CN111529944A - Photodynamic therapy system and method for glioma - Google Patents

Photodynamic therapy system and method for glioma Download PDF

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CN111529944A
CN111529944A CN202010335103.9A CN202010335103A CN111529944A CN 111529944 A CN111529944 A CN 111529944A CN 202010335103 A CN202010335103 A CN 202010335103A CN 111529944 A CN111529944 A CN 111529944A
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nanoparticles
module
photodynamic therapy
photosensitive
nanoparticle
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李付勇
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N5/0613—Apparatus adapted for a specific treatment
    • A61N5/062—Photodynamic therapy, i.e. excitation of an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0071—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by measuring fluorescence emission
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H20/00—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance
    • G16H20/40—ICT specially adapted for therapies or health-improving plans, e.g. for handling prescriptions, for steering therapy or for monitoring patient compliance relating to mechanical, radiation or invasive therapies, e.g. surgery, laser therapy, dialysis or acupuncture
    • G—PHYSICS
    • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H30/00—ICT specially adapted for the handling or processing of medical images
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0626—Monitoring, verifying, controlling systems and methods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N5/00—Radiation therapy
    • A61N5/06—Radiation therapy using light
    • A61N2005/0664—Details

Abstract

The invention belongs to the technical field of medical instruments, and discloses a photodynamic therapy system and a method for glioma, which comprises a nanoparticle preparation module, a light-sensitive drug analysis module and a light-sensitive drug analysis module, wherein the nanoparticle preparation module is used for coating nanoparticles on photosensitive drugs or crosslinking the nanoparticles in the nanoparticles through chemical bonds; the nanoparticle injection module is used for carrying out intravenous injection on the prepared nanoparticles; the nanoparticle tracking module is used for tracking the activity of the nanoparticles in the patient body through a two-photon confocal microscope; the image display module is used for displaying the images of the nanoparticle aggregation positions tracked by the nanoparticle tracking module; and the photodynamic therapy module is used for irradiating the nanoparticles delivered by the target tissue area by emitting radiation light with specific wavelength in the photodynamic therapy device. The laser positioning device is simple in structure, can realize positioning of glioma, and reduces side effects on the skin of a patient because laser only irradiates the glioma positioning position.

Description

Photodynamic therapy system and method for glioma
Technical Field
The invention belongs to the technical field of medical instruments, and particularly relates to a photodynamic therapy system and a photodynamic therapy method for glioma.
Background
At present, malignant glioma is a common invasive brain tumor, the average survival time of the high-grade glioma patients does not exceed 12 months at present, although a plurality of comprehensive treatments such as postoperative radiotherapy and chemotherapy exist at present, surgical resection is still the key for improving the survival time, and the curative effect of the auxiliary treatment depends on the maximum resection degree of the tumor to a great extent. Since glioma grows infiltratively, its tumor tissue and surrounding brain tissue have no well-defined boundaries, and even experienced neurosurgeons cannot achieve full surgical resection, the key to surgical treatment of glioma is to remove the surrounding infiltrated tumor tissue to the maximum extent and to retain normal brain tissue.
Photodynamic therapy and localization has been considered as the most promising new method for cancer therapy since the 80 s.20 th century, and is now widely used for photodynamic therapy of brain tumors, but has many disadvantages, including poor selectivity of tumors and long-term skin photosensitization side effects.
Through the above analysis, the problems and defects of the prior art are as follows:
(1) the current photodynamic localization and treatment has poor selectivity on tumors;
(2) current photodynamic positioning and treatment can produce photosensitive side effects on the skin of the patient.
Disclosure of Invention
In view of the problems of the prior art, the present invention provides a photodynamic therapy system and method for glioma.
The invention is thus achieved, a photodynamic therapy system for glioma comprising:
the nanoparticle preparation module is connected with the central control module and is used for wrapping the nanoparticles for photosensitive drug analysis or crosslinking the nanoparticles in the nanoparticles through chemical bonds;
in order to improve the loading capacity of the nanoparticles on the photosensitive drugs, amphiphilic molecules are adopted to modify the surfaces of the nanoparticles, and chitosan or alginic acid or polyethylene glycol molecules with good biocompatibility are used to modify the surfaces of the hydrophilic nanoparticles;
then dispersing the modified nano particles into a photosensitive drug solution, and crosslinking the organic fluorescent dye on the surfaces of the nano particles through chemical bonds along with the volatilization of a solvent in the photosensitive drug;
the nanoparticle injection module is connected with the central control module and is used for carrying out intravenous injection on the prepared nanoparticles;
the nanoparticle tracking module is connected with the central control module and is used for tracking the movement of the nanoparticles in the patient body through a two-photon confocal microscope;
the blood flowing speed of a patient and the speed of the moving direction of the nano particles are obtained by utilizing a line scanning technology of a two-photon confocal microscope, photosensitive drugs in the nano particles can identify specific tumor cells, and meanwhile, the nano particles have small enough size, can seep out from high-permeability tumor blood vessels, enter tumor tissues and concentrate around the tumor, so that the passive marking of the tumor is realized; meanwhile, the nanoparticles can be absorbed by tumor cells in a full drinking manner, so that after blood is circulated for many times, the aggregation positions of the nanoparticles can be observed, and the distribution of the tumor cells can be determined;
the image display module is connected with the central control module and is used for displaying the images of the nanoparticle aggregation positions tracked by the nanoparticle tracking module;
the photodynamic therapy module is connected with the central control module, and is used for irradiating the nanoparticles conveyed by the target tissue region by radiating light with a specific wavelength emitted by the photodynamic therapy device, and the photothermal effect generated by photosensitive drugs in the nanoparticles can induce the heat loss and apoptosis of tumor cells;
the central control module is connected with the nanoparticle preparation module, the nanoparticle injection module, the nanoparticle tracking module, the image display module and the photodynamic therapy module, and the preparation of the nanoparticles is realized by setting different process parameters of different photosensitive drugs in the nanoparticle preparation module; the input quantity of the nano particles is set through different tumor types; the trend of the nano particles in the body of the patient is tracked by controlling the two-photon confocal microscope; and the trend and the aggregation of the nano particles are displayed through a display screen, the photodynamic therapy device is started to irradiate the aggregation position of the nano particles after the specified time is reached or the aggregation of the nano particles is completed, and the irradiation time is set according to the actual aggregation condition.
Further, the photodynamic therapy system for glioma further comprises:
the support module is connected with each module and used for realizing the fixed installation and support of each module;
and the power module is connected with each module and used for providing power support for the normal operation of each module.
Furthermore, the laser wavelength emitted by the photodynamic therapy device is 628nm, and the total energy is 260J/cm2。
Further, the nanoparticle preparation module includes:
the nano particle preparation unit is used for preparing nano particles by taking a mixture of oleate, sodium fluoride, oleic acid and octadecene as a raw material through a high-temperature pyrolysis method;
the nano-particle modification unit is used for modifying the surface of the nano-particles by adopting amphiphilic molecules and modifying the surface of the hydrophilic nano-particles by using chitosan or alginic acid or polyethylene glycol molecules with good biocompatibility;
and the drug wrapping unit is used for dispersing the modified nanoparticles into a photosensitive drug solution and crosslinking the organic fluorescent dye on the surfaces of the nanoparticles through chemical bonds.
Further, the specific steps of preparing the nanoparticles in the nanoparticle preparation unit are as follows:
heating a mixture of oleate, sodium fluoride, oleic acid and octadecene to 105-110 ℃, and introducing nitrogen for reaction for 0.5-1 h when no bubbles exist;
then heating to 300-305 ℃, introducing nitrogen, stirring, reacting for 1-1.5 h, and then naturally cooling to room temperature;
washing with ethanol, and dispersing in cyclohexane liquid; the oleate comprises gadolinium oleate, ytterbium oleate and thulium oleate;
adding distilled water into PEI, stirring uniformly at room temperature, then dropwise adding the nano particles obtained in the step (1) and stored in a cyclohexane solution for further 24 hours, subsequently evaporating at the temperature of 80 ℃ to remove cyclohexane, and centrifuging.
Further, the specific modification method adopted by the nanoparticle modification unit is as follows:
mixing PEG-PLGA amphiphilic polymer, hydrophobic drug and hydrophilic drug to obtain first emulsion;
mixing and emulsifying the first emulsion and an emulsifier to obtain a second emulsion, wherein the volume ratio of the first emulsion to the emulsifier is 1: 5-20;
separating the second emulsion to obtain loaded nanoparticles;
transferrin is used as a ligand of the nano-particles, PEG-PLGA amphiphilic polymer is used as a framework material, and an emulsifier volatilization method is adopted to carry out loading, so as to obtain the transferrin modified nano-particles carrying the double drugs.
Further, the preparation method of the photosensitive medicine comprises the following steps:
1) dispersing the black phosphorus nanosheets in N, N-dimethylformamide to obtain a black phosphorus nanosheet solution;
2) dissolving bismuth citrate in N, N-dimethylformamide to obtain a bismuth citrate solution;
3) adding the bismuth citrate solution obtained in the step 2) into the black phosphorus nanosheet solution obtained in the step 1), standing, centrifuging, and extracting the photosensitizer.
Another object of the present invention is to provide a method for photodynamic therapy of glioma, comprising the following steps:
setting different process parameters for a preparation device according to different photosensitive drugs, and preparing photosensitive nanoparticles;
setting the input quantity of photosensitive nanoparticles according to different tumor types, fully mixing the photosensitive nanoparticles with normal saline through a micro stirrer, and inputting the photosensitive nanoparticles into the veins of patients through an injector;
step three, tracking the trend of the nano particles in the patient body through a two-photon confocal microscope; and displaying the trend and aggregation of the nano particles through a display screen;
and step four, starting the photodynamic therapy device to irradiate the aggregation position of the nanoparticles after the specified time or the nanoparticles are aggregated, and setting the irradiation time according to the actual aggregation condition.
Further, the preparation method of the photosensitive nanoparticles comprises the following specific steps:
firstly, modifying the surface of a nanoparticle by using an amphiphilic molecule;
secondly, surface modification is carried out on the nano particles through chitosan, alginic acid or polyethylene glycol molecules;
and thirdly, dispersing the modified nanoparticles into a photosensitive drug solution, and crosslinking the photosensitive drug on the surfaces of the nanoparticles through chemical bonds along with the volatilization of a photosensitive drug solvent under the action of heating and other modes of the photosensitive drug solution by a preparation device.
Further, the method for tracking the movement of the nanoparticles in the patient by the two-photon confocal microscope specifically comprises the following steps:
(1) identifying the fluorescence generated by the photosensitive nanoparticles by a two-photon confocal microscope;
(2) obtaining the blood flow speed of a patient and the speed of the moving direction of the nano particles by utilizing a line scanning technology of a two-photon confocal microscope;
(3) and the gathering position of the photosensitive nano particles is subjected to image acquisition and amplification processing.
By combining all the technical schemes, the invention has the advantages and positive effects that:
the nanoparticle preparation module is used for wrapping the nanoparticles for photosensitive drug analysis or crosslinking the nanoparticles in the nanoparticles through chemical bonds; the nanoparticle injection module is used for carrying out intravenous injection on the prepared nanoparticles; the nanoparticle tracking module is used for tracking the activity of the nanoparticles in the patient body through a two-photon confocal microscope; the image display module is used for displaying the images of the nanoparticle aggregation positions tracked by the nanoparticle tracking module; and the photodynamic therapy module is used for irradiating the nanoparticles delivered by the target tissue area by emitting radiation light with specific wavelength in the photodynamic therapy device. The structure is simple, the glioma can be positioned, laser only irradiates the glioma positioning position, and side effects on the skin of a patient are reduced.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings needed to be used in the embodiments of the present application will be briefly described below, and it is obvious that the drawings described below are only some embodiments of the present application, and it is obvious for those skilled in the art that other drawings can be obtained from the drawings without creative efforts.
Fig. 1 is a schematic structural diagram of a photodynamic therapy system for glioma provided in an embodiment of the present invention.
In the figure: 1. a nanoparticle preparation module; 2. a nanoparticle injection module; 3. a nanoparticle tracking module; 4. an image display module; 5. a photodynamic therapy module; 6. a central control module; 7. a support module; 8. and a power module.
FIG. 2 is a block diagram of a nanoparticle preparation module according to an embodiment of the present invention.
Fig. 3 is a flowchart of a method for photodynamic therapy of glioma provided by an embodiment of the present invention.
Fig. 4 is a flow chart of a method for preparing photosensitive nanoparticles according to an embodiment of the present invention.
Fig. 5 is a flowchart of a method for tracking the movement of nanoparticles in a patient by a two-photon confocal microscope according to an embodiment of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
In view of the problems of the prior art, the present invention provides a system and a method for photodynamic therapy of glioma, which are described in detail below with reference to the accompanying drawings.
As shown in fig. 1, the present invention provides a photodynamic therapy system for glioma, comprising:
the nano particle preparation module 1 is connected with the central control module 6 and is used for wrapping the nano particles for photosensitive drug analysis or crosslinking the nano particles in the nano particles through chemical bonds;
in order to improve the loading capacity of the nanoparticles on the photosensitive drugs, amphiphilic molecules are adopted to modify the surfaces of the nanoparticles, and chitosan or alginic acid or polyethylene glycol molecules with good biocompatibility are used to modify the surfaces of the hydrophilic nanoparticles;
then dispersing the modified nano particles into a photosensitive drug solution, and crosslinking the organic fluorescent dye on the surfaces of the nano particles through chemical bonds along with the volatilization of a solvent in the photosensitive drug;
the nanoparticle injection module 2 is connected with the central control module 6 and is used for carrying out intravenous injection on the prepared nanoparticles;
the nanoparticle tracking module 3 is connected with the central control module 6 and used for tracking the activity of the nanoparticles in the patient body through a two-photon confocal microscope;
the blood flowing speed of a patient and the speed of the moving direction of the nano particles are obtained by utilizing a line scanning technology of a two-photon confocal microscope, photosensitive drugs in the nano particles can identify specific tumor cells, and meanwhile, the nano particles have small enough size, can seep out from high-permeability tumor blood vessels, enter tumor tissues and concentrate around the tumor, so that the passive marking of the tumor is realized; meanwhile, the nanoparticles can be absorbed by tumor cells in a full drinking manner, so that after blood is circulated for many times, the aggregation positions of the nanoparticles can be observed, and the distribution of the tumor cells can be determined;
the image display module 4 is connected with the central control module 6 and is used for displaying images of the nanoparticle aggregation positions tracked by the nanoparticle tracking module 3;
the photodynamic therapy module 5 is connected with the central control module 6, and performs illumination radiation on the nanoparticles conveyed by the target tissue region by emitting radiation light with specific wavelength in the photodynamic therapy device, and the photothermal effect generated by photosensitive drugs in the nanoparticles can induce the heat loss and apoptosis of tumor cells;
the central control module 6 is connected with the nanoparticle preparation module 1, the nanoparticle injection module 2, the nanoparticle tracking module 3, the image display module 4 and the photodynamic therapy module 5, and the preparation of the nanoparticles is realized by setting different process parameters of different photosensitive drugs in the nanoparticle preparation module 1; the input quantity of the nano particles is set through different tumor types; the trend of the nano particles in the body of the patient is tracked by controlling the two-photon confocal microscope; and the trend and the aggregation of the nano particles are displayed through a display screen, the photodynamic therapy device is started to irradiate the aggregation position of the nano particles after the specified time is reached or the aggregation of the nano particles is completed, and the irradiation time is set according to the actual aggregation condition.
As shown in fig. 1, the photodynamic therapy system for glioma provided by the embodiment of the present invention further includes:
the support module 7 is connected with each module and used for realizing the fixed installation and support of each module;
and the power module 8 is connected with each module and used for providing power support for the normal operation of each module.
The laser wavelength emitted by the photodynamic therapy device provided by the invention is 628nm, and the total energy is 260J/cm2。
As shown in fig. 2, the nanoparticle preparation module according to the embodiment of the present invention includes:
the nano particle preparation unit is used for preparing nano particles by taking a mixture of oleate, sodium fluoride, oleic acid and octadecene as a raw material through a high-temperature pyrolysis method;
the nano-particle modification unit is used for modifying the surface of the nano-particles by adopting amphiphilic molecules and modifying the surface of the hydrophilic nano-particles by using chitosan or alginic acid or polyethylene glycol molecules with good biocompatibility;
and the drug wrapping unit is used for dispersing the modified nanoparticles into a photosensitive drug solution and crosslinking the organic fluorescent dye on the surfaces of the nanoparticles through chemical bonds.
The specific steps for preparing the nanoparticles in the nanoparticle preparation unit provided by the embodiment of the invention are as follows:
heating a mixture of oleate, sodium fluoride, oleic acid and octadecene to 105-110 ℃, and introducing nitrogen for reaction for 0.5-1 h when no bubbles exist;
then heating to 300-305 ℃, introducing nitrogen, stirring, reacting for 1-1.5 h, and then naturally cooling to room temperature;
washing with ethanol, and dispersing in cyclohexane liquid; the oleate comprises gadolinium oleate, ytterbium oleate and thulium oleate;
adding distilled water into PEI, stirring uniformly at room temperature, then dropwise adding the nano particles obtained in the step (1) and stored in a cyclohexane solution for further 24 hours, subsequently evaporating at the temperature of 80 ℃ to remove cyclohexane, and centrifuging.
The specific modification method adopted by the nanoparticle modification unit provided by the embodiment of the invention is as follows:
mixing PEG-PLGA amphiphilic polymer, hydrophobic drug and hydrophilic drug to obtain first emulsion;
mixing and emulsifying the first emulsion and an emulsifier to obtain a second emulsion, wherein the volume ratio of the first emulsion to the emulsifier is 1: 5-20;
separating the second emulsion to obtain loaded nanoparticles;
transferrin is used as a ligand of the nano-particles, PEG-PLGA amphiphilic polymer is used as a framework material, and an emulsifier volatilization method is adopted to carry out loading, so as to obtain the transferrin modified nano-particles carrying the double drugs.
The preparation method of the photosensitive medicine provided by the embodiment of the invention comprises the following steps:
1) dispersing the black phosphorus nanosheets in N, N-dimethylformamide to obtain a black phosphorus nanosheet solution;
2) dissolving bismuth citrate in N, N-dimethylformamide to obtain a bismuth citrate solution;
3) adding the bismuth citrate solution obtained in the step 2) into the black phosphorus nanosheet solution obtained in the step 1), standing, centrifuging, and extracting the photosensitizer.
The working method of the photodynamic therapy system for glioma provided by the embodiment of the invention comprises the following specific steps:
s101: setting different technological parameters for the preparation device according to different photosensitive drugs, and preparing photosensitive nanoparticles;
s102: setting the input amount of the photosensitive nanoparticles according to different tumor types, fully mixing the photosensitive nanoparticles with normal saline through a micro stirrer, and inputting the photosensitive nanoparticles into the veins of patients through an injector;
s103: tracking the trend of the nano particles in the body of the patient through a two-photon confocal microscope; and displaying the trend and aggregation of the nano particles through a display screen;
s104: and starting the photodynamic therapy device to irradiate the aggregation position of the nanoparticles after the specified time is reached or the nanoparticles are aggregated to finish aggregation, and setting the irradiation time according to the actual aggregation condition.
The preparation method of the photosensitive nanoparticles provided by the invention comprises the following specific steps:
s201: firstly, modifying the surface of a nano particle by using amphiphilic molecules;
s202: and surface modification is carried out on the nano particles through chitosan, alginic acid or polyethylene glycol molecules;
s203: and then dispersing the modified nanoparticles into a photosensitive drug solution, and under the action of heating and other modes of the photosensitive drug solution by a preparation device, along with the volatilization of a photosensitive drug solvent, crosslinking the photosensitive drug on the surfaces of the nanoparticles through chemical bonds.
The invention provides a method for tracking the movement of nano particles in a patient by a two-photon confocal microscope, which comprises the following steps:
s301: identifying the fluorescence generated by the photosensitive nanoparticles by a two-photon confocal microscope;
s302: obtaining the blood flow speed of a patient and the speed of the moving direction of the nano particles by utilizing a line scanning technology of a two-photon confocal microscope;
s303: and the gathering position of the photosensitive nano particles is subjected to image acquisition and amplification processing.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention, and the scope of the present invention is not limited thereto, and any modification, equivalent replacement, and improvement made by those skilled in the art within the technical scope of the present invention disclosed herein, which is within the spirit and principle of the present invention, should be covered by the present invention.

Claims (10)

1. A photodynamic therapy system for glioma, characterized in that it comprises:
the nanoparticle preparation module is connected with the central control module and is used for wrapping the nanoparticles for photosensitive drug analysis or crosslinking the nanoparticles in the nanoparticles through chemical bonds;
in order to improve the loading capacity of the nanoparticles on the photosensitive drugs, amphiphilic molecules are adopted to modify the surfaces of the nanoparticles, and chitosan or alginic acid or polyethylene glycol molecules with good biocompatibility are used to modify the surfaces of the hydrophilic nanoparticles;
then dispersing the modified nano particles into a photosensitive drug solution, and crosslinking the organic fluorescent dye on the surfaces of the nano particles through chemical bonds along with the volatilization of a solvent in the photosensitive drug;
the nanoparticle injection module is connected with the central control module and is used for carrying out intravenous injection on the prepared nanoparticles;
the nanoparticle tracking module is connected with the central control module and is used for tracking the movement of the nanoparticles in the patient body through a two-photon confocal microscope;
the blood flowing speed of a patient and the speed of the moving direction of the nano particles are obtained by utilizing a line scanning technology of a two-photon confocal microscope, photosensitive drugs in the nano particles can identify specific tumor cells, and meanwhile, the nano particles have small enough size, can seep out from high-permeability tumor blood vessels, enter tumor tissues and concentrate around the tumor, so that the passive marking of the tumor is realized; meanwhile, the nanoparticles can be absorbed by tumor cells in a full drinking manner, so that after blood is circulated for many times, the aggregation positions of the nanoparticles can be observed, and the distribution of the tumor cells can be determined;
the image display module is connected with the central control module and is used for displaying the images of the nanoparticle aggregation positions tracked by the nanoparticle tracking module;
the photodynamic therapy module is connected with the central control module, and is used for irradiating the nanoparticles conveyed by the target tissue region by radiating light with a specific wavelength emitted by the photodynamic therapy device, and the photothermal effect generated by photosensitive drugs in the nanoparticles can induce the heat loss and apoptosis of tumor cells;
the central control module is connected with the nanoparticle preparation module, the nanoparticle injection module, the nanoparticle tracking module, the image display module and the photodynamic therapy module, and the preparation of the nanoparticles is realized by setting different process parameters of different photosensitive drugs in the nanoparticle preparation module; the input quantity of the nano particles is set through different tumor types; the trend of the nano particles in the body of the patient is tracked by controlling the two-photon confocal microscope; and the trend and the aggregation of the nano particles are displayed through a display screen, the photodynamic therapy device is started to irradiate the aggregation position of the nano particles after the specified time is reached or the aggregation of the nano particles is completed, and the irradiation time is set according to the actual aggregation condition.
2. The photodynamic therapy system for glioma of claim 1, wherein the photodynamic therapy system for glioma further comprises:
the support module is connected with each module and used for realizing the fixed installation and support of each module;
and the power module is connected with each module and used for providing power support for the normal operation of each module.
3. The photodynamic therapy system for glioma of claim 1, wherein the photodynamic therapy device emits a laser wavelength of 628nm and a total energy of 260J/cm2。
4. The photodynamic therapy system for glioma of claim 1, wherein the nanoparticle preparation module comprises:
the nano particle preparation unit is used for preparing nano particles by taking a mixture of oleate, sodium fluoride, oleic acid and octadecene as a raw material through a high-temperature pyrolysis method;
the nano-particle modification unit is used for modifying the surface of the nano-particles by adopting amphiphilic molecules and modifying the surface of the hydrophilic nano-particles by using chitosan or alginic acid or polyethylene glycol molecules with good biocompatibility;
and the drug wrapping unit is used for dispersing the modified nanoparticles into a photosensitive drug solution and crosslinking the organic fluorescent dye on the surfaces of the nanoparticles through chemical bonds.
5. The photodynamic therapy system for glioma of claim 4, wherein the nanoparticle preparation unit is configured to prepare nanoparticles by the specific steps of:
heating a mixture of oleate, sodium fluoride, oleic acid and octadecene to 105-110 ℃, and introducing nitrogen for reaction for 0.5-1 h when no bubbles exist;
then heating to 300-305 ℃, introducing nitrogen, stirring, reacting for 1-1.5 h, and then naturally cooling to room temperature;
washing with ethanol, and dispersing in cyclohexane liquid; the oleate comprises gadolinium oleate, ytterbium oleate and thulium oleate;
adding distilled water into PEI, stirring uniformly at room temperature, then dropwise adding the nano particles obtained in the step (1) and stored in a cyclohexane solution for further 24 hours, subsequently evaporating at the temperature of 80 ℃ to remove cyclohexane, and centrifuging.
6. The photodynamic therapy system for glioma of claim 4, wherein the nanoparticle modification unit is modified by a specific modification method:
mixing PEG-PLGA amphiphilic polymer, hydrophobic drug and hydrophilic drug to obtain first emulsion;
mixing and emulsifying the first emulsion and an emulsifier to obtain a second emulsion, wherein the volume ratio of the first emulsion to the emulsifier is 1: 5-20;
separating the second emulsion to obtain loaded nanoparticles;
transferrin is used as a ligand of the nano-particles, PEG-PLGA amphiphilic polymer is used as a framework material, and an emulsifier volatilization method is adopted to carry out loading, so as to obtain the transferrin modified nano-particles carrying the double drugs.
7. The photodynamic therapy system for glioma of claim 1 wherein the photosensitizing drug is prepared by a method comprising:
1) dispersing the black phosphorus nanosheets in N, N-dimethylformamide to obtain a black phosphorus nanosheet solution;
2) dissolving bismuth citrate in N, N-dimethylformamide to obtain a bismuth citrate solution;
3) adding the bismuth citrate solution obtained in the step 2) into the black phosphorus nanosheet solution obtained in the step 1), standing, centrifuging, and extracting the photosensitizer.
8. A photodynamic therapy method for glioma using the photodynamic therapy system for glioma according to any one of claims 1 to 7, characterized in that the photodynamic therapy method for glioma specifically comprises:
setting different process parameters for a preparation device according to different photosensitive drugs, and preparing photosensitive nanoparticles;
setting the input quantity of photosensitive nanoparticles according to different tumor types, fully mixing the photosensitive nanoparticles with normal saline through a micro stirrer, and inputting the photosensitive nanoparticles into the veins of patients through an injector;
step three, tracking the trend of the nano particles in the patient body through a two-photon confocal microscope; and displaying the trend and aggregation of the nano particles through a display screen;
and step four, starting the photodynamic therapy device to irradiate the aggregation position of the nanoparticles after the specified time or the nanoparticles are aggregated, and setting the irradiation time according to the actual aggregation condition.
9. The method of claim 8, wherein the photosensitive nanoparticles are prepared by the following steps:
firstly, modifying the surface of a nanoparticle by using an amphiphilic molecule;
secondly, surface modification is carried out on the nano particles through chitosan, alginic acid or polyethylene glycol molecules;
and thirdly, dispersing the modified nanoparticles into a photosensitive drug solution, and crosslinking the photosensitive drug on the surfaces of the nanoparticles through chemical bonds along with the volatilization of a photosensitive drug solvent under the action of heating and other modes of the photosensitive drug solution by a preparation device.
10. The method of claim 8, wherein the two-photon confocal microscope is used for tracking the movement of the nanoparticles in the patient, and the method comprises:
(1) identifying the fluorescence generated by the photosensitive nanoparticles by a two-photon confocal microscope;
(2) obtaining the blood flow speed of a patient and the speed of the moving direction of the nano particles by utilizing a line scanning technology of a two-photon confocal microscope;
(3) and the gathering position of the photosensitive nano particles is subjected to image acquisition and amplification processing.
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US20020127224A1 (en) * 2001-03-02 2002-09-12 James Chen Use of photoluminescent nanoparticles for photodynamic therapy
CN202078655U (en) * 2010-03-25 2011-12-21 阿卜杜拉·库尔卡耶夫 Photodynamic therapy equipment for living organism tissues
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