JP2010242059A - Fluorescent particle and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for producing fluorescent particles. <P>SOLUTION: The method for producing fluorescent particle is a process of irradiating a target 7 in a solvent 5 with a laser beam 2. Therein, the target is preferably made of Sr<SB>2</SB>MgSi<SB>2</SB>O<SB>7</SB>:Er, Dy, SrAl<SB>2</SB>O<SB>4</SB>:Eu, Dy, SrAl<SB>2</SB>O<SB>4</SB>:Eu, Sr<SB>4</SB>Al<SB>14</SB>O<SB>25</SB>:Eu, Dy, Ca<SB>2</SB>Al<SB>2</SB>SiO<SB>7</SB>:Ce, CaAl<SB>2</SB>O<SB>4</SB>:Eu, Nd, Lu<SB>2</SB>SiO<SB>5</SB>:Ce, ZnS:Cu, CaSrS:Bi, CaS:Eu, Tm. Further, the liquid is preferably a polar solvent such as pure water, methanol, ethanol and propanol and a nonpolar solvent such as hexane and benzene. Furthermore, a substance to be added to the liquid is preferably an anionic surfactant such as sodium dodecyl sulfate, a cationic surfactant such as cetyltrimethylammonium bromide, an ampholytic surfactant such as alkylcarboxybetaine and a nonionic surfactant such as polyethylene glycol and polyvinylpyrrolidone. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

The present invention relates to a novel fluorescent particle.
The present invention also relates to a novel method for producing fluorescent particles.

  Conventionally, nanoparticles having a particle size of nanometer size are called colloids and have been studied for a long time, but in recent years, they have attracted attention because of their optical specificity. Production methods can be broadly classified into gas phase methods and liquid phase methods, but in biomedical applications and the like, nanoparticles in a liquid are often used, and the liquid phase method is considered suitable.

  Conventional liquid phase methods include precipitation methods, sol-gel methods, solvothermal methods, hot soap methods, and the like. As a result, many quantum dots and doped phosphors have been produced and their application has been studied. However, there have been no examples of nanoparticles having afterglow characteristics dispersed in a solution. Afterglow characteristics indicate a phenomenon in which fluorescence is emitted for a long time after the excitation light is cut off, and there have been many reports (for example, see Non-Patent Documents 1 and 2). An agglomerated solid.

  Bioimaging, on the other hand, stains a specific site or cell in a living body with a marker, accelerates research and development in the biomedical field, and is useful for early diagnosis. This utilizes the phenomenon of emitting visible light fluorescence when the marker is irradiated with excitation light such as ultraviolet light.

  As the marker, organic fluorescent dyes such as cyanine dyes, fluorescein dyes, rhodamine dyes and the like are used (for example, see Non-Patent Document 3). In recent years, nanoparticles such as quantum dots have been studied for bioimaging.

  On the other hand, there is photodynamic therapy (PDT: Photo-Dynamic Therapy) as one of the cancer treatment methods (for example, see Non-Patent Documents 4 to 6). In this method, a photosensitizing substance such as porphyrin is accumulated in cancer cells and irradiated with light through an optical fiber to generate active oxygen and kill the cancer cells.

  This is a problem that occurs after the administration of an anticancer drug, causing side effects on various normal cells in the body. Is a revolutionary way of killing.

Murayama Yoshio, Nikkei Science, May 1, 22-29 (1996). T. Matsuzawa, et al. J. Electrochem. Soc. 143 (1996) 2670. The Handbook-A Guide to Fluorescent Probes and Labeling Technologies, Tenth Edition: Molecular Probes Invitrogen detection technologies T. J. Dougherty, et al: J. Natl. Cancer Inst. 90 (1998) 889. W. M. Sharman, et al: J. E. Drug Discovery Today 4 (1999) 507. (S. B. Brown: Lancet Oncol, 5 (2004) 497.)

  However, as described above, many quantum dots and doped phosphors have been produced and their application has been studied. However, there have been no examples of nanoparticles having afterglow properties dispersed in a solution. . There have been many reports so far, but all are solids which are crystals or polycrystal aggregates.

  In addition, since the organic dyes and quantum dots described above do not have afterglow characteristics, it is necessary to continuously irradiate excitation light such as high-intensity ultraviolet light when used as a marker. At this time, when the marker is irradiated with ultraviolet light, the living body is also irradiated with ultraviolet light. High-intensity ultraviolet light has cytotoxicity, causes many changes in the living body, and has a problem that it may not be possible to image the original state of the living body.

  In addition, since the organic dyes and quantum dots described above do not have afterglow characteristics, it is necessary to continue irradiation with excitation light when used as a marker. At this time, when the marker is irradiated with excitation light, the living body is also irradiated with excitation light. There are substances that exhibit fluorescence, such as chlorophyll and flavin, in the living body, and when these fluorescent substances are used as markers, autofluorescence that also emits these substances together is generated, and clear imaging is possible. There is a problem that cannot be done.

In addition, the photodynamic therapy (PDT) described above has a problem that only the cancer cells that can reach the optical fiber can be treated, and the applicable range is narrow.
Therefore, development of a novel fluorescent particle and a manufacturing method thereof that solve such a problem is desired.

This invention is made | formed in view of such a subject, and it aims at providing a novel fluorescent particle.
Another object of the present invention is to provide a novel method for producing fluorescent particles.

  In order to solve the above-mentioned problems and achieve the object of the present invention, the fluorescent particle manufacturing method of the present invention is a fluorescent particle manufacturing method in which a target in liquid is irradiated with laser light, wherein the target has afterglow characteristics. A method comprising a fluorescent material.

Here, although not limited, the target material is Sr ₂ MgSi ₂ O ₇ : Er, Dy, SrAl ₂ O ₄ : Eu, Dy, SrAl ₂ O ₄ : Eu, Sr ₄ Al ₁₄ O ₂₅ : Eu, Dy, Ca ₂ Al ₂ SiO ₇ : Ce, CaAl ₂ O ₄ : Eu, Nd, Lu ₂ SiO ₅ : Ce, ZnS: Cu, CaSrS: Bi, CaS: Eu, Tm Any two or more combinations are preferable. In addition, although not limited, the liquid may be any one of a polar solvent such as pure water, methanol, ethanol, and propanol, and a nonpolar solvent such as hexane and benzene, or a combination of any two or more thereof. Preferably there is. Further, although not limited, what is added to the liquid is an anionic surfactant such as sodium dodecyl sulfate (SDS), a cationic surfactant such as cetyltrimethylammonium bromide (CTAB), an alkyl carboxy betaine, etc. These are amphoteric surfactants, and nonionic surfactants such as polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP), and preferably a combination of any two or more.

  The fluorescent particles of the present invention have afterglow characteristics.

Here, the material of the fluorescent particles is not limited to Sr ₂ MgSi ₂ O ₇ : Er, Dy, SrAl ₂ O ₄ : Eu, Dy, SrAl ₂ O ₄ : Eu, Sr ₄ Al ₁₄ O ₂₅ : Eu, Dy, Ca ₂ Al ₂ SiO ₇ : Ce, CaAl ₂ O ₄ : Eu, Nd, Lu ₂ SiO ₅ : Ce, ZnS: Cu, CaSrS: Bi, CaS: Eu, Tm, Moreover, it is preferable that they are any 2 or more types of combination. Moreover, although not necessarily limited, it is preferable that an average particle diameter exists in the range of 5-200 nm. In addition, the fluorescent particles used for bioimaging, which are not limited, are solutions that emit visible light from the fluorescent particles by irradiating the solution containing the fluorescent particles with excitation light to emit visible light. Is preferably administered into a living body, and the fluorescent particles are taken into a target site. Further, although not limited thereto, a fluorescent particle used for cancer treatment, in which a photosensitizer is administered into a living body, the photosensitizer is taken into cancer cells, and the solution contains the fluorescent particle. The fluorescent particles are irradiated with excitation light to cause visible light to be emitted, and a solution that emits visible light is administered into a living body so that the fluorescent particles are taken into the cancer cells and accumulated in the cancer cells. It is preferable to use a photosensitive substance and the fluorescent particles to generate active oxygen by a photochemical reaction and kill the cancer cells. In addition, but not limited to, fluorescent particles used for bio-imaging, and a primary antibody is joined to a tissue having an antigen, a secondary antibody joined to the fluorescent particles is joined to the primary antibody, It is preferable to block the excitation light after irradiating the tissue with excitation light and observe the emission of the fluorescent particles after the autofluorescence of the tissue disappears.

  The present invention has the following effects.

  The fluorescent particle manufacturing method of the present invention is a fluorescent particle manufacturing method in which a target in a liquid is irradiated with laser light. Since the target is made of a fluorescent material having afterglow characteristics, a novel fluorescent particle manufacturing method is provided. Can be provided.

  Since the fluorescent particles of the present invention have afterglow characteristics, novel fluorescent particles can be provided.

It is the schematic of the apparatus used in the Example. It is a figure which shows the SEM image of the produced fluorescent particle. It is a figure which shows a fluorescence spectrum (excitation wavelength 280nm). It is a figure which shows the data (excitation wavelength 280nm, fluorescence wavelength 465nm) of the time change of fluorescence intensity. It is a figure explaining the bioimaging without autofluorescence using the fluorescent nanoparticle which has an afterglow characteristic.

  Hereinafter, the form for implementing invention concerning fluorescent particle and its manufacturing method is explained.

A method for producing fluorescent particles will be described.
The method for producing fluorescent particles is a method in which the target in liquid is irradiated with laser light, and the target is made of a fluorescent material having afterglow characteristics.

Target materials include Sr ₂ MgSi ₂ O ₇ : Er, Dy, SrAl ₂ O ₄ : Eu, Dy, SrAl ₂ O ₄ : Eu, Sr ₄ Al ₁₄ O ₂₅ : Eu, Dy, Ca ₂ Al ₂ SiO ₇ : Ce, CaAl ₂ O ₄ : Eu, Nd, Lu ₂ SiO ₅ : Ce, ZnS: Cu, CaSrS: Bi, CaS: Eu, Tm, etc. Two or more combinations can be employed.

  As the laser, a solid laser, a gas laser, a semiconductor laser, or the like can be used.

  The standard of the wavelength of the laser to be used is that ultraviolet light having a wavelength of 400 nm or less is generally used because it is easy to ablate if it has absorption with respect to the target. Absorption is also possible, so ablation is possible even with long-wavelength laser light. Moreover, since the absorption edge of a substance changes with kinds of substance, the optimal wavelength changes with kinds of target to be used.

  The laser intensity used must be above the threshold that causes ablation. Since this value varies depending on the type of target, the method for producing the target, and the type of solvent, it is desirable that each value be optimal.

The laser oscillation method can be used not only for pulse oscillation but also for continuous oscillation if it has sufficient output.
The pulse width used has a significant effect on the threshold at which ablation occurs. This is because the peak value (peak value) changes even when the pulse has the same energy by changing the pulse width. When the pulse width is narrowed, the peak value increases.

  The higher the repetition frequency, the higher the amount of nanoparticles that can be produced per unit time.

  The diameter of the light beam at the focal position is closely related to the energy density for ablation. Even with lasers with the same energy per pulse, the energy density increases as the diameter of the light beam at the focal position decreases. In addition, the energy density decreases as the diameter of the light beam at the focal position increases. As a result, the diameter of the light beam at the focal position is a parameter for determining whether the ablation threshold is exceeded or not exceeded.

  The diameter of the light beam at the focal position is greatly related to the focal length of the lens to be arranged when the diameter of the light beam emitted from the laser is constant. As the focal length increases, the diameter of the light beam at the focal position increases, and as the focal distance decreases, the diameter of the light beam at the focal position also decreases. This value can be calculated geometrically.

  The longer the laser irradiation time, the greater the amount of nanoparticles that can be produced. The irradiation time and the production amount of nanoparticles are in a substantially proportional relationship, and many nanoparticles can be obtained by increasing the time.

  As the liquid, any one of polar solvents such as pure water, methanol, ethanol, and propanol, and nonpolar solvents such as hexane and benzene, or a combination of any two or more thereof can be used.

  Examples of liquid additives include anionic surfactants such as sodium dodecyl sulfate (SDS), cationic surfactants such as cetyltrimethylammonium bromide (CTAB), amphoteric surfactants such as alkylcarboxybetaine, polyethylene glycol ( Any one of nonionic surfactants such as PEG) and polyvinylpyrrolidone (PVP), or any combination of two or more thereof can be employed.

  By adding these additives, the fluorescence intensity increases, and at the same time, the decay of the fluorescence intensity per unit time is reduced, and the afterglow characteristics are improved. Also, dispersibility is improved by selecting an appropriate additive.

The fluorescent particles will be described.
The fluorescent particles have afterglow characteristics.

The material of the fluorescent particles is Sr ₂ MgSi ₂ O ₇ : Er, Dy, SrAl ₂ O ₄ : Eu, Dy, SrAl ₂ O ₄ : Eu, Sr ₄ Al ₁₄ O ₂₅ : Eu, Dy, Ca ₂ Al ₂ SiO ₇ : Ce, CaAl ₂ O ₄ : Eu, Nd, Lu ₂ SiO ₅ : Ce, ZnS: Cu, CaSrS: Bi, CaS: Eu, Tm, etc., any one of fluorescent materials having afterglow characteristics, Any two or more combinations can be employed.

  The shape of the fluorescent particles includes a sphere, an ellipsoid, and a rod.

  The average particle size of the fluorescent particles is preferably in the range of 5 to 200 nm. In vivo, fine particles of 200 nm or more are phagocytosed and accumulated in the liver and spleen by Kupffer cells of reticuloendothelial tissue. For this reason, when using fine particles in a living body, it is necessary to use 200 nm or less. In addition, fine particles of 5 nm or less are discharged from the body by the kidneys. For this reason, when using fine particles in a living body, it is necessary to set the thickness to 5 nm or more. These are known as EPR (Enhanced Permeability and Retention effect). The particles obtained by this method have a particle size distribution, but if necessary, only the desired particle size can be extracted and used by centrifugation, dialysis or the like.

  The afterglow characteristics of fluorescent particles can be evaluated by the slope of a log-log graph of time-fluorescence intensity, and usually have a negative value. The smaller this value, the longer the afterglow. In the present invention, it is remarkably improved by adding a surfactant, and various uses are expanded.

The fluorescent particles can be used for the following applications.
The application to the bioimaging method will be described. A solution containing fluorescent particles produced by this method is irradiated with strong excitation light such as ultraviolet light for a sufficient time. Thereby, the fluorescent particles having afterglow characteristics continue to emit visible light without being irradiated with ultraviolet light that is excitation light. This solution that emits light with visible light is administered in vivo. Administration methods include radial respiratory administration, oral administration, oral, sublingual and intranasal administration, TTS (transdermal therapeutic system) via the skin, subcutaneous injection, intramuscular injection, and local administration. In this case, in addition to a drug delivery system (DDS) based on passive targeting to a target site, active targeting using an antibody such as a monoclonal antibody, a peptide, a magnetic nanoparticle, or the like can be used. Thereby, bioimaging is possible as it is without exciting ultraviolet light excitation.

  In addition, bioimaging without autofluorescence can be performed using fluorescent particles having afterglow characteristics. For example, an immunohistochemical staining method can be used. That is, a primary antibody is joined to a tissue having an antigen, a secondary antibody joined to the fluorescent particles is joined to the primary antibody, and the excitation light is blocked after the tissue is irradiated with excitation light. The emission of the fluorescent particles can be observed after the autofluorescence of the tissue has disappeared. When the excitation light is blocked, the autofluorescence of the tissue disappears in about several seconds, whereas the fluorescent particles having afterglow characteristics of the present invention continue to emit light for several seconds. For this reason, a clear bioimaging image can be observed when observed after several seconds. In addition, although the example of the immunohistochemical staining method was demonstrated here, it is not limited to this method, It can also use for another general imaging method.

  The use for cancer treatment methods will be described. First, a photosensitive substance such as porphyrin is administered in vivo. Since cancer cells are actively dividing, porphyrins and the like tend to be taken up passively. Next, strong excitation light such as ultraviolet light is irradiated for a sufficient time to the solution containing the fluorescent particles produced by this method. Thereby, the fluorescent particles having afterglow characteristics continue to emit visible light without being irradiated with ultraviolet light that is excitation light. This solution that emits light with visible light is administered in vivo. Administration methods include radial respiratory administration, oral administration, oral, sublingual and intranasal administration, TTS (transdermal therapeutic system) via the skin, subcutaneous injection, intramuscular injection, and local administration. Fluorescent particles tend to be taken up passively by actively dividing cancer cells. In addition, fluorescent particles can be effectively transported to cancer cells using active targeting using antibodies such as monoclonal antibodies, peptides, magnetic nanoparticles, and the like. As a result, a photosensitizer and afterglow characteristic fluorescent particles that emit light are accumulated in cancer cells that are tumor tissues, where active oxygen is generated by a photochemical reaction, and the cancer cells are killed.

Usually, the combination of the absorption wavelength of the photosensitive substance and the fluorescence wavelength of the afterglow characteristic fluorescent particles is used, but if they do not match, the color conversion material can be used together. For example, in this case, when the absorption wavelength of the photosensitive substance is red and the fluorescence wavelength of the afterglow characteristic fluorescent particles is blue, active oxygen is generated by using a color conversion material that emits red using blue light as excitation light. This color conversion material is a Casun phosphor (CaAlSiN ₃ : Eu), nitridosilicate (Eu ₂ Si ₅ N ₈ , Ba ₂ Si ₅ N ₈ : Eu), sulfide (CaS: Eu ²⁺ , SrS: Eu ^{2 +} ), YAG: Ce ³⁺ (Y ₃ Al ₅ O ₁₂ ), silicate (Sr ₂ SiO ₄ : Eu ²⁺ ), complex thiometallate (CaGaS ₄ : Eu ³⁺ ), α sialon (Ca (Si, Al ) ₁₂ (N, O) ₁₆ : Eu) etc. When these are water-soluble, water-resistant coating with an inorganic material such as silica or an organic material such as PEG is required.

  It is to be noted that the present invention is not limited to the embodiment for carrying out the above-described invention, and various other configurations can be adopted without departing from the gist of the present invention.

  Next, specific examples of the present invention will be described. However, it goes without saying that the present invention is not limited to these examples.

<Preparation of sample>

a) Preparation of target Sr ₂ MgSi ₂ O ₇ : Eu ²⁺ , Dy ³⁺ (made by Kasei Optonics Co., Ltd., P170NB) was used as the raw material powder for the target. The target was fabricated by spark plasma sintering (SPS), in which voltage was applied while pressing from above. The conditions of the spark plasma sintering method (SPS) were a temperature of 1100 ° C., a pressure of 50 MPa, and a sintering time of 10 minutes. The pellet size was 15 mm in diameter and 5 mm in thickness. )

b) Laser ablation Example 1
In the apparatus schematic diagram of FIG. 1, a light beam 2 oscillated from a laser 1 is folded back by a mirror 3 arranged at a desired position, and condensed to a diameter of 1 mm by a plano-convex lens 4 having a focal length of 100 mm. Liquid phase laser ablation is performed by placing a target 7 in a quartz cell containing a solvent at this focal position. The condensed pulsed laser beam has high energy, and nanoparticles can be produced from the target 7. Pure water was used as a solvent, and 1 g / liter of polyethylene glycol (manufactured by Kanto Chemical Co., Inc., polyethylene glycol 2000, molecular weight 2000) was added as an additive. Laser ablation is performed at room temperature, and the temperature of the solvent is also room temperature. Although the irradiation time was 3 hours, the production amount of nanoparticles can be increased by increasing the irradiation time. The laser used was an Nd: YAG 3rd harmonic solid-state laser (EXPLA PL2143C, pulse oscillation, pulse width 25 ps, oscillation wavelength 355 nm, repetition frequency 10 Hz, 60 mW, 6 mJ / pulse).

Example 2
Same as Example 1 except that no polyethylene glycol was added.

Example 3
The same as Example 1 except that a KrF excimer laser (LPX manufactured by Lambda Physik, pulse oscillation, pulse width 20 ns, oscillation wavelength 248 nm, repetition frequency 10 Hz, 2 W, 200 mJ / pulse) was used as the laser.

Example 4
Example 1 except that an Nd: YAG triple wave solid-state laser (JDSU M210S, pulse oscillation, pulse width 20 ns, oscillation wavelength 248 nm, repetition frequency 10 kHz, 5 W, 0.5 mJ / pulse) was used as the laser. It is the same.

  <Evaluation method>

a) Shape, average particle size The shape and size of the particles were measured with a scanning electron microscope (Hitachi High-Technologies, S-4800) obtained by drying the solvent containing the produced nanoparticles.

b) Fluorescence spectrum The fluorescence spectrum was measured with a fluorescence spectrophotometer (Hitachi High-Technologies, F-7000) after placing the solvent containing the prepared nanoparticles in a quartz cell.

c) Fluorescence afterglow characteristics Fluorescence afterglow characteristics were measured with a fluorescence spectrophotometer (Hitachi High-Technologies, F-7000) by placing the solvent containing the prepared nanoparticles in a quartz cell. )

  <Evaluation results>

a) Shape and average particle diameter Generally, particles having a size distribution are produced by the laser ablation method. In Example 1, particles having a size of several to several 100 nm were formed as shown in FIG. The average particle size was approximately 100 nm. The shape was mainly spherical. In other Examples 2 to 4, substantially the same ones were produced.

b) Fluorescence spectrum The particles dispersed in the solution showed a broad blue emission due to the 5d → 4f transition of Eu ²⁺ with a peak around 465 nm, the same as the target. The produced particles seem to maintain the same composition as the target.

  FIG. 3 shows data of fluorescence spectra (excitation wavelength 280 nm) when the surfactant (polyethylene glycol) is present during laser ablation (Example 1) and when it is not (Example 2). By adding a surfactant, the surfactant seems to coat the nanoparticles. This protects surface defects on the surface of the nanoparticle, and it is considered that the fluorescence characteristics are improved by the disappearance of the defect level.

c) Fluorescence afterglow characteristics Data of changes in fluorescence intensity over time (excitation wavelength: 280 nm, fluorescence, when surfactant (polyethylene glycol) is present during laser ablation (Example 1) and not (Example 2) FIG. 4 shows the wavelength (465 nm). By adding a surfactant, the surfactant seems to coat the nanoparticles. Thus, the surface defects on the nanoparticle surface are protected, and the afterglow characteristics are expected to be improved by the disappearance of the defect level.

Example 5
Bioimaging without autofluorescence using fluorescent nanoparticles having afterglow characteristics produced by the above method will be described with reference to FIG.
The tissue to be observed embedded in formalin-fixed paraffin is made into a tissue section 8 of about 3 to 5 μm with a microtome or the like. This is heated in an oven at about 58 ° C., soaked in xylene, then soaked in absolute ethanol, washed with water, and soaked in phosphate buffered saline (PBS) to remove paraffin. If the tissue is difficult to stain, the antigen (protein) 9 is exposed by performing enzyme recovery, microwave recovery, or the like. On the other hand, 100 μl of diluted primary antibody 10 is dropped to cover the tissue section 8, incubated at 37 ° C. for 60 minutes in a humidified chamber, washed with PBS, and then washed with water. Next, the secondary antibody 12 conjugated with fluorescent nanoparticles 11 having afterglow characteristics is diluted, dropped onto a 100 μl tissue section 8, covered, incubated in a humidified chamber at 37 ° C. for 60 minutes, and immersed in a PBS bath. . The tissue section 8 of this sample is observed with a fluorescence microscope.

  Normally, when the excitation light is irradiated, the tissue section 8 emits light due to autofluorescence, and the emission of the fluorescent marker cannot be confirmed. However, when the excitation light is blocked, the autofluorescence of the tissue section 8 and the normal fluorescent marker disappears in about several seconds, whereas the fluorescent nanoparticles 11 having the afterglow characteristics of the present invention Continue to fire for a few seconds. For this reason, a clear bioimaging image observation becomes possible when observed after several seconds.

DESCRIPTION OF SYMBOLS 1 ... Laser, 2 ... Light, 3 ... Mirror, 4 ... Lens, 5 ... Solvent, 6 ... Nanoparticle, 7 ... Target, 8 ... Tissue section, 9 ... Antigen (protein), 10 ... primary antibody, 11 ... fluorescent nanoparticles, 12 ... secondary antibody, 13 ... slide glass

Claims (17)

In the method for producing fluorescent particles, in which a target in liquid is irradiated with laser light,
The method for producing fluorescent particles, wherein the target is made of a fluorescent material having afterglow characteristics. The target material is Sr ₂ MgSi ₂ O ₇ : Er, Dy, SrAl ₂ O ₄ : Eu, Dy, SrAl ₂ O ₄ : Eu, Sr ₄ Al ₁₄ O ₂₅ : Eu, Dy, Ca ₂ Al ₂ SiO ₇ : Ce, CaAl ₂ O ₄ : Eu, Nd, Lu ₂ SiO ₅ : Ce, ZnS: Cu, CaSrS: Bi, CaS: Eu, Tm, and any combination of two or more The method for producing a fluorescent particle according to claim 1, wherein The method for producing fluorescent particles according to claim 1, wherein the target material is Sr ₂ MgSi ₂ O ₇ : Er, Dy. The liquid is any one of a polar solvent such as pure water, methanol, ethanol and propanol, and a nonpolar solvent such as hexane and benzene, or a combination of any two or more thereof. A method for producing fluorescent particles. The method for producing fluorescent particles according to claim 1, wherein the liquid is pure water. What is added to the liquid is an anionic surfactant such as sodium dodecyl sulfate (SDS), a cationic surfactant such as cetyltrimethylammonium bromide (CTAB), an amphoteric surfactant such as alkylcarboxybetaine, polyethylene glycol (PEG ), A nonionic surfactant such as polyvinylpyrrolidone (PVP), or a combination of any two or more thereof. The method for producing fluorescent particles according to claim 1. The method for producing fluorescent particles according to claim 1, wherein what is added to the liquid is polyethylene glycol (PEG). The target material is Sr ₂ MgSi ₂ O ₇ : Er, Dy,
The method for producing fluorescent particles according to claim 1, wherein the liquid is pure water. The target material is Sr ₂ MgSi ₂ O ₇ : Er, Dy,
The liquid is pure water
The method for producing fluorescent particles according to claim 1, wherein what is added to the liquid is polyethylene glycol (PEG). A fluorescent particle characterized by having afterglow characteristics. The materials of the fluorescent particles are Sr ₂ MgSi ₂ O ₇ : Er, Dy, SrAl ₂ O ₄ : Eu, Dy, SrAl ₂ O ₄ : Eu, Sr ₄ Al ₁₄ O ₂₅ : Eu, Dy, Ca ₂ Al ₂ SiO ₇ : Ce, CaAl ₂ O ₄ : Eu, Nd, Lu ₂ SiO ₅ : Ce, ZnS: Cu, CaSrS: Bi, CaS: Eu, Tm Any one or a combination of two or more The fluorescent particle according to claim 10. The fluorescent particle according to claim 10, wherein the material of the fluorescent particle is Sr ₂ MgSi ₂ O ₇ : Er, Dy. The fluorescent particles according to claim 10, wherein the average particle size is in the range of 5 to 200 nm. The material of the fluorescent particles is Sr ₂ MgSi ₂ O ₇ : Er, Dy,
The fluorescent particles according to claim 10, wherein the average particle size is in the range of 5 to 200 nm. Fluorescent particles used for bioimaging,
Irradiating excitation light to the solution containing the fluorescent particles to emit visible light from the fluorescent particles,
The fluorescent particle according to claim 10, wherein a solution that emits visible light is administered into a living body, and the fluorescent particle is taken into a target site. Fluorescent particles used for cancer treatment,
Administering a photosensitizer into the living body, causing the cancer cells to incorporate the photosensitizer,
Irradiating excitation light to the solution containing the fluorescent particles to emit visible light from the fluorescent particles,
A solution that emits visible light is administered into a living body, and the fluorescent particles are taken into the cancer cells.
The fluorescent particles according to claim 10, wherein the photosensitizer accumulated in the cancer cells and the fluorescent particles are used to generate active oxygen by a photochemical reaction to kill the cancer cells. Fluorescent particles used for bioimaging,
A primary antibody is conjugated to a tissue having an antigen;
A secondary antibody conjugated with the fluorescent particles is conjugated to the primary antibody,
Blocking the excitation light after irradiating the tissue with excitation light,
The fluorescent particles according to claim 10, wherein light emission of the fluorescent particles is observed after the autofluorescence of the tissue disappears.

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