embodiment of the present invention.

FIG sixth (a) shows triiron tetraoxide present invention (Fe ₃ O ₄₎ - polylactic glycolic acid (poly (lactic-co-glycolic acid), PLGA) low-resolution transmission electron microscope image of the carrier .

Figure 6 (b) shows a high magnification transmission electron microscope image of the Fe ₃ O ₄ -PLGA carrier of the present invention.

Figure 6 (c) shows a low resolution transmission electron microscope image of the H ₂ O ₂ /Fe ₃ O ₄ -PLGA carrier of the present invention.

Figure 6 (d) shows a high magnification transmission electron microscope image of the H ₂ O ₂ /Fe ₃ O ₄ -PLGA carrier of the present invention.

Figure 6 (c) shows a low resolution transmission electron microscope image of the H ₂ O ₂ /Fe ₃ O ₄ -PLGA carrier of the present invention.

Figure 6 (d) shows a high magnification transmission electron microscope image of the H ₂ O ₂ /Fe ₃ O ₄ -PLGA carrier of the present invention.

Fig. 6(e) shows a transmission electron microscope image of the H ₂ O ₂ /Fe ₃ O ₄ -PLGA carrier infused with 200 μL of hydrogen peroxide of the present invention.

Figure 6 (f) shows a transmission electron microscope image of H ₂ O ₂ /Fe ₃ O ₄ -PLGA infused with 400 μL of hydrogen peroxide carrier of the present invention.

Figure 7 (a) shows the calibration curve of the colormetric test of the H ₂ O ₂ /Fe ₃ O ₄ -PLGA carrier of the present invention.

Figure 7 (b) shows a comparison of different concentrations of hydrogen peroxide in the colorimetric assay of the H ₂ O ₂ /Fe ₃ O ₄ -PLGA carrier of the present invention.

The eighth panel shows the safety evaluation of the H ₂ O ₂ (600 μL)/Fe ₃ O ₄ -PLGA and Fe ₃ O ₄ -PLGA carriers of the present invention.

The ninth panel shows the stability evaluation of the H ₂ O ₂ (600 μL)/Fe 3 O4-PLGA carrier of the present invention in phosphate buffered saline (PBS) (pH 5).

The tenth graph shows the micro-ultrasonic-triggered H ₂ O ₂ /Fe3O4-PLGA carrier disintegration of the present invention.

Figure 11 shows the reaction of the carrier of the present invention with Ru(dpp) ₃ Cl ₂ .

Figure 12 shows the acoustic properties of the carrier of the invention in vitro on an agar gel model.

The thirteenth chart shows the reaction of the Fe ₃ O ₄ nanoparticles of the present invention and H ₂ O ₂ .

Figure 14 shows the relationship between the ultrasonic irradiation time of the H ₂ O ₂ /Fe3O4-PLGA carrier of the present invention and the yield of reactive oxygen species.

The fifteenth graph shows the results of an animal experiment in which the acoustic properties of the H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA carrier of the present invention were produced.

Figure 16 (a) and Figure 16 (b) show an animal experiment of the acoustic properties of the H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA carrier of the present invention with and without the use of a magnet result.

Fig. 17 shows the results of an animal experiment of the antitumor effect of the H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA carrier of the present invention.

Fig. 18 shows the results of thermogravimetric analysis of tumor-irradiated ultrasound in the animal experiment of the present invention.

The nineteenth chart shows the results of toxicity evaluation of the H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA carrier of the present invention.

Figure 20 shows the principle of the production of NO by the S-nitrosoglutathione (GSNO) GSNO/gold (Au)-PLGA carrier of the present invention.

The twenty-first graph shows the relationship between the GSNO concentration and the NO production in the reaction of the GSNO and the gold nanoparticles of the present invention.

The twenty-second chart shows the relationship between the concentration of the gold nanoparticles and the NO production in the reaction of the GSNO and the gold nanoparticles of the present invention.

The twenty-third graph shows the reactivity of different sizes of gold nanoparticles in the reaction of the GSNO of the present invention with the copper sulfide (Cu _2-X S) nanoparticle gold nanoparticles.

The twenty-fourth graph shows the relationship between the GSNO concentration and the NO yield in the reaction of the GSNO of the present invention with copper sulfide (Cu _2-X S) nanoparticles.

The twenty-fifth graph shows the relationship between the concentration of copper sulfide nanoparticles and the NO yield in the reaction of the GSNO and copper sulfide (Cu _2-X S) nanoparticles of the present invention.

The twenty-sixth graph shows the case of oxygen generation of the H ₂ O ₂ /Mn ₃ O ₄ -PLGA carrier of the present invention.

The details of the present invention will be apparent from the following detailed description of the preferred embodiments.

Referring to the first figure, a first embodiment of the present invention provides a use of a carrier 10 for preparing a medicament for treating a cancer, wherein the carrier 10 comprises: a hydrophilic core 101 comprising a hydrogen peroxide (H). ₂ O ₂ ) 103; and a hydrophobic outer shell 102 covering the hydrophilic core 101 and comprising a metal ion donor 104 and a polymer compound 105, wherein: the hydrogen peroxide 103 and the metal ion donor When the 104 is in contact, the hydrogen peroxide 103 generates a reactive oxygen species (ROS) 106 by generating a Fenton reaction with one of the metal ions provided by the metal ion donor 104.

The metal ion donor 104 may be a metal or metal compound nanoparticle comprising Fe ²⁺ , Cu ²⁺ , Cu ⁺ , Ce ³⁺ , Cr ²⁺ or Mo ⁵⁺ , preferably ferric oxide (Fe _{3 )} O ₄ ) nanoparticles, but are not limited thereto. The metal or metal compound nanoparticle may have a size of 1 to 30 nm, but is not limited thereto. The metal ion may be Fe ²⁺ , Cu ²⁺ , Cu ⁺ , Ce ³⁺ , Cr ²⁺ or Mo ⁵⁺ , but is not limited thereto. The polymer compound 105 may be any amphoteric polymer compound such as poly(lactic-co-glycolic acid, PLGA), but is not limited thereto. PLGA has high biocompatibility and biodegradability, and the ratio of the molecular weight of PLGA used in the present invention to lactic acid and glycolic acid is not limited by the Food and Drug Administration (FDA).

The mechanism of the Fenton reaction is as follows: (1) M ⁿ⁺ + H ₂ O ₂ → M ⁽ⁿ⁺¹⁾ + HO‧ + OH ^-

(2) M ⁽ⁿ⁺¹⁾ + H ₂ O ₂ → M ^{n +} + HOO‧ + H ⁺ The reactive oxygen species (ROS) produced by the Fenton reaction is a group of highly reactive oxygen-derived molecules, including superoxide Molecules such as anion radicals (‧O ₂ ^- ), hydroxyl radicals ( ‧ OH), singlet oxygen and hydrogen peroxide (H ₂ O ₂ ).

The treatment comprises: delivering the drug to a target site; after the drug is delivered to the target site, applying a stimulus to the target site to destroy the hydrophobic outer shell 102 of the carrier 10, wherein the stimulus is a diagnostic ultrasonic wave, a light source or a temperature; when the hydrophobic outer casing 102 is broken, the hydrogen peroxide 103 is released and brought into contact with the metal ion donor 104; and when the hydrogen peroxide 103 and the metal ion When the donor 104 is in contact, the hydrogen peroxide 103 and the metal ion provided by the metal ion donor 104 generate the Fenton reaction to form the reactive oxygen species 106.

An average intensity of the ultrasonic wave for diagnosis is 0.0001 to 10 W/cm ² , and an average frequency of the ultrasonic wave for diagnosis is 20 kHz to 100 MHz; the light source is a near-infrared light, an ultraviolet light or a visible light; and the reaction A rate of generation of the oxygen-containing species 106 is regulated by one of the intensity of the stimulus, a frequency, a time point, and a length of time.

The carrier 10 generates the reactive oxygen species to kill a cancer cell, generate oxygen as an echo source of an ultrasound image, and provide a magnetic property required for nuclear magnetic resonance imaging; and the treatment further includes: The carrier 10 is directed to the target site in a step of modifying an antibody on the surface of the carrier 10 or providing a magnetic field generating device to generate a magnetic field target. The antibody may be an antibody against a cancer cell surface antigen, and the magnetic field generating device may be a magnet, but is not limited thereto.

Please refer to the second picture. The hydrophilic core further comprises a stabilizer 107, which may be trisodium diphosphate (TSDP) or tetrasodium pyrophosphate (TSPP), but is not limited thereto. A yield of the reactive oxygen species 106 is regulated by a concentration of the hydrogen peroxide 103 and an amount of the metal ion donor 104. The surface of the carrier 10 may be modified with a positively charged molecule 108. The positively charged molecule 108 may be bovine serum albumin (BSA), but is not limited thereto. Modification of the positively charged molecule 108 prevents the carrier 10 from being engulfed by monocytes or macrophages in the blood.

Since the Fenton reaction was discovered in 1894, it has been used in the treatment of wastewater and contaminated soils and oxidized organic pollutants, as well as chemotherapy, radiotherapy and phototherapy. Although ROS plays an important role in various cell signaling pathways to regulate cell growth, overproduction of ROS can lead to oxidative damage in cell function. The role of ROS depends on its quantity. This contradiction has led to great challenges in the use of ROS stress for the development of cancer treatment. In addition, tumor cells are more vulnerable to additional ROS than normal cells. Thus, an increased amount of ROS can inhibit tumor growth. Therefore, exogenous ROS can be used to destroy cancer cells, providing a promising therapeutic option for cancer treatment. Unfortunately, the production of excess ROS is often uncontrollable.

Non-surgical treatments, including chemotherapy, radiation therapy, and phototherapy, can be used to produce ROS. Chemotherapy relies primarily on increasing endogenous ROS in cancer cells by anti-cancer drugs that produce ROS. Phototherapy is the use of photosensitizers to produce singlet oxygen. In order to achieve control of ROS, radiation therapy and phototherapy are operated by stimulating the use of electromagnetic waves through the outside world. However, the difficulty of light penetration into deep tissues is a major obstacle to phototherapy. Furthermore, in radiotherapy, radiation is used to generate free radicals on deoxyribonucleic acid (DNA), resulting in further oxidation under aerobic conditions, resulting in DNA double-strand breaks. The demand for oxygen has extremely limited the use of radiotherapy and phototherapy in hypoxic regions of solid tumors.

The carrier 10 of the present invention carries the metal ion donor 104 in the hydrophobic outer casing 102, respectively, and carries the hydrogen peroxide 103 in the hydrophilic core 101 such that the carrier 10 is destroyed resulting in contact of the hydrogen peroxide 103 with the metal ion donor 104. Naturally, the Fenton reaction is generated to generate ROS. Therefore, unlike phototherapy, photosensitizers are required to produce ROS, and it is not limited by the difficulty of penetration of deep tissue light and the lack of oxygen in the hypoxic regions of solid tumors. Moreover, the yield of the reactive oxygen species 106 is regulated by the concentration of the hydrogen peroxide 103 and the number of metal ion donors 104, and the rate of formation of the reactive oxygen species 106 is by diagnostic ultrasound. The intensity, frequency, time point and length of time of the stimulus such as light source or temperature are regulated. Solved the problem that the conventional ROS production cannot be controlled.

As mentioned earlier, ultrasonic technology has been widely used in the diagnosis of diseases. In addition to the purpose of diagnosis, high-intensity focused ultrasound (HIFU) is often used to destroy the carrier to release the drug or to ablate the malignant tumor through high temperature. Therefore, high-intensity focused ultrasound requires careful handling because it tends to cause damage to healthy tissue around the target site. Diagnostic ultrasound provides the advantage of being harmless to healthy tissue and painless to the recipient. By the present invention The carrier 10 can use imaging ultrasonic waves to simultaneously perform imaging and treatment, and avoids the danger of high-intensity focused ultrasound, which is safe, convenient, and economical to use.

Conventional methods for enhancing ultrasound images are often filled with perfluorocarbons or nitrogen in micro or nano carriers. The carrier 10 of the present invention is filled with hydrogen peroxide 103, which generates oxygen as an echo source for the ultrasound image, thereby enhancing the ultrasound image. Hydrogen peroxide 103 is cost effective, and the use of hydrogen peroxide 103 is much more economical than conventional methods.

The carrier 10 of the present invention can provide magnetic properties required for nuclear magnetic resonance imaging by having a metal ion donor 104, such as triiron tetroxide (Fe ₃ O ₄ ), and can generate a magnetic field target by providing a magnetic field generating device. The vector 10 is guided to the target site, thereby achieving the effect of the target treatment.

Referring to the third figure, a second embodiment of the present invention provides a use of a carrier 20 for preparing a medicament for treating a cardiovascular and cerebrovascular disease, wherein the carrier 20 comprises: a hydrophilic core 201 comprising an S- S-nitrosothiols (RSNO) 203; a hydrophobic outer shell 202 encapsulating the hydrophilic core 201 and comprising a catalyst 204, wherein: when the S-nitrosothiol 203 and the catalyst 204 Upon contact, a catalytic reaction is produced to form nitric oxide (NO) 206. The catalyst 204 may be a metal or metal compound nanoparticle containing Fe ²⁺ , Cu ²⁺ or Cu ⁺ , and may be, for example, a gold nanoparticle or a copper sulfide (Cu _2-X S) (0<x<1) Nai. Rice particles, but are not limited to this. The hydrophilic core 201 may further comprise a polymer compound 205, which may be a polymer compound of all amphoteric properties, such as poly(lactic-co-glycolic acid, PLGA), but not Limited to this.

The treatment comprises the steps of: delivering the drug to a target site; after the drug is delivered to the target site, applying a stimulus to the target site to destroy the carrier 20 a water-based outer casing 202, wherein the stimulus is a diagnostic ultrasonic wave, a light source or a temperature; when the hydrophobic outer casing 202 is broken, the S-nitrosothiol 203 is released and brought into contact with the catalyst 204; When the S-nitrosothiol 203 is contacted with the catalyst 204, the catalytic reaction is generated to generate the nitric oxide 206, wherein the nitric oxide 206 is used to cause at least one of vasodilation and inhibition of apoptosis, and As an echo source for an ultrasound image.

The S-nitrosothiol 203 is a S-nitrosoglutathione (GSNO), a nitrosoalbumin (AlbSNO), and an S-nitroso Valley. S-nitrosocysteine (CySNO) or a combination thereof; the catalyst 204 is a metal or a metal compound; and a yield of the nitric oxide 206 is obtained by a concentration of the S-nitrosothiol 203 The amount of the catalyst 204 is regulated.

Referring to the fourth embodiment, a third embodiment of the present invention provides a use of a carrier 30 for preparing a medicament for treating a disease, wherein the carrier 30 comprises: a hydrophilic core 301 comprising a compound 303; a hydrophobic outer shell 302 covering the hydrophilic core and comprising a metal nanoparticle 304 and an amphiphilic compound 305, wherein when the compound 303 is in contact with the metal nanoparticle 304, a chemical reaction is generated to generate A functional product 306.

The disease may be cancer or cardiovascular disease; the chemical reaction may be a Fenton reaction or a catalytic reaction, which may be a catalytic reaction for generating nitric oxide or a catalytic reaction for generating oxygen, but is not limited thereto. The compound 303 may be hydrogen peroxide or S-nitrosothiol; the metal nanoparticle 304 may be a metal containing Fe ²⁺ , Cu ²⁺ , Cu ⁺ , Ce ³⁺ , Cr ²⁺ or Mo ⁵⁺ The metal compound nanoparticle is preferably a ferroferric oxide nanoparticle, a gold nanoparticle or a copper sulfide nanoparticle, but is not limited thereto. The amphiphilic compound 305 may be a polymer compound of all amphoteric properties, such as poly(lactic-co-glycolic acid, PLGA), but is not limited thereto.

Referring to FIG. 5, a fourth embodiment of the present invention provides a carrier 40 comprising: a hydrophilic core 401 comprising a substance 403; and a hydrophobic outer shell 402 covering the hydrophilic core 401 and including a Rice particles 404 and an amphiphilic compound 405, wherein a functional product 406 is formed when the material is contacted with the nanoparticle to produce a chemical reaction.

The substance 403 may be a compound which may be hydrogen peroxide or S-nitrosothiol, but is not limited thereto. The nanoparticle 404 can be a metal or metal compound nanoparticle, and the metal or metal compound nanoparticle can be composed of Fe ²⁺ , Cu ²⁺ , Cu ⁺ , Ce ³⁺ , Cr ²⁺ or Mo ⁵⁺ . The metal or metal compound nanoparticle is preferably a ferroferric oxide nanoparticle, a gold nanoparticle or a copper sulfide nanoparticle, but is not limited thereto. The amphiphilic compound 405 may be any amphoteric polymer compound such as poly(lactic-co-glycolic acid, PLGA), but is not limited thereto. The chemical reaction may be a Fenton reaction or a catalytic reaction, which may be a catalytic reaction for generating nitric oxide or a catalytic reaction for generating oxygen, but is not limited thereto.

Experimental example

1. Preparation of Fe ₃ O ₄ -PLGA carrier and H ₂ O ₂ /Fe ₃ O ₄ -PLGA carrier:

Please refer to the sixth figure (a) to the sixth figure (f). In the first emulsification process (water/oil, w/o), hydrogen peroxide (H ₂ O ₂ ) and trisodium diphosphate (TSDP) or tetrasodium pyrophosphate (TSPP) (stabilized) The agent is loaded into a hydrophilic core of a poly(lactic-co-glycolic acid, PLGA) carrier. The method is to first prepare a 4 mL dichloromethane oil phase solution containing 10 mg/mL poly(lactic-co-glycolic acid, PLGA), and an aqueous phase solution containing 8 mg of polyvinyl alcohol (PVA). Dissolved in x mL deionized with y μL 30% H ₂ O ₂ (y=0, 200, 400 and 600) and 10 μL 0.1M TSDP or TSPP (x=0.6 at 200μL, x=0.4 and 600μL at 400μL) When x = 0.2). During the first emulsification, the oil phase solution was slowly added to the PVA solution under ultrasonic treatment, followed by an ice water bath for 2 hours. Next, in the second emulsification process (water/oil/water, w/o/w), ferroferric oxide (Fe ₃ O ₄ ) nanoparticles (10.6 ± 0.8 nm) are embedded in the hydrophobic shell of the PLGA carrier. in. The method of triiron tetroxide 1400ppm Fe ₃ O ₄ nanoparticles dispersed in 0.5mL of dichloromethane, and then added to the first solution emulsified. In order to embed Fe ₃ O ₄ nanoparticles into the PLGA shell, the emulsified solution containing Fe ₃ O ₄ nanoparticles was first added dropwise to 12 ml (10 mg/mL) of PVA solution, and homogenized using an ice bath for 20 minutes. . Figure 6 (a) and Figure 6 (b) are transmission electron microscope (TEM) images of hydrogen peroxide-free Fe ₃ O ₄ -PLGA carrier, respectively, showing synthetic Fe ₃ O ₄ The -PLGA carrier (412 ± 86 nm) was spherical in shape, and 10-nm Fe ₃ O ₄ nanoparticles were successfully embedded therein. Figure 6 (c) and Figure 6 (d) are respectively Fe ₃ O ₄ -PLGA carriers containing hydrogen peroxide (H ₂ O ₂ /Fe ₃ O ₄ -PLGA(H ₂ O ₂ /Fe ₃ O ₄ - Transmissive electron microscope image of PLGA)). During the first emulsification, the concentration of hydrogen peroxide (H ₂ O ₂ ) can be adjusted to determine the amount of carrier injected. Three different concentrations of hydrogen peroxide (200, 400 and 600 μl) were injected into the H ₂ O ₂ /Fe ₃ O ₄ -PLGA carrier, respectively. It can be seen from the sixth graph (e) and the sixth graph (f) that the different concentrations of hydrogen peroxide do not cause significant changes in the morphology and size of the support structure. The PLGA concentration during the preparation may be 0.01-1000 mg/mL; the PVA concentration may be 0.01-100 mg/mL; the Fe ₃ O ₄ nanoparticle concentration may be 0-10000 ppm; the stabilizer concentration may be 0.001 M-10 M; and H ₂ O ₂ can be 0-600 μL.

2. Colorimetric test of H ₂ O ₂ /Fe ₃ O ₄ -PLGA carrier and H ₂ O ₂ /PLGA carrier:

Please refer to Figure 7 (a) and Figure 7 (b). The principle of this test is that the reaction of potassium iodide and hydrogen peroxide produces yellow color, and the yellow color is derived from the reaction product I ₃ ^- of potassium iodide (KI) and hydrogen peroxide. The color of the 0.1 M potassium iodide solution added to the Fe ₃ O ₄ -PLGA carrier did not change; a 0.1 M potassium iodide solution added with H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA carrier was heated to 45 ° C to produce a yellow color. The concentration of hydrogen peroxide in the carrier is then quantified by the absorption value of I ₃ ^- , which is obtained from a fixed concentration of potassium iodide and different concentrations of hydrogen peroxide. The carrier injecting 200, 400 and 600 μl of hydrogen peroxide was heated in an excess of 0.1 M potassium iodide solution at 50 ° C for 15 minutes, followed by centrifugation to obtain a yellow supernatant for UV/visible measurement, and the result was 200, 400 and 600 μl peroxidation. The hydrogen peroxide carrier had a hydrogen peroxide concentration of 3.5, 8.6, and 14.3 mM, respectively.

3. Modification of bovine serum albumin (BSA) on H ₂ O ₂ /Fe ₃ O ₄ -PLGA carrier:

In order to prevent the vector from being phagocytosed by monocytes or macrophages in the blood, the surface of the positively charged BSA modified H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA carrier was added to electrostatically interact with the negatively charged PLGA. effect. BSA was attached to the surface of H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA carrier, and then centrifuged to collect the supernatant for UV/visible measurement, and the result was adsorbed to H ₂ O ₂ /Fe ₃ O ₄ -PLGA. The BSA concentration of the carrier was 1.63 μg BSA in a 100 ppm H ₂ O ₂ /Fe ₃ O ₄ -PLGA carrier.

4. Safety evaluation of H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA and Fe ₃ O ₄ -PLGA carriers:

Please refer to the eighth picture. To assess the safety of the vector, different concentrations of H ₂ O ₂ (600 μL)/Fe ₃ O ₄ -PLGA and Fe ₃ O ₄ -PLGA carriers were added to HeLa cells. Cell viability was measured after one day of culture, and the results showed that H ₂ O ₂ (600 μL)/Fe ₃ O ₄ -PLGA and Fe ₃ O ₄ -PLGA carriers were not toxic to HeLa cells.

5. Stability evaluation of H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA carrier:

Stability evaluation showed that H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA carrier can be dispersed in phosphate buffered saline (PBS) (pH 7), PBS (pH 5), cell culture medium at 37 °C. (Dulbecco's modified Eagle medium, DMEM) and 10% fetal bovine serum did not form a precipitate for seven days. However, it can be seen from the ninth figure that the H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLG carrier in PBS (pH 5) produces pores, indicating that the acidic environment promotes decomposition of the carrier. H ₂ O ₂ /Fe ₃ O ₄ -PLGA can therefore be used as a pH-sensitive drug delivery vehicle to gradually release therapeutic substances in an acidic environment.

6. Micro-ultrasonic-triggered H ₂ O ₂ /Fe ₃ O ₄ -PLGA carrier disintegration:

Under the illumination of the micro-ultrasonic diagnostic probe (VisualSonics, 40MHz), the carrier exhibits a supersonic-triggered disintegration, presumably from the cavitation effect. Please refer to the tenth figure. When the exposure time is prolonged, the ultrasonic treatment process promotes the gradual destruction of the carrier, and the structure of the carrier is completely destroyed after the ultrasonic irradiation for 30 minutes. In addition, damage of the carrier (Delta Ultrasonic Cleaner D200H) was also observed at 37 ° C, 43 KHz ultrasonic.

7. The carrier will produce O ₂ under ultrasonic illumination:

Please refer to Figure 11. In order to present a carrier ₂ on O, O ₂ sensitive to the use of the indicator Ru (dpp) proved ₃ Cl _2, O ₂ in the presence of which causes a reduction of the fluorescence intensity. Preparation of a packed H ₂ O ₂ -free PLGA (H ₂ O ₂ -PLGA) carrier containing no Fe ₃ O ₄ to react with Ru(dpp) ₃ Cl ₂ , when H ₂ O ₂ (600 μL)-PLGA was irradiated with ultrasonic wave 30 When the carrier was destroyed in minutes, the fluorescence of Ru(dpp) ₃ Cl ₂ was markedly lowered, indicating that O ₂ was released. In the absence of ultrasonic triggering, the fluorescence of Ru(dpp) ₃ Cl ₂ did not decrease because no O ₂ was released.

8. The carrier produces acoustic properties in vitro outside the agar gel model:

Please refer to Figure 12. Next, H ₂ O ₂ (600 μL)/Fe ₃ O ₄ -PLGA polymer vesicles were tested for in vitro echogenic performance in vitro on an agar gel model. Fe ₃ O ₄ -PLGA without H ₂ O ₂ did not produce an echo signal under ultrasonic exposure. Conversely, an appreciable echo signal was captured in the conventional B mode and was observed immediately after H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA injection into the gel, indicating that the O ₂ generation is ultrasonic resonance. the reason. Contrast strengthens for at least 30 minutes.

8. Confirm that Fe ₃ O ₄ nanoparticles can react with H ₂ O ₂ to produce reactive oxygen species:

Please refer to the thirteenth map. Due to the deformation of the ultrasonic trigger carrier, the encapsulated H ₂ O ₂ can penetrate and react with the degraded PLGA and Fe ₃ O ₄ encapsulated in the carrier film to generate hydroxyl radicals (‧OH, one of the reactive oxygen species) . To confirm the Fe ₃ O ₄ nanoparticles and H ₂ O ₂ can react and produce ‧OH, the use of Fe ₃ O ₄ @PLGA experiment, Fe ₃ O ₄ @PLGA preparation method is Fe ₃ O ₄ nanoparticles coated Transfer to the aqueous phase solution after the upper PLGA. 3'-(p-aminophenyl)fluorescein (APF) was used as a reagent for the efficient detection of ‧ OH, which reacts with ‧ OH to emit intense fluorescence at 520 nm, which can be measured to determine the formation of ‧ OH The result contained a solution of Fe ₃ O ₄ @PLGA nanoparticles and H ₂ O ₂ to rapidly produce ‧ OH. And after a reaction time of 15 minutes, the fluorescence of the solution was increased by 2.5 times, and it was confirmed that a mixture of Fe ₃ O ₄ @PLGA nanoparticles and H ₂ O ₂ can carry out a Fenton reaction. The fluorescence of the solution in which TSPP was added to a solution containing Fe ₃ O ₄ @PLGA nanoparticles and H ₂ O ₂ was increased by a factor of 1.8, indicating that TSPP provided a certain degree of H ₂ O ₂ stabilization.

9. Relationship between ultrasonic irradiation time and the yield of reactive oxygen species:

Please refer to Figure 14. To further understand how the H ₂ O ₂ /Fe ₃ O ₄ -PLGA carrier generates hydroxyl radicals (‧OH) under the influence of ultrasonic fields, the H ₂ O ₂ /Fe ₃ O ₄ -PLGA carriers are carried out at different times. Ultrasonic irradiation was used to observe the formation of ‧ OH. The H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA carrier, which received longer-time ultrasonic illumination, resulted in more ‧ OH production because the structurally increased damage resulted in a stronger Fenton reaction.

10. Animal experiments with acoustic properties of H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA carrier:

Please refer to the fifteenth figure. In nude mice were injected intratumorally to demonstrate the potential of H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA vectors for tumor ultrasound imaging. Nude mice bearing HeLa cell carcinoma tumors received a dose of 5 mg [Fe]/kg. The contrast according to the B mode (VisualSonics, 40MHz) is recorded at different time intervals (5, 15 and 30 minutes), which shows a significant contrast enhancement and the quantitative increase of the gray scale to the maximum intensity within 5 minutes of the ultrasonic field . Although the echo signal shows a decreasing trend with prolonged exposure time, continuous imaging can be as long as 30 minutes, which is consistent with the results of the in vitro agar gel model.

11. Animal experiments for the acoustic properties of H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA carriers with and without magnets:

Please refer to Figure 16 (a). Intravenous administration via tail vein injection for further evaluation of the acoustic properties of the ultrasonic generation of the H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA carrier. Since the H ₂ O ₂ (600 μL)/Fe ₃ O ₄ -PLGA support has favorable magnetic properties, the attractiveness of using and not using magnets is separately performed to compare the contrast enhancement. Tumor-bearing mice received an intravenous injection of 5 mg [Fe]/kg twice. In the case of the attraction of the magnet, after each injection, the magnet was placed on the tip of the tumor for 20 minutes. After the second injection of the vector, the ultrasound contrast of the tumor tissue (size: 405 mm ³ ) immediately became bright and the intensity of the gray scale increased. The enhancement gradually peaked in 15 minutes and then decreased slightly after 30 minutes of exposure. On the contrary, it was not observed that the group without the magnet had any contrast enhancement during the ultrasonic irradiation for 30 minutes.

See Figure 16 (b), which shows the MR imaging visibility to monitor the accumulation of carriers after the same intravenous procedure. Tumor (405mm ³ ) using 9.4 Animal micro nuclear magnetic resonance imaging system (micro MRI system). After the second injection, the contrast of the tumor darkened and the signal continued to drop to 77% after 30 minutes of exposure to ultrasound. Although the carrier was destroyed after exposure to ultrasound for 30 minutes based on the tenth image, the released Fe ₃ O ₄ nanoparticles remaining in the tumor continued to contribute to magnetic resonance imaging. The contrast change of the smaller tumor group was similar.

12. Animal experiment of anti-tumor effect of H ₂ O ₂ (600 μL)/Fe ₃ O ₄ -PLGA carrier:

Please refer to Figure 17. Excessive production of reactive oxygen species can lead to oxidative damage to cellular function. In addition, cancer cells are more vulnerable to damage caused by extra reactive oxygen species than normal cells. Thus, the generation of ‧ OH after ultrasound triggering provides a cancer therapy that inhibits tumor growth. HeLa cells were subcutaneously transplanted into the thighs of nude mice, and fifteen nude mice with HeLa tumors were divided into five groups. For PBS, PBS plus ultrasonic, carrier plus ultrasonic, carrier plus magnet and carrier plus ultrasonic / magnet. Mice received two consecutive injections of 5 mg [Fe]/kg via the tail vein in accordance with the same dosing procedure as ultrasound and MRI. Considering the information obtained from TEM, ultrasound and MRI, the group of mice treated with PBS plus ultrasound, carrier plus ultrasound and carrier plus ultrasound/magnetism experienced 30 minutes of ultrasound after each intravenous injection. Irradiation. The degenerative efficacy of tumor growth is monitored as changes in tumor volume. Magnetic resonance imaging of the tumor tissue after 24 hours revealed that the contrast continued to improve the negative contrast effect, which may suggest that the vector continues to accumulate in the tumor.

Ultrasound-treated mice received 1 hour of additional ultrasound exposure on day 2. The group using magnet attraction is statistically significant in antitumor effect, indicating that the amount of the vector located in the tumor is an important therapeutic factor. When the attraction of the magnet is provided without ultrasound, tumor growth is inhibited in the first 8 days, but slowly relapses as the number of days increases. The initial inhibition may be caused by carrier degradation and release of ‧ OH in the acidic environment of the tumor. Conversely, focusing the magnetic target carrier on the tumor plus ultrasound illumination results in complete tumor growth inhibition. Ultrasonic triggering and degradation of the carrier under acidic conditions contribute to this effective anti-tumor effect.

13. Thermogravimetric analysis of tumor-irradiated ultrasound:

Please refer to Figure 18. Thermogravimetric analysis of tumor temperature was performed using a Thermo Tracer H2640 (NEC, Japan) camera to monitor the course of the tumor during ultrasound exposure (30 minutes), with the tumor location indicated as P1. As a result, the temperature was continuously maintained at about 22 ° C with no sign of increase, indicating a non-thermal process under the ultrasonic field.

14. Toxicity assessment of H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA carrier:

Please refer to the nineteenth figure. For toxicity assessment of the vehicle, 5 mg [Fe]/kg of H ₂ O ₂ (600 μL) / Fe ₃ O ₄ -PLGA vector was injected via the tail vein in healthy mice without tumor. All mice survived during the 30-day experiment. The biological distribution indicates that the vector is gradually eliminated within one month. In addition, histology and blood biochemical analysis showed no acute toxicity as a cancer drug.

15. The method of the present invention uses gold nanoparticles and S-nitrosoglutathione (GSNO) for cardiovascular diseases:

Please refer to the twentieth map. GSNO was loaded into the hydrophilic core of the PLGA carrier, and 4 nm of oil phase gold nanoparticles were embedded in a hydrophobic shell to form a GSNO/Au-PLGA vector. After the GSNO/Au-PLGA vector was injected into the organism, Applying a 600 nm near-infrared laser or ultrasonic wave to the affected part, the gold nanoparticles can absorb the near-infrared light in the band to generate heat, and the high temperature or ultrasonic wave can generate the PLGA shell of the GSNO/Au-PLGA carrier. The hole is broken, and then the GSNO is released. When GSNO flows through the surface of the gold nanoparticles, the sulfur on the GSNO is bonded to the surface of the gold nanoparticles, and then nitric oxide (NO) gas is released to carry out the heart. Treatment of vascular disease.

16. Relationship between GSNO concentration and NO production:

Please refer to the twenty-first figure. Producing NO at a fixed concentration (100 ppm) of 13 nm gold nanoparticles and GSNO at different concentrations (10 ^-7 , 10 ^-6 , 10 ^-5 , 10 ^-4 , 10 ^{-3 ,} and 5 × 10 ^-3 M ), The content of NO was measured by a Nitric Oxide Colorimetric Assay Kit (BioVision K262-200). As a result, it was found that as the concentration of GSNO increases, the amount of NO produced also increases.

17. Relationship between the concentration of gold nanoparticles and the yield of NO:

Please refer to the twenty-second figure. The GSNO at a fixed concentration (5×10 ^-3 M) is reacted with 13 nm gold nanoparticles of different concentrations (0 ppm, 10 ppm, 20 ppm, 30 ppm, 50 ppm, 100 ppm, 200 ppm, 300 ppm, and 400 ppm) to produce NO. The result can be found in gold. When the concentration of the nanoparticle reaches 100 ppm or more, the upper limit of NO production can be obtained.

18. Reactivity of different sizes of gold nanoparticles:

Please refer to the twenty-third figure. Using a fixed concentration (100 ppm) of 4 nm gold nanoparticles to react with different concentrations (10 ^-7 , 10 ^-6 , 10 ^-5 , 10 ^-4 , 10 ^{-3 ,} and 10 ^-2 M ) of GSNO to produce NO, the lowest The concentration of GSNO producing NO is 10 ^-4 M, that is, the 4 nm gold nanoparticle has higher reactivity than the 13 nm gold nanoparticle.

19. Carrier of copper sulfide (Cu _2-X S) nanoparticles and GSNO:

4nm oil phase copper sulfide (Cu _2-X S) nanoparticles are embedded in the PLGA hydrophobic shell, and GSNO is loaded in the hydrophilic core to form GSNO/Cu _2-X S-PLGA carrier when irradiated with 633 nm laser. After the carrier, Cu _2-X S absorbs energy and generates high temperature, which destroys the PLGA spherical shell and releases GSNO, which flows through the surface of copper sulfide to react with Cu ⁺ to form NO. Therefore, it can be applied to cardiovascular diseases. Its reaction formula is as follows:

20. Relationship between GSNO concentration and NO production:

Please refer to the twenty-fourth figure. The yield of NO was measured using a Nitric Oxide Colorimetric Assay Kit (BioVision K262-200). A fixed concentration (100ppm) of 4nm Cu _2-X S nanoparticles can react with GSNO at different concentrations (10 ^-7 , 10 ^-6 , 10 ^-5 , 10 ^-4 , 10 ^-3 and 10 ^-2 M ) to produce NO The lowest GSNO concentration of NO is 10 ^-3 M.

21. Relationship between copper sulfide nanoparticle concentration and NO production:

Please refer to the twenty-fifth map. A fixed concentration (10 ^-3 M) of GSNO reacted with different concentrations (0 ppm, 10 ppm, 20 ppm, 30 ppm, 50 ppm, 100 ppm, 200 ppm, 300 ppm, and 400 ppm) of Cu _2-X S nanoparticles to produce NO, which was found to be Cu _{2 When the} concentration of the _-X S nanoparticle reaches 100 ppm or more, the upper limit of NO production can be obtained.

22. Use manganese oxide and hydrogen peroxide to produce oxygen:

The oil phase 10 nm trimanganese tetraoxide (Mn ₃ O ₄ ) nanoparticle is embedded in the hydrophobic outer shell of the PLGA carrier, and the hydrophilic core is loaded with H ₂ O ₂ aqueous solution to form H ₂ O ₂ /Mn ₃ O. _4- PLGA carrier, which can be applied to the biomedical field as a developer of magnetic resonance imaging and ultrasonic waves, and injects H ₂ O ₂ /Mn ₃ O ₄ -PLGA carrier into living organisms, when H ₂ O ₂ /Mn _{When the 3} O ₄ -PLGA carrier accumulates at the tumor site, it is in an acidic environment, when a large amount of hydrogen protons flow into the H ₂ O ₂ /Mn ₃ O ₄ -PLGA carrier, and when flowing through the surface of Mn ₃ O ₄ , Dissolving Mn ²⁺ ions and diffusing away from the carrier will also flow into the core of the carrier. A large amount of Mn ²⁺ ions can provide the development effect of magnetic resonance imaging T1 (image becomes bright), while Mn ²⁺ flowing into the nucleus will The H ₂ O ₂ reaction produces a large amount of oxygen, which can provide significant ultrasonic development capabilities. Compared with a carrier containing only hydrogen peroxide, although it also has ultrasonic development ability, it cannot enhance the developing ability in an acidic environment, and the H ₂ O ₂ /Mn ₃ O ₄ -PLGA carrier is in an acidic environment (tumor). Under the magnetic resonance imaging development ability, on the other hand, there is a more significant ultrasonic development effect.

23. H ₂ O ₂ /Mn ₃ O ₄ -PLGA carrier oxygen generation:

Please refer to the twenty-sixth figure. Figure 26 shows the oxygen generation of the H ₂ O ₂ /Mn ₃ O ₄ -PLGA carrier. The measurement of oxygen is based on Ru(dpp) ₃ Cl ₂ as the detection reagent (the lower the percentage of fluorescence, the more oxygen is produced. As a result, it was found that the H ₂ O ₂ /Mn ₃ O ₄ -PLGA carrier produced a larger amount of oxygen under acidic conditions.

Example

A use of a carrier for the preparation of a medicament for treating a cancer, wherein the carrier comprises: a hydrophilic core comprising a hydrogen peroxide (H ₂ O ₂ ); and a hydrophobic outer shell encapsulating the hydrophilic a core comprising a metal ion donor and a polymer compound, wherein: when the hydrogen peroxide is contacted with the metal ion donor, the hydrogen peroxide is generated from a metal ion provided by the metal ion donor A reactive Fenton reaction produces a reactive oxygen species (ROS).

2. The use of embodiment 1, wherein the treating comprises: delivering the drug to a target site; after the drug is delivered to the target site, applying a stimulus to the target site to destroy the carrier The hydrophobic outer casing, wherein the stimulus is a diagnostic ultrasonic wave, a light source or a temperature; when the hydrophobic outer casing is broken, the hydrogen peroxide is released and contacts the metal ion donor; and when When hydrogen peroxide is in contact with the metal ion donor, the hydrogen peroxide and the metal The metal ion provided by the ion donor generates the Fenton reaction to form the reactive oxygen species.

3. The use of embodiment 1-2, wherein: an average intensity of the diagnostic ultrasonic wave is 0.0001 - 10 W/cm ² , and an average frequency of the diagnostic ultrasonic wave is 20 kHz - 100 MHz; A near-infrared light, an ultraviolet light, or a visible light; and a rate of generation of the reactive oxygen-containing species is regulated by one of the intensity, a frequency, a time point, and a length of time of the stimulus.

4. The use of embodiment 1-3, wherein: the vector generates the reactive oxygen species to kill a cancer cell, generate oxygen as an echo source of an ultrasound image, and provide nuclear magnetic resonance imaging a desired magnetic property; and the treatment further comprises: directing the carrier to the target site by a step of modifying an antibody on the surface of the carrier or providing a magnetic field generating device to generate a magnetic field target .

5. The use of any of embodiments 1-4, wherein: the hydrophilic core further comprises a stabilizer; the metal ion provided by the metal ion donor is Fe ²⁺ , Cu ²⁺ , Cu ⁺ , Ce ³⁺ , Cr ²⁺ , Mo ⁵⁺ or a combination thereof; and a yield of the reactive oxygen species is regulated by a concentration of the hydrogen peroxide and an amount of the metal ion donor.

6. Use of a carrier for the preparation of a medicament for the treatment of a cardiovascular disease, wherein the carrier comprises: a hydrophilic core comprising an S-nitrosothiols (RSNO); a hydrophobic outer shell encapsulating the hydrophilic core and comprising a catalyst, wherein: when the S-nitrosothiol Upon contact with the catalyst, a catalytic reaction is produced to form nitric oxide (NO).

7. The use of embodiment 6, wherein the treatment comprises the steps of: delivering the drug to a target site; after the drug is delivered to the target site, applying a stimulus to the target site to destroy a hydrophobic outer shell of the carrier, wherein the stimulus is a diagnostic ultrasonic wave, a light source or a temperature; when the hydrophobic outer shell is destroyed, the S-nitrosothiol is released and contacted with the catalyst; When the S-nitrosothiol is contacted with the catalyst, the catalytic reaction is generated to generate the nitric oxide, wherein the nitric oxide is used to cause at least one of vasodilation and inhibition of apoptosis, and as one An echo source for ultrasound images.

8. The use according to any of embodiments 6-7, wherein the S-nitrosothiol is a S-nitrosoglutathione (GSNO), an S-nitroso white Protein (S-nitrosoalbumin, AlbSNO), S-nitrosocysteine (CySNO) or a combination thereof; the catalyst is a metal or a metal compound; and a yield of the nitric oxide is borrowed A concentration of the S-nitrosothiol is regulated by a quantity of the catalyst.

9. A use of a carrier for the preparation of a medicament for treating a disease, wherein the carrier comprises: a hydrophilic core comprising a compound; A hydrophobic outer shell encasing the hydrophilic core and comprising a metal nanoparticle and an amphoteric compound, wherein when the compound is in contact with the metal nanoparticle, a chemical reaction is generated to form a functional product.

10. A carrier comprising: a hydrophilic core comprising a substance; a hydrophobic outer shell encasing the hydrophilic core and comprising a nanoparticle and an amphiphilic compound, wherein: the substance and the nanoparticle When a chemical reaction occurs upon contact, a functional product is formed.

40‧‧‧ Carrier

401‧‧‧Hydrophilic core

402‧‧‧hydrophobic shell

403‧‧‧ substances

404‧‧‧Nano particles

405‧‧‧Amphiphilic compounds

406‧‧‧ functional product

Claims (10)

A use of a carrier for the preparation of a medicament for treating a cancer, wherein the carrier comprises: a hydrophilic core comprising a hydrogen peroxide (H ₂ O ₂ ); and a hydrophobic outer shell encapsulating the hydrophilic core And comprising a metal ion donor and a polymer compound, wherein: when the hydrogen peroxide is in contact with the metal ion donor, the hydrogen peroxide and the metal ion provided by the metal ion donor generate a fen A reactive reaction (Fenton reaction) produces a reactive oxygen species (ROS). The use of claim 1, wherein the treatment comprises: delivering the drug to a target site; after the drug is delivered to the target site, applying a stimulus to the target site to destroy the target a hydrophobic outer shell of the carrier, wherein the stimulus is a diagnostic ultrasonic wave, a light source or a temperature; when the hydrophobic outer shell is broken, the hydrogen peroxide is released and contacts the metal ion donor; and when When hydrogen peroxide is contacted with the metal ion donor, the hydrogen peroxide and the metal ion provided by the metal ion donor generate the Fenton reaction to form the reactive oxygen species. The application of claim 2, wherein: an average intensity of the diagnostic ultrasonic wave is 0.0001 - 10 W/cm ² , and an average frequency of the diagnostic ultrasonic wave is 20 kHz - 100 MHz; Near-infrared light, ultraviolet light or a visible light; and a rate of generation of the reactive oxygen species is regulated by one of the intensity, a frequency, a time point, and a length of time of the stimulus. The use of claim 1, wherein the carrier generates the reactive oxygen species to kill a cancer cell, generate oxygen as an echo source of an ultrasound image, and provide a nuclear magnetic resonance imaging A magnetic property is required; and the treatment further comprises: directing the carrier to the target site by a step of modifying an antibody on the surface of the carrier or providing a magnetic field generating device to generate a magnetic field target. The use according to claim 1, wherein the hydrophilic core further comprises a stabilizer; the metal ion provided by the metal ion donor is Fe ²⁺ , Cu ²⁺ , Cu ⁺ , Ce ^{3 +} , Cr ²⁺ , Mo ⁵⁺ or a combination thereof; and a yield of the reactive oxygen species is regulated by a concentration of the hydrogen peroxide and an amount of the metal ion donor. A use of a carrier for the preparation of a medicament for treating a cardiovascular disease, wherein the carrier comprises: a hydrophilic core comprising a S-nitrosothiols (RSNO); a hydrophobic shell, comprising The hydrophilic core is coated and comprises a catalyst, wherein: when the S-nitrosothiol is contacted with the catalyst, a catalytic reaction is generated to generate nitric oxide (NO). The use of claim 6, wherein the treatment comprises the step of delivering the drug to a target site; After the drug is delivered to the target site, the target site is stimulated to destroy the hydrophobic outer shell of the carrier, wherein the stimulus is a diagnostic ultrasound, a light source or a temperature; when the hydrophobicity When the outer shell is destroyed, the S-nitrosothiol is released and contacted with the catalyst; and when the S-nitrosothiol is contacted with the catalyst, the catalytic reaction is generated to form the nitric oxide, wherein Nitric oxide is used to cause at least one of vasodilation and inhibition of apoptosis, and as an echo source of an ultrasound image. The use according to claim 6, wherein the S-nitrosothiol is an S-nitrosoglutathione (GSNO), an S-nitroso albumin. (S-nitrosoalbumin, AlbSNO), an S-nitrosocysteine (CySNO) or a combination thereof; the catalyst is a metal or a metal compound; and a yield of the nitric oxide is obtained by A concentration of the S-nitrosothiol is adjusted with a quantity of the catalyst. A use of a carrier for the preparation of a medicament for treating a disease, wherein the carrier comprises: a hydrophilic core comprising a compound; and a hydrophobic outer shell encapsulating the hydrophilic core and comprising a metal nanoparticle And an amphoteric compound, wherein: when the compound is contacted with the metal nanoparticle, a chemical reaction is generated to form a functional product. A carrier comprising: a hydrophilic core comprising a substance; A hydrophobic outer shell encasing the hydrophilic core and comprising a nanoparticle and an amphoteric compound, wherein: when the material contacts the nanoparticle to generate a chemical reaction, a functional product is formed.