KR20120007392A - Aqueous dispersion of near-infrared photothermal organic nanoparticles, and preparation method and use thereof - Google Patents

Abstract

PURPOSE: Aqueous dispersed near-infrared photothermal organic nanoparticles, and a preparation method and a use thereof are provided to obtain superior biocompatibility and photothermal effects by using biocompatible surfactant and densely containing a photothermal organic pigment. CONSTITUTION: Aqueous dispersed near-infrared photothermal organic nanoparticles include cores, surfactants, and water. The cores contain hydrophobic photothermal organic materials. The surfactants surround the cores. The contents of the organic materials, the surfactants, and water are respectively between 0.01 and 3 weight%, between 0.1 and 30 weight%, and between 70 and 99.89 weight% based on the total weight of the aqueous dispersed chemically luminescent particles. The absorption wavelength of the organic materials is in a range between 600 and 900nm. The organic materials are one or more selected from a group including cyanine and phtalocyanine. The organic materials and the surfactants are dissolved in an organic solvent, and the organic solvent is eliminated. The product of the dissolution is dispersed in water.

Description

Aqueous Dispersion Near Infrared Photothermal Organic Nanoparticles and Method for Use and Manufacturing Method Thereof {AQUEOUS DISPERSION OF NEAR-INFRARED PHOTOTHERMAL ORGANIC NANOPARTICLES, AND PREPARATION METHOD AND USE THEREOF}

In the present invention, nanoparticles containing photothermal organic dyes that absorb light in the near-infrared region and generate high heat are accumulated in cancer tissues in vivo and light heat is generated to destroy cancer cells by generating high heat by irradiating light. The present invention relates to a water-dispersible photothermal organic nanoparticles capable of cancer treatment by therapy, and to a method and a use thereof.

Hyperthermia therapy has been used to treat various diseases such as infections and inflammations by exposing body tissues to high temperatures (about 41 ° C or less) to enhance impurities release and immunity in the body.

In particular, unlike normal cells that release heat through blood vessels when the temperature in the body rises above about 41 ° C, cancer cells are not easily discharged and are susceptible to direct thermal damage and are more sensitive to radiation or anticancer drugs. The effect is increased.

Hyperthermia is performed through various methods such as radiation therapy, chemotherapy, biotherapy, and local fever using ultrasound to enhance the effect. High frequency is used to heat some areas from the outside, heated thin wires for internal heating, tubes filled with hot water, implanted microwave antennas, and radio wave electrodes are used. Local hyperthermia for ultrasound-based tumors has the advantage of being easier to focus than other energy delivery methods.

These high fever therapies do not cause any particular side effects, but if the fever comes in direct contact with the skin, it can cause discomfort, severe local pain, blisters, etc., and very often burns in about half of the patients. .

Near-infrared photothermal therapy absorbs light in the near-infrared region and accumulates heat-generating material in a location requiring hyperthermia, and irradiates and treats near-infrared light. Therefore, local treatment in vivo is made as deep as possible and damage to other tissues is minimized except where the substance is accumulated.

Using the light-heat substance Examples of the near infrared light-heat treatment of cancer in a living body, metals and inorganic nano-material, the gold nano-rods (gold nanorod0 [Document 1] EB Dickerson et al, Cancer Letters 269: 57-66 (2008)], gold nanoshells [Document 2: DP O'Neal et al., Cancer Letters 209: 171-176 (2004), Document 3: AM Gobin et al., Nano Letters 7: 1929-1934 (2007)], carbon nanotubes [Document 4: S Ghoshy et al., ACS Nano 3: 2667-2673 (2009), Document 5: HK Moon et al., ACS Nano 3: 3707-3713] and indocyanine green as an organic dye [Document 6: WR Chen et al., Cancer Letters 94: 125-131 (1995), Document 7: WR Chen et al., Cancer Letters 98: 169-173 (1996), Document 8: WR Chen et al., Cancer Letters 115: 25-30 (1997)] are reported.

Among them, inorganic materials have their own toxicity problems and remaining in vivo. Only the organic dye indocianin green has been approved by the FDA for its high photothermal efficiency and low toxicity. However, indocyanine green is rapidly removed in vivo, and thus it is difficult to accumulate in cancer tissues through blood circulation. Therefore, only examples of direct treatment of cancer with cancer treatment have been reported. It is easy to get involved in death. In order to overcome this, in recent years, indocyanine green is adsorbed or encapsulated in micro-nano capsules to increase the retention time in vivo. Document 9: J. Yu et al . Chem . Mater . 19: 1277-1284 (2007)] Attempts to target specific cancer cells [10: R. Bardhan et al . , Adv . Funct. Mater . 19: 3901-3909 (2009). However, there is a limit to achieving high photothermal efficiency due to the low concentration of indocyanine green.

Effective photothermal treatment of cancer in vivo is easy to discharge in vivo, has low potential toxicity, utilizing drug delivery system, high accumulation efficiency and cancer cell targetability to target cancer tissue, high absorption coefficient and high exothermic efficiency The development of visible organic nanostructures is desired.

An object of the present invention is to solve the above-described problems of the prior art, to provide a material for photothermal therapy in which a high extinction coefficient, high exothermic efficiency and high cancer tissue accumulation efficiency are achieved. Specifically, the biocompatible photothermal nanoparticles exhibit high photothermal effect and effectively accumulate in cancer tissues by containing a high density of photothermal organic dye which absorbs light in the near infrared region and stays in the body for a long period of time. It is intended to provide a method for producing the same and a method of using the photothermal nanoparticles in the extinction of cancer cells in vivo or ex vivo.

The technical problem of the present invention is achieved by preparing photothermal nanoparticles including a biocompatible polymer and an organic dye exhibiting a photothermal effect, and inducing the disappearance of cancer cells by irradiating light in vivo or in vitro. Accordingly, the present invention relates to what is described below.

(1) (a) a core comprising a hydrophobic photothermal organic material,

(b) a surfactant surrounding the core,

(c) water

Containing, aqueous dispersion photothermal organic nanoparticles.

(2) The content of (a) the hydrophobic photothermal organic material, (b) the surfactant and (c) the water according to (1), (a) 0.01 to 3% by weight, respectively, based on the total weight of the aqueous dispersion chemiluminescent particles, (b) 0.1 to 30% by weight and (c) 70 to 99.89% by weight.

(3) The aqueous dispersion photothermal organic nanoparticles of (1), wherein the hydrophobic photothermal organic material has an absorption wavelength in the range of 600 to 900 nm.

(4) The aqueous dispersion light heat according to the above (3), wherein the hydrophobic photothermal organic material is selected from the group consisting of cyanine-based (Indyanine-based, thiaasianin-based, oxacyanine-based) and phthalocyanine-based. Organic nanoparticles.

(5) The hydrophobic photothermal organic material according to (3), wherein the hydrophobic photothermal organic material is iodide 1,1 ', 3,3,3', 3'-hexamethylindotricarbocyanine, 3,3'-diethyl iodide Aqueous dispersed photothermal organic nanoparticles selected from the group consisting of tiatricarbocyanine and 2,9,16,23-tetra- tert -butyl- 29H, 31H -phthalocyanine.

(6) The aqueous dispersion photothermal organic nanoparticles of (1), wherein the surfactant is a poloxamer.

(7) The method of (6), wherein the poloxamer is Pluronic ^® F 38, Pluronic ^® F 68, Pluronic ^® F 77, Pluronic ^® F 87, Pluronic ^® F 88, Flu Lonic ^® F 98, Pluronic ^® F 127, Pluronic ^® P 181 and Pluronic ^® P 407 is an aqueous dispersion of organic light-heat the nanoparticles is selected from the group consisting of.

(8) The aqueous dispersion photothermal organic nanoparticles according to (1), wherein the diameter is 10 to 200 nm.

(9) The aqueous dispersion photothermal organic nanoparticles according to any one of the above (1) to (8), which is used for high-temperature tea inside and outside the living body.

(10) The aqueous dispersion photothermal organic nanoparticles according to (9), wherein the hyperthermia treatment is performed on cancer tissues in vivo.

(11) (a) uniformly dissolving a hydrophobic photothermal organic material and a surfactant in an organic solvent, and then removing the organic solvent,

(b) dispersing the product of step (a) in water

A method of producing a water-based dispersed photothermal organic nanoparticles comprising a.

(12) The method according to (11), wherein the aqueous dispersion photothermal organic nanoparticles include a core containing a hydrophobic photothermal organic material, a surfactant surrounding the core, and water.

(13) The method according to (11) or (12), wherein the hydrophobic photothermal organic material has an absorption wavelength in the range of 600 to 900 nm.

(14) The production method according to the above (13), wherein the hydrophobic photothermal organic material is selected from the group consisting of cyanine (indocyanine-based, thiasianin-based, oxacyanine-based) and phthalocyanine-based.

(15) The hydrophobic photothermal organic material according to (14), wherein the hydrophobic photothermal organic material is iodide 1,1 ', 3,3,3', 3'-hexamethylindotricarbocyanine and iodide 3,3'-diethylthiatri Method for producing aqueous dispersion photothermal organic nanoparticles selected from carbocyanine

(16) The production method according to (11) or (12), wherein the surfactant is a poloxamer.

(17) The method of (16), wherein the poloxamer is Pluronic ^® F 38, Pluronic ^® F 68, Pluronic ^® F 77, Pluronic ^® F 87, Pluronic ^® F 88, Flu Lonic ^® F 98, The method for producing a fluorene will nick ^® F 127, which is selected from the group consisting of fluorene as a nick ^® P 181 and Pluronic ^® P 407.

(18) The production method according to (11) or (12), wherein the diameter of the aqueous dispersion photothermal organic nanoparticles is 10 to 200 nm.

(19) The production method according to (11), wherein the organic solvent in the step (a) is evaporated and removed at room temperature.

(20) The production method according to (11), wherein the organic solvent is selected from one or more selected from the group consisting of dichloromethane, tetrahydrofuran, chloroform, ethyl acetate, and methanol.

(21) The method according to the above (11), wherein the water in the step (b) is used 2 to 200 times with respect to the weight of the photothermal organic nanoparticles.

(22) (a) homogeneously mixing the hydrophobic photothermal organic material and the surfactant at a high temperature, followed by rapid cooling,

(b) dispersing the product of step (a) in water

A method of producing a water-based dispersed photothermal organic nanoparticles comprising a.

(23) The method according to (22), wherein the aqueous dispersion photothermal organic nanoparticles comprise a core comprising a hydrophobic photothermal organic material, a surfactant surrounding the core, and water.

(24) The method according to (22) or (23), wherein the hydrophobic photothermal organic material has an absorption wavelength in the range of 600 to 900 nm.

(25) The production method according to (24), wherein the hydrophobic photothermal organic material is selected from the group consisting of cyanine-based (indocyanine-based and thiasianin-based) and phthalocyanine-based.

(26) The method for producing the aqueous dispersion photothermal organic nanoparticles according to (25), wherein the hydrophobic photothermal organic material is 2,9,16,23-tetra- tert -butyl- 29H, 31H -phthalocyanine.

(27) The method according to (22) or (23), wherein the surfactant is a poloxamer.

(28) The method of (27), wherein the poloxamer is Pluronic ^® F 38, Pluronic ^® F 68, Pluronic ^® F 77, Pluronic ^® F 87, Pluronic ^® F 88, Flu Lonic ^® F 98, The method for producing a fluorene will nick ^® F 127, Pluronic ^® P 181 and fluorine as selected from the group consisting of Nick ^® P 407.

(29) The production method according to (22) or (23), wherein the diameter of the aqueous dispersion photothermal organic nanoparticles is 10 to 200 nm.

(30) The method according to the above (22), wherein the hydrophobic photothermal organic material and the surfactant in the step (a) are uniformly dispersed at 150 ° C.

(31) The process according to (22), wherein the rapid cooling in step (a) is performed in ice.

(32) The method according to the above (22), wherein the water in the step (b) is used 2 to 200 times by weight of the photothermal organic nanoparticles.

According to the present invention, nanoparticles containing photothermal organic materials that are easily released and decomposed in vitro can be efficiently accumulated in cancer tissues to effectively induce cell death of cancer tissues by photothermal effects when irradiating near-infrared rays with a long penetration depth. The biocompatible near-infrared photothermal organic nanoparticles, the preparation method thereof, and the nanoparticles can be used for killing cancer cells in vivo or ex vivo.

In addition, according to the present invention, in the state of containing a large amount of hydrophobic photothermal organic dye in the center of the nanoparticles, it is excellent in aqueous dispersion stability and medical applications of photothermal organic dyes widely used in information electronic materials by using a biocompatible polymer as a surfactant Nanoparticles can be effectively produced.

In addition, the aqueous dispersion of the near-infrared photothermal organic nanoparticles according to the present invention can be used for hyperthermia because it can heat the temperature of water to 47 ° C when irradiating near-infrared laser.

Since the near-infrared photothermal organic nanoparticles according to the present invention penetrate and accumulate well in cancer cells, it is possible to induce cell death by the photothermal effect in cancer cells, thereby selectively and effectively removing cancer tissues.

BRIEF DESCRIPTION OF THE DRAWINGS It is a schematic diagram of the structure of the photothermal organic nanoparticle ("NP") manufactured by the method as described in Example 1 (1) and (2) of this invention, and the photothermal phenomenon of the said particle | grain.
Figure 2 is a transmission electron microscope (TEM) photograph of the F- t BPC nanoparticles prepared in Example (2) of the present invention.
FIG. 3 shows the F-TC, F-IC, and F- t BPC nanoparticle aqueous dispersions prepared in (1) and (2) of Example 1 according to the method of Example 1 (3). It is a graph showing the change of dispersion temperature with the irradiation time when irradiated with a laser of 671 nm.
4 is irradiated with a laser to cancer cells (HeLa) embedded in the F- t BPC nanoparticles prepared in Example 1 (2) of the present invention for 12 hours according to the method shown in Example (1). It is a graph showing cell viability at time. The closed square (■) shows cell viability according to the nanoparticle concentration of the cell culture when irradiated with a laser of 671 nm for 10 minutes. Open circles (○) represent cell viability with laser irradiation time of cancer cells cultured at nanoparticle concentration of 1 mg / ml. Closed circles (●) indicate cell viability with laser irradiation time of cancer cells cultured in the cell culture without the nanoparticles.
FIG. 5 is an intravenous injection of F- t BPC nanoparticles prepared in Example 2 (2) of the present invention into a cancer model rat according to the method shown in Example 2 (1), and 13 days after laser irradiation for 20 minutes. A graph showing the change in cancer size. Triangle (Δ) represents a cancer model rat intravenously injected with 0.1 mL of aqueous dispersed nanoparticles at a concentration of 10 mg / mL, and circle (○) represents a cancer model rat (control) without injection of the nanoparticles.

The present invention,

(a) a nanoparticle core in which hydrophobic photothermal organic materials are accumulated at high density,

(b) a surfactant surrounding the core,

(c) water

It relates to a water-based dispersed photothermal organic nanoparticles.

Preferably, The content of the hydrophobic photothermal organic material is 0.01 to 3% by weight, the surfactant is 0.1 to 30% by weight, and the water is 70 to 99.89% by weight based on the total weight of the aqueous dispersion in which the photothermal organic nanoparticles are dispersed.

The hydrophobic photothermal organic material preferably has an absorption wavelength in the range of 650 to 900 nm in order to increase the depth reached by the laser. If the absorption wavelength is less than 650 nm, the laser wavelength is too short to penetrate deeply into the tissue, so only photothermal treatment is possible near the skin. If the absorption wavelength is longer than 900 nm, interference due to the absorption of excess water in the living body is prevented. It is not desirable because it increases.

The hydrophobic near-infrared photothermal organic material includes a photothermal dye having a high absorbance in the near-infrared region due to its long conjugated length of pi ( p ) electrons in order to obtain a high-efficiency photothermal effect. Preferably, the photothermal dye is cyanine-based (Indyanine-based (IR-676, IR-775, IR-780, IR-786, IR-792, IR-797, IR-800, etc.), thiasianin (IR-140, etc.) and phthalocyanine series (phthalocyanine series, cupperphthalocyanine series, zinc phthalocyanine series, silicon phthalocyanine series, iron phthalocyanine series, cobalt cyanine series, dilithium cyanine series, disodium cyanine series, etc.) At least one selected from the group consisting of.

Since the hydrophobic dye is insoluble in water, it is possible to form aggregates in water by itself, and thus it is possible to accumulate at a higher density than hydrophilic dyes. Accordingly, the core in which the near-infrared photothermal organic dye is accumulated at a high density increases the absorbance of the photothermal nanoparticles and provides light stability to overcome the low absorbance and unnecessary photobleaching, which are limitations of the conventional photothermal organic dyes. To provide.

This means that when a large amount of dye is accumulated, the number of absorbing light increases, so that the absorbance is increased, and even though some molecules are discolored by light, many molecules are stably maintained to have overall photobleaching resistance. In other words, this feature is also advantageous compared to the nanoparticles using a hydrophilic dye.

The surfactant serves as both a surfactant and a support for maintaining the structure of the core including the hydrophobic photothermal organic material, and is preferably a biocompatible surfactant for dispersion stability and suitability in a physiological environment.

Accordingly, the surfactant is a poloxamer family of surfactants widely used in drug delivery systems and hydrogels. Specifically, Pluronic ^® F 38, Pluronic ^® F 68, Pluronic ^® F 77, Pluronic ^® F 87, Pluronic ^® F 88, Pluronic ^® F 98, Pluronic ^® F 127, Pluronic ^® P 181 and Pluronic ^® P 407 (manufactured by BASF).

To the poloxamers, in particular Pluronic ^® F-127 and F-68, so forming micelles (micelle) or hydrogel, a material commonly used as a delivery system of drugs or contrast agents for molecular imaging in uiyakhak field. Proxamers, like other surfactants, have a hydrophilic and hydrophobic moiety attached to two molecules, forming a micelle structure in which the hydrophobic moiety is concentrated in the center and the hydrophilic moiety surrounds the outside. Therefore, since the center of the nanostructure becomes relatively hydrophobic, it is easy to contain hydrophobic photothermal organic materials, and the surface is surrounded by polyethylene glycol (PEG) having hydrophilicity and antifouling effect so that the nanoparticles are stable for a long time in the blood. By circulating to the EPR (Enhanced Permeation and Retention) effect can increase the efficiency of rock accumulation (癌 蓄積).

The diameter of the aqueous dispersion near-infrared photothermal organic nanoparticles according to the invention is 5 to 500 nm, preferably 10 to 200 nm. This is because the nanoparticles are suitable for clinical and diagnostic purposes when they are within this diameter range. Document 11: D. Peer et al., Nature Nanotech . 2: 751-760 (2007).

The present invention also relates to a high thermal therapeutic use comprising the aqueous dispersion near infrared photothermal organic nanoparticles.

The photothermal effect of the aqueous dispersion near-infrared photothermal organic nanoparticles according to the present invention was confirmed by measuring the fact that when the laser dispersion is irradiated to the aqueous dispersion nanoparticles, the temperature is raised to 41 ° C or higher suitable for photothermal treatment.

Therefore, when the nanoparticles are injected into the living body, since they are effectively accumulated in the cancerous region, the local temperature can be increased through laser irradiation, thereby enabling high-temperature treatment of the affected area, and at the same time minimizing damage to the normal region.

In addition, the present invention relates to a method for producing the aqueous dispersion photothermal organic nanoparticles, which method,

(a) dissolving the hydrophobic photothermal organic material and the surfactant in an organic solvent, and then removing the organic solvent to uniformly fix the mixture, or

(b) uniformly mixing the hydrophobic photothermal organic material and the surfactant at a high temperature and then rapidly cooling to fix the mixture,

(c) adding water to the product of step (a) or (b) to form an aqueous dispersion of nanoparticles consisting of a hydrophobic photothermal organic material and a surfactant.

The organic solvent of step (a) is at least one selected from the group consisting of dichloromethane, tetrahydrofuran, chloroform, ethyl acetate and methanol. These organic solvents are preferably removed by evaporation at room temperature.

The water in step (c) is preferably distilled water. The amount of water is suitably 2 to 200 times the total weight of the aqueous dispersion photothermal organic nanoparticles.

Example

Hereinafter, the present invention will be described in more detail with reference to Examples. However, these examples are for illustrating the present invention, and the scope of the present invention is not limited only to these examples.

Example  One: Near infrared Heat  Preparation of organic nanoparticles and Heat  Property evaluation

(One) Heat  Organic Nanoparticles (F- IC  And F- TC Manufacturing

Pluronic ^{® F-127 (BASF) 1} mg with the Pluronic ^® F-127 with respect to iodide 1,1 ', 3,3,3', 3'-hexamethyl-Indian tree, not during carbonyl (IC , Available from Aldrich) or 0.1 mg of 3,3'-diethylthiatricarbocyanine iodide (TC, available from Aldrich) is dissolved in 0.2 mL of dichloromethane, mixed uniformly, and the solvent is evaporated at room temperature. Removed.

Then, 1 mL of distilled water was added and uniformly mixed to obtain aqueous dispersed nanoparticles (F-IC) in which IC was accumulated at the center, that is, cores, or aqueous dispersed nanoparticles (F-TC) in which TC was accumulated. 1 is a schematic view of the structure of the nanoparticles obtained by performing the above method and a photothermal phenomenon of the nanoparticles.

(2) Heat  Organic Nanoparticles (F- t BPC Manufacturing

100 mg of polyethylene glycol 400 (PEG 400, Fluka) and 25 mg of 2,9,16,23-tetra- tert -butyl- 29H, 31H -phthalocyanine ( t BPC, available from Aldrich) were introduced into the reaction vessel for 30 minutes. after stirring and uniformly dispersed to prepare a flu in the vessel, introducing 400 mg Nick ^® F-68 (BASF) and the mixture was stirred for 1 hour and 30 minutes at 150 ° C.

Stopping the heating and then rapidly cooling the reaction vessel by ice, added distilled water to 1 mL to obtain a dispersion mixture of 2 mg, and mixed uniformly in the center, that is, t BPC core accumulated water dispersing nanoparticles (F t BPC). 1 is a schematic view of the structure of the nanoparticles obtained by the above method and a photothermal phenomenon of the nanoparticles.

(3) Heat  Particle characteristics of organic nanoparticles and Heat  Property evaluation

The shape and size of the nanoparticles prepared in (2) and the diffraction pattern were observed in a transmission electron microscope (CM30, FEI / Philips, 200 kV) and are shown in FIG. 2. It can be seen from FIG. 2 that the nanoparticles prepared in (2) are spherical particles having a diameter of 30 nm or less and are crystalline.

In order to evaluate the photothermal characteristics of the nanoparticles prepared in (1) and (2), F-IC and F-PC at 1.1 mg / mL concentration and F- t BPC at 2 mg / mL concentration (photothermal dye content: Each 0.1 mg) 0.1 mL aqueous dispersion was introduced into a UV measuring cuvette and the temperature change over time was measured while irradiating a 671 nm laser (SDL-671-200T, Shanghai Dream Lasers, China).

As shown in FIG. 3, the temperature increase was hardly observed in the water without the nanoparticles, but the increase in temperature may be observed in the aqueous dispersion nanoparticles. The F-TC aqueous dispersion can be seen to increase in temperature with laser irradiation time, but the increase in temperature is small compared to the other two aqueous dispersion nanoparticles. However, the F-TC aqueous dispersion does not cause photobleaching. The F-IC aqueous dispersions increase in temperature very rapidly, increasing to more than 41 ° C. after 1 minute and 30 seconds, but after 3 minutes the temperature is lowering, which is responsible for the occurrence of photobleaching. The F- t BPC showed a temperature increase of more than 41 ° C after 3 minutes and 30 seconds of laser irradiation, and a steady increase in temperature even after 13 minutes, and no photobleaching.

Example  2: Evaluation of Cytotoxicity and In Vivo Cancer Treatment Characteristics

(1) Cytotoxicity Assessment

The aqueous dispersed F- t BPC nanoparticles prepared in (3) of Example 1 were added to a living cancer cell (HeLa cell) culture medium, and embedded in the cells for 12 hours. After the laser irradiation with respect to the cells containing the nanoparticles and the cells not containing the nanoparticles, it is shown in Figure 4 by comparing the cell survival rate according to the laser irradiation time and nanoparticle concentration.

When cells containing various concentrations of aqueous dispersed F-tBPC nanoparticles were irradiated with a 671 nm laser (SDL-671-200T, Shanghai Dream Lasers, China) for 10 minutes, the cell viability increased as the concentration of the nanoparticles increased. It was confirmed that is lowered. As a result of fixing the concentration of the nanoparticles to 1 mg / mL and observing the cell viability according to the laser irradiation time, the cell viability was lowered according to the irradiation time, and when the irradiation was performed for 20 minutes, the viability was reduced to about 40%. It was. On the contrary, the cells not containing the nanoparticles were maintained at 100% cell viability until 15 minutes depending on the laser irradiation time, and decreased to about 80% after 20 minutes irradiation.

According to the above results, it was confirmed that the aqueous dispersion F- t BPC nanoparticles are toxic to cancer cells when irradiated with laser, which is proportional to the irradiation time and the concentration of nanoparticles, and thus the nanoparticles can be used for cancer cell death. Has been confirmed.

(2) In vivo  Evaluation of cancer treatment characteristics

In order to conduct an animal cancer treatment experiment, 1 × 10 ⁶ SCC7 (Squamous Cell Carcinoma) cells were injected subcutaneously into the left hip muscle area of a male rat (BALB / c, 5 weeks old, Institute of Medical Science, Tokyo).

Two weeks later, 0.1 mL of 10 mg / mL aqueous dispersion F-tBPC nanoparticles were injected into the tail vein of the anesthetized male rat, and after 7 hours, the cancer tissue was irradiated with 671 nm laser for 20 minutes to observe the size of the cancer for 13 days. . For the control experiment, the control group not injected with the nanoparticles was also irradiated with a laser for 20 minutes and observed the size of the cancer for 13 days, and the results are shown in FIG. 5.

From Figure 5, it can be seen that the aqueous dispersion of the F- t BPC particles according to the present invention significantly slows the growth of cancer cells when irradiated with a laser after intravenous injection. Therefore, it was confirmed that the near-infrared photothermal organic nanoparticles F- t BPC of the present invention can be used for effective cancer tissue removal with a local photo-thermal therapy (PTT) during hyperthermia for cancer treatment.

Claims (32)

(a) a core comprising a hydrophobic photothermal organic material,
(b) a surfactant surrounding the core,
(c) water
Aqueous dispersing photothermal organic nanoparticles, including. The method of claim 1, wherein the content of (a) hydrophobic photothermal organic material, (b) surfactant, and (c) water is respectively (a) 0.01 to 3% by weight, (b) 0.1 based on the total weight of the aqueous dispersed chemiluminescent particles. To 30% by weight and (c) 70 to 99.89% by weight. According to claim 1, wherein the hydrophobic photothermal organic material is water-dispersible photothermal organic nanoparticles having an absorption wavelength range from 600 to 900 nm. According to claim 3, The hydrophobic light-thermal organic material is water-based dispersed light-heat organic nanoparticles are selected from the group consisting of cyanine (indyanine-based, thiasianin-based, oxacyanine-based) and phthalocyanine-based. The method of claim 3, wherein the hydrophobic photothermal organic material is iodide 1,1 ', 3,3,3', 3'-hexamethyl indotricarbocyanine, iodide 3,3'-diethylthiatricarbosi And 2,9,16,23-tetra- tert -butyl- 29H, 31H -phthalocyanine. The aqueous dispersion photothermal organic nanoparticles of claim 1, wherein the surfactant is a poloxamer. The method of claim 6, wherein the poloxamer is Pluronic ^® F 38, Pluronic ^® F 68, Pluronic ^® F 77, Pluronic ^® F 87, Pluronic ^® F 88, Pluronic ^® F 98, Pluronic ^® F 127, Pluronic ^® P 181 and Pluronic ^® P 407 is an aqueous dispersion of organic light-heat the nanoparticles is selected from the group consisting of. The aqueous dispersion photothermal organic nanoparticles of claim 1, wherein the diameter is 10 to 200 nm. The aqueous dispersion photothermal organic nanoparticles according to any one of claims 1 to 8, which is used for treatment of hyperthermia in vivo. 10. The aqueous dispersed light-heat nanoparticles of claim 9, wherein the hyperthermia treatment is performed on cancer tissue in vivo. (a) uniformly dissolving a hydrophobic photothermal organic material and a surfactant in an organic solvent, and then removing the organic solvent,
(b) dispersing the product of step (a) in water
A method of producing a water-based dispersed photothermal organic nanoparticles comprising a. The method of claim 11, wherein the aqueous dispersion photothermal organic nanoparticles comprise a core comprising a hydrophobic photothermal organic material, a surfactant surrounding the core, and water. The method according to claim 11 or 12, wherein the hydrophobic photothermal organic material has an absorption wavelength in the range of 600 to 900 nm. The method according to claim 13, wherein the hydrophobic photothermal organic material is selected from the group consisting of cyanine (indocyanine, thiasianin, oxacyanine) and phthalocyanine. 15. The method of claim 14, wherein the hydrophobic photothermal organic material is iodide 1,1 ', 3,3,3', 3'-hexamethylindotricarbocyanine and iodide 3,3'-diethylthiatricarbocyanine Method for Producing Aqueous Dispersed Photothermal Organic Nanoparticles Which Are Selected The method according to claim 11 or 12, wherein the surfactant is poloxamer. The method of claim 16 wherein the poloxamer is Pluronic ^® F 38, Pluronic ^® F 68, Pluronic ^® F 77, Pluronic ^® F 87, Pluronic ^® F 88, Pluronic ^® F 98, The method for producing a fluorene will nick ^® F 127, which is selected from the group consisting of fluorene as a nick ^® P 181 and Pluronic ^® P 407. The production method according to claim 11 or 12, wherein the diameter of the aqueous dispersion photothermal organic nanoparticles is 10 to 200 nm. The method according to claim 11, wherein the organic solvent in step (a) is evaporated and removed at room temperature. The method of claim 11, wherein the organic solvent is at least one selected from the group consisting of dichloromethane, tetrahydrofuran, chloroform, ethyl acetate, and methanol. The method according to claim 11, wherein the water in step (b) is used 2 to 200 times by weight of the photothermal organic nanoparticles. (a) uniformly mixing the hydrophobic photothermal organic material and the surfactant at a high temperature, followed by rapid cooling,
(b) dispersing the product of step (a) in water
A method of producing a water-based dispersed photothermal organic nanoparticles comprising a. The method of claim 22, wherein the aqueous dispersion photothermal organic nanoparticles comprise a core comprising a hydrophobic photothermal organic material, a surfactant surrounding the core, and water. The method according to claim 22 or 23, wherein the hydrophobic photothermal organic material has an absorption wavelength in the range of 600 to 900 nm. 25. The method of claim 24, wherein the hydrophobic photothermal organic material is selected from the group consisting of cyanine-based (indocyanine-based, thiasianin-based) and phthalocyanine-based. The method of claim 25, wherein the hydrophobic photothermal organic material is 2,9,16,23-tetra- tert -butyl- 29H, 31H -phthalocyanine. The method of claim 22 or 23, wherein the surfactant is poloxamer. The method of claim 27, wherein the poloxamer is Pluronic ^® F 38, Pluronic ^® F 68, Pluronic ^® F 77, Pluronic ^® F 87, Pluronic ^® F 88, Pluronic ^® F 98, The method for producing a fluorene will nick ^® F 127, which is selected from the group consisting of fluorene as a nick ^® P 181 and Pluronic ^® P 407. The production method according to claim 22 or 23, wherein the diameter of the aqueous dispersion photothermal organic nanoparticles is 10 to 200 nm. The method of claim 22, wherein the hydrophobic photothermal organic material and the surfactant in step (a) are uniformly dispersed at 150 ° C. 24. The method of claim 22, wherein the rapid cooling in step (a) is performed in ice. The method according to claim 22, wherein the water in step (b) is used 2 to 200 times by weight of the photothermal organic nanoparticles.

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