CN107137709A - A kind of photodynamic therapy system and the method for persistently producing singlet oxygen - Google Patents
A kind of photodynamic therapy system and the method for persistently producing singlet oxygen Download PDFInfo
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- CN107137709A CN107137709A CN201710373050.8A CN201710373050A CN107137709A CN 107137709 A CN107137709 A CN 107137709A CN 201710373050 A CN201710373050 A CN 201710373050A CN 107137709 A CN107137709 A CN 107137709A
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- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 title claims abstract description 33
- 238000002428 photodynamic therapy Methods 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 title claims abstract description 20
- 239000002105 nanoparticle Substances 0.000 claims abstract description 141
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 79
- 229910052747 lanthanoid Inorganic materials 0.000 claims abstract description 74
- 150000002602 lanthanoids Chemical class 0.000 claims abstract description 74
- 239000001301 oxygen Substances 0.000 claims abstract description 74
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 74
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- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 1
- 229940078795 lactoferrin Drugs 0.000 description 1
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- 229910052727 yttrium Inorganic materials 0.000 description 1
- VWQVUPCCIRVNHF-UHFFFAOYSA-N yttrium atom Chemical compound [Y] VWQVUPCCIRVNHF-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61G—TRANSPORT, PERSONAL CONVEYANCES, OR ACCOMMODATION SPECIALLY ADAPTED FOR PATIENTS OR DISABLED PERSONS; OPERATING TABLES OR CHAIRS; CHAIRS FOR DENTISTRY; FUNERAL DEVICES
- A61G10/00—Treatment rooms or enclosures for medical purposes
- A61G10/02—Treatment rooms or enclosures for medical purposes with artificial climate; with means to maintain a desired pressure, e.g. for germ-free rooms
- A61G10/023—Rooms for the treatment of patients at over- or under-pressure or at a variable pressure
- A61G10/026—Rooms for the treatment of patients at over- or under-pressure or at a variable pressure for hyperbaric oxygen therapy
-
- 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
- A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/143—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with inorganic compounds
-
- 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
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/067—Radiation therapy using light using laser light
-
- 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
- A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
- A61N2005/0659—Radiation therapy using light characterised by the wavelength of light used infrared
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pathology (AREA)
- Radiology & Medical Imaging (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Emergency Medicine (AREA)
- Physics & Mathematics (AREA)
- Inorganic Chemistry (AREA)
- Optics & Photonics (AREA)
- Pulmonology (AREA)
- Biophysics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A kind of method for the present invention relates to photodynamic therapy system and persistently producing singlet oxygen.The invention discloses a kind of multi-functional group of the lanthanides nano particle, its preparation method, and a kind of method and photodynamic therapy system that singlet oxygen is produced using the nano particle, by combining hyperbaric oxygen chamber, the group of the lanthanides nano particle is excited in near-infrared laser, realize oxygen supply enhanced sensitivity, so as to promote the targeting conveying and the generation of singlet oxygen of nanoparticulate drug, thus solve prior art singlet oxygen and produce the not good technical problem of not enough, photodynamic therapy system effect.
Description
Technical field
The invention belongs to field of medical device, more particularly, to a kind of photodynamic therapy system.
Background technology
Optical dynamic therapy is a kind of noninvasive laser therapy means, is widely used to the treatment of clinical superficial type tumour, its
Have the advantages that selective high, toxic side effect is small, wound is small.But the wavelength of sensitiser absorption is generally ultraviolet or visible at present
Light, the tissue penetration depths of the band of light are shallower；Secondly, sensitising agent is generated dependent on oxygen and lacked inside oxygen radical, tumor tissues
The microenvironment of oxygen causes its low yield.Therefore, light penetration depth, alleviation tumor locus anoxic and then raising in the tissue are improved
The problem of single line oxygen yield is the problem that clinical optical dynamic therapy need to overcome.
The penetration depth of light in biological tissues depends on multiple parameters, includes wavelength, intensity, coherence and the tissue of light
Physiologic character etc..Cytotoxicity is caused in order to produce enough single line oxygen, the spectrum that light source is sent should be with sensitising agent most
Big absorbing wavelength scope is consistent.The conventional irradiation light of clinic is ultraviolet, visible ray, and the luminous energy of this wave band is by blood in biological tissue
Lactoferrin, melanin etc. effectively absorb, and causing the light of this wave band can not be penetrated into inside tumor tissues.Wavelength 700~
1300nm luminous energy is prevented effectively from other and excites interference and damage with launch wavelength to tissue, deep with good tissue penetration
Degree, is referred to as " optical window " or " infrared window ".Absorbed because the sensitising agent clinically used exists near infrared region
Extremely weak the problems such as, so far near infrared light seldom directly apply to optical dynamic therapy.The development of conversion nano particle in group of the lanthanides,
To realize that application of the near infrared light in optical dynamic therapy provides possibility.With stable luminescence, it is difficult photobleaching, high s/n ratio
The advantages of, have evolved into the emerging nano material of the class of biomedical sector one.Conversion nano particle is by absorbing two in group of the lanthanides
Individual or multiple near-infrared photons are converted to the photon of a high energy, produce ultraviolet, visible or near-infrared transmitting light.Therefore, it is sharp
Traditional UV, the sensitising agent of visible absorption are excited with conversion nano particle Upconversion luminescence in group of the lanthanides, group of the lanthanides is built
Upper conversion nano particle optical dynamic therapy system, is that the sensitising agent for solving Clinical practice absorbs extremely weak problem near infrared region
Effective means.Conversion nano particle uses 980nm laser excitations in traditional group of the lanthanides.But the water in biological tissue is to 980nm light
Absorb very big, potential fire damage can be caused.Comparatively, biological tissue it is weaker to 808nm light absorbs, to tissue fire damage
It is small, it is important that 808nm light sources can also provide higher tissue penetration depths, changed so building in the group of the lanthanides that 808nm is excited
Nano particle is international research focus in recent years.Conversion nano particle in the group of the lanthanides that effective 808nm is excited is built, usually using neodymium
As main sensitizer, still, neodymium has the features such as multiple energy level, energy jump are complicated, quenching effect is strong, significantly reduces neodymium
Conversion nano particle fluorescence efficiency in group of the lanthanides.Conversion nano particle light power in the neodymium group of the lanthanides that efficient 808nm is excited is built to control
Treatment system, it is to realize 808nm light sources one of urgent problem to be solved in optical dynamic therapy application to improve singlet oxygen yield.
Most of entity tumor growths are quick, with the propagation of tumour cell, and its distance with interstitial blood vessel around is continuous
Increase, causes inside tumor severe depletion of oxygen.Further, since tumor neogenetic blood vessels fast growth, structure distribution are disorderly, tube chamber is easy
In the reason such as collapsing, inside tumor can further anoxic.The tumor microenvironment of anoxic in turn further dislike again by meeting inducing tumor
Change, while reducing various treatment methods (such as chemotherapy, radiation) to the therapeutic effect of tumour.Needed during optical dynamic therapy
Continuous consumption oxygen, can accelerate tumor hypoxia.Therefore, how tumor hypoxia is solved, is that optical dynamic therapy treatment is urgently to be resolved hurrily
One of problem.Study at present and used the oxygen supply " from method for supplying oxygen " more, for example：" oxygen supply of perfluocarbon oxygen carrying ", nano-silica
Change the oxygen supply of manganese catalyzing hydrogen peroxide, erythrocyte membrane pack, utilize catalase catalyzing hydrogen peroxide oxygen supply etc..But, this
A little methods still suffer from the problems such as efficiency of oxygen supply is low, stability is poor, Clinical feasibility is not enough.
The content of the invention
For the disadvantages described above or Improvement requirement of prior art, the invention provides a kind of multi-functional group of the lanthanides nano particle,
Its preparation method, and a kind of method and photodynamic therapy system that singlet oxygen is produced using the nano particle, its purpose are existed
In by building the group of the lanthanides nano particle, while exciting the group of the lanthanides nano particle using near-infrared laser, and combine hyperbaric oxygen
Cabin, realizes oxygen supply oxygenation, so as to promote the targeting conveying and the generation of singlet oxygen of nanoparticulate drug, thus solves existing
Technology singlet oxygen produces the not good technical problem of not enough, photodynamic therapy system effect.
To achieve the above object, according to one aspect of the present invention there is provided a kind of group of the lanthanides nano particle, the group of the lanthanides is received
Rice grain kernel has the sandwich structure wrapped up layer by layer, and shell is mesoporous silicon layer, and the chemical composition of the sandwich structure is
NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,Caz@mSiO2, wherein 0≤x≤0.3；0≤y
≤0.05；0≤z≤0.1；0≤t≤0.4, the thickness of the mesoporous silicon layer is 2~20nm.
Preferably, the average grain diameter of the group of the lanthanides nano particle kernel is 10~100nm.
Preferably, the nano grain surface is adsorbed with sensitising agent, and the sensitising agent is at 520nm, 550nm or 660nm
There is the sensitising agent of absorption.
Preferably, the sensitising agent is rose-red, MC540, methyl blue or chlorin.
According to another aspect of the present invention there is provided a kind of preparation method of described group of the lanthanides nano particle, including such as
Lower step：
1) oleic acid and octadecylene are added into the mixture of gadolinium, yttrium acetate, acetic acid erbium and calcium acetate, in inert gas
130~160 DEG C are warming up under environment, 45~60min is stirred, obtains solution A；
2) solution A is cooled to 20~30 DEG C, the methanol that sodium hydroxide/ammonium fluoride is added dropwise into the solution A is molten
Liquid, obtains solution B；
3) solution B is warming up to 50~70 DEG C, vacuumizes removing methanol, in an inert atmosphere with 5~20 DEG C/
Min is warming up to 260~320 DEG C, reacts 30~50min, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,CazNano particle is mixed
Close liquid；
4) by the oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,CazNano particle mixed liquor is cooled to 20~30 DEG C, then
The ethanol of 2~4 times of mixeding liquid volumes is added, centrifugation obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,CazNano particle, uses second
Alcohol is washed, and is then dispersed in hexane, is obtained oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,CazThe hexane solution of nano particle；
5) oleic acid and octadecylene are added into the mixture of yttrium acetate and calcium acetate, is warming up in an inert atmosphere
130~160 DEG C, 45~60min is stirred, solution C is obtained；
6) solution C is cooled to 20~30 DEG C, the methanol that sodium hydroxide/ammonium fluoride is added dropwise into the solution C is molten
Liquid and the NaGd(1-x-y-z)F4:Ybx, Ery,CazThe hexane solution of nano particle, obtains solution D；
7) solution D is warming up to 50~70 DEG C, removing methanol and hexane is vacuumized, in an inert atmosphere with 5
~20 DEG C/min is warming up to 260~320 DEG C, reacts 30~50min, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@
NaYbF4:CazNano particle mixed liquor；
8) by the oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:CazNano particle mixed liquor is cooled to 20
~30 DEG C, the ethanol of 2~4 times of mixeding liquid volumes is added, centrifugation obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@
NaYbF4:CazNano particle, is washed with ethanol, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:CazNanometer
Finished granule；It is then dispersed in hexane, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:CazNano particle
Hexane solution；
9) oleic acid and octadecylene are added into the mixture of neodymium acetate, gadolinium and calcium acetate, in an inert atmosphere
130~160 DEG C are warming up to, 45~60min is stirred, obtains solution E；
10) solution E is cooled to 20~30 DEG C, the methanol that sodium hydroxide/ammonium fluoride is added dropwise into the solution C is molten
Liquid and the NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:CazThe hexane solution of nano particle, obtains solution F；
11) the solution F is warming up to 50~70 DEG C, removing methanol and hexane is vacuumized, in an inert atmosphere with 5
~20 DEG C/min is warming up to 260~320 DEG C, reacts 30~50min, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@
NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,CazNano particle mixed liquor；
12) by the oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,CazReceive
Rice grain mixed liquor is cooled to 20~30 DEG C, adds the ethanol of 2~4 times of mixeding liquid volumes, and centrifugation obtains oil-soluble
NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,CazNano particle, is washed with ethanol, is obtained
Oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,CazNano particle finished product, uses ethanol
Washing, is then dispersed in hexane, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:
Gdt,CazThe hexane solution of nano particle；
13) take cetyl trimethylammonium bromide to be added to the water, stir 0.5~2 hour, form solution G；Then heating
To 60~80 DEG C；
14) by the NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,CazNano particle
Hexane solution be added dropwise under the solution G, stirring condition react 0.5~48 hour；Then ethyl acetate, sodium hydroxide is added dropwise
With 50~300ul TEOS, react 2~8 hours under stirring condition, obtain Solution H；After the Solution H is centrifuged, obtain such as power
Profit requires the group of the lanthanides nano particle described in 1.
Preferably, 1mmol lanthanide compound, the oleic acid are often dissolved in step (1), step (5) and step (9)
Consumption is 3~10ml, and the octadecylene consumption is in 5~10ml；
According to another aspect of the present invention there is provided a kind of application of described group of the lanthanides nano particle, applied to preparation
Treat the medicine of tumour.
According to another aspect of the present invention, there is provided the side that a kind of utilization group of the lanthanides nano particle persistently produces singlet oxygen
Method, described group of the lanthanides nano particle is placed in high pressure oxygen environment, while carrying out near-infrared laser to the group of the lanthanides nano particle
Irradiation.
Preferably, the high pressure oxygen environment is provided by hyperbaric oxygen chamber.
Preferably, the wavelength of the near-infrared laser is 980,915,808 or 780nm.
Preferably, the time being placed in high pressure oxygen environment is 30min~4h/ times, and the pressure of the hyperbaric oxygen is big
In 1 atmospheric pressure, but no more than 3 atmospheric pressure.
According to another aspect of the present invention, there is provided a kind of photodynamic therapy system, the photodynamic therapy system bag
Include following module：Carry medicine module, hyperbaric oxygen supplying module and lighting module；
Wherein, the load medicine module is used for carrying medicament；The medicine is preferably that the group of the lanthanides of described load sensitising agent is received
Rice grain；
The hyperbaric oxygen supplying module is used to provide high pressure oxygen to the load medicine module, and the load medicine module is placed in described
In the high pressure oxygen environment that hyperbaric oxygen supplying module is provided；
The lighting module is used to provide illumination to the load medicine module, the medicine is persistently produced single line under light illumination
State oxygen.
The present invention builds a kind of group of the lanthanides nano particle that can be used for photodynamic therapy system, the structure of nano particle first
It is divided into three steps：It is to build a kind of group of the lanthanides nano particle of the sandwich structure wrapped up layer by layer first；Secondly, in sandwich structure
Group of the lanthanides nano grain surface forms mesoporous silicon layer, and the mesh of nano particle dispersiveness and load sensitising agent in water is improved to reach
's；3rd, by way of physical absorption, sensitising agent is connected on nano particle.The nano particle is in near-infrared laser
980th, 915,808, under 780nm exciting, with intracellular oxygen reaction, singlet oxygen is produced.Because tumour has the spy of weary oxygen
Levy, photodynamic therapy system needs the participation of oxygen to produce singlet oxygen, so how to improve the content of intracellular oxygen also
It is most important.The present invention is adsorbed with the group of the lanthanides nano particle of sensitising agent by using above-mentioned, and combines hyperbaric oxygen chamber, it is proposed that one
The method for persistently producing singlet oxygen is planted, the therapeutic effect of photodynamic therapy system is enhanced, while also improving nano particle
Conveyed in the targeting of tumour, enhance infiltration retention effect (the Enhanced Permeation and of nano-particle
Retention, EPR), both collaborations are realized, preferable therapeutic effect is reached.
In general, by the contemplated above technical scheme of the present invention compared with prior art, it can obtain down and show
Beneficial effect.
(1) the multi-functional group of the lanthanides nano particle prepared by the present invention is the composite nanometer particle of doping yttrium, erbium, neodymium etc., can
To be excited under near infrared light 980,915,808 or 780nm laser, green and red fluorescence are produced, up-conversion fluorescence is realized,
And fluorescence intensity is high；The multi-functional group of the lanthanides nano particle of oil-soluble excites fluorescence relative intensity after 60min to be still 98%, fluorescent stabilization
Property is good, can use for a long time；The multi-functional group of the lanthanides nano particle of oil-soluble of the present invention is excited again after several days, and fluorescence is relative
Intensity keeps stable, the phenomenon of no photobleaching.
(2) the oil-soluble multi-functional group of the lanthanides nano particle doping erbium prepared by the present invention, most hyperfluorescence launch wavelength is
550nm, fluorescence penetrability is good.
(3) the multi-functional group of the lanthanides nano particle of oil-soluble prepared by the present invention, size is 10~100nm, and granularity is small and equal
It is even.Preparation method is simple and easy to apply, be easy to control, can accuracy controlling oil-soluble group of the lanthanides by controlling reaction temperature and reaction time
Nano particle；Simultaneously short the time required to the preparation method, production efficiency is high.
(4) mesoporous silicon of the outer layer used in the present invention, size is effective to improve center luminous nano granule in 2~20nm
Water in dispersiveness, while providing carrier for the sensitising agent of load.
(5) sensitising agent used in the present invention can use rose-red or MC540, chlorin etc. 520,550 or
660nm wave bands have the sensitising agent of absorption.
(6) a kind of method for persistently producing singlet oxygen that the present invention is provided, the group of the lanthanides nanometer provided using the present invention
Burl closes near-infrared laser irradiation, due to being placed in high pressure oxygen environment, can constantly produce singlet oxygen.
(7) photodynamic therapy system that the present invention is provided, by using the multi-functional group of the lanthanides nano particle of specific oil-soluble,
And combine hyperbaric oxygen chamber, the meltage of tumor focus position oxygen is improved, lower constant generation is excited in near-infrared laser
Singlet oxygen, conveys in the targeting of tumour while high pressure oxygen environment can also improve nano particle, enhances the EPR of nano particle
Effect, realizes cooperative effect, therefore the photodynamic therapy system of the present invention can achieve good therapeutic effect.
Brief description of the drawings
Fig. 1 is the NaGd of kernel prepared by the embodiment of the present invention 10.68F4:Yb0.2, Er0.02,Ca0.1@NaYb0.9F4:Ca0.1@
NaNd0.6F4:Gd0.3,Ca0.1Transmission electron microscope picture (yardstick：50nm)；
Fig. 2 is water miscible NaGd0.68F4:Yb0.2, Er0.02,Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3,
Ca0.1@mSiO2Transmission electron microscope picture；
Fig. 3 a are NaGd0.68F4:Yb0.2, Er0.02,Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3,Ca0.1@
mSiO2Y value is intensity relative value in x-ray diffraction pattern, Fig. 3 a；Fig. 3 b are the oil solubility nanometer particle green emitting
Efficiency；
NaGd prepared by Fig. 4 embodiment of the present invention 10.68F4:Yb0.2, Er0.02,Ca0.1@NaYb0.9F4:Ca0.1@
NaNd0.6F4:Gd0.3,Ca0.1@mSiO2Ordinate in the singlet oxygen that-rose-red nano particle is produced under 808nm laser, Fig. 4
For DPBF (indicator that singlet oxygen is produced) fluorescence intensity relative value；
Fig. 5 is to compare figure in the targeting conveying effect of the tumour of mouse using the nano particle of the present invention；
Fig. 6 be using the present invention photodynamic therapy system and singlet oxygen production method to mouse tumor at
The result of reason.
Embodiment
In order to make the purpose , technical scheme and advantage of the present invention be clearer, it is right below in conjunction with drawings and Examples
The present invention is further elaborated.It should be appreciated that specific embodiment described herein is only to explain the present invention, not
For limiting the present invention.As long as in addition, technical characteristic involved in each embodiment of invention described below that
Not constituting conflict between this can just be mutually combined.
The group of the lanthanides nano particle that the present invention is provided, its kernel has the sandwich structure wrapped up layer by layer, and shell is mesoporous silicon
Layer, the wherein nano particle of kernel sandwich structure are oleic acid coordination bonding in nano particle plane of crystal, its structural chemistry group
As NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,Caz, wherein 0≤x≤0.3；0≤y≤
0.05；0≤z≤0.1；0≤t≤0.4, the shell of the sandwich structure is the mesoporous silicon layer of controllable thickness, wherein kernel three
The average grain diameter of the group of the lanthanides nano particle of Mingzhi's structure is 10~100nm, and the thickness of the mesoporous silicon layer of shell is 2~20nm.
There are preferred three kinds prepared by the present invention group of the lanthanides nanoparticle structure chemical compositions of core shell structure to be：
NaGd0.68F4:Yb0.2, Er0.02,Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3,Ca0.1@mSiO2Or
NaGd0.73F4:Yb0.2, Er0.02,Ca0.05@NaYb0.95F4:Ca0.05@NaNd0.65F4:Gd0.3,Ca0.05@mSiO2Or
NaGd0.7F4:Yb0.2, Er0.05,Ca0.05@NaYb0.95F4:Ca0.05@NaNd0.65F4:Gd0.3,Ca0.05@mSiO2。
Therefore, the overall average grain diameter of group of the lanthanides nano particle of the invention is 12~120nm.
The above-mentioned adsorbable sensitising agent of group of the lanthanides nano grain surface, the sensitising agent is to have absorption at 520,550,660nm
Sensitising agent, preferably rose-red, MC540, methyl blue or chlorin etc..
The preparation method of above-mentioned group of the lanthanides nano particle, comprises the following steps：
1) oleic acid and octadecylene are added into the mixture of gadolinium, yttrium acetate, acetic acid erbium and calcium acetate, in inert gas
130~160 DEG C are warming up under environment, 45~60min is stirred, obtains solution A；
2) solution A is cooled to 20~30 DEG C, the methanol that sodium hydroxide/ammonium fluoride is added dropwise into the solution A is molten
Liquid, obtains solution B；
3) solution B is warming up to 50~70 DEG C, vacuumizes removing methanol, in an inert atmosphere with 5~20 DEG C/
Min is warming up to 260~320 DEG C, reacts 30~50min, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,CazNano particle is mixed
Close liquid；
4) by the oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,CazNano particle mixed liquor is cooled to 20~30 DEG C, then
The ethanol of 2~4 times of mixeding liquid volumes is added, centrifugation obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,CazNano particle, uses second
Alcohol is washed, and is then dispersed in hexane, is obtained oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,CazThe hexane solution of nano particle；
5) oleic acid and octadecylene are added into the mixture of yttrium acetate and calcium acetate, is warming up in an inert atmosphere
130~160 DEG C, 45~60min is stirred, solution C is obtained；
6) solution C is cooled to 20~30 DEG C, the methanol that sodium hydroxide/ammonium fluoride is added dropwise into the solution C is molten
Liquid and the NaGd(1-x-y-z)F4:Ybx, Ery,CazThe hexane solution of nano particle, obtains solution D；
7) solution D is warming up to 50~70 DEG C, removing methanol and hexane is vacuumized, in an inert atmosphere with 5
~20 DEG C/min is warming up to 260~320 DEG C, reacts 30~50min, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@
NaYbF4:CazNano particle mixed liquor；
8) by the oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:CazNano particle mixed liquor is cooled to 20
~30 DEG C, the ethanol of 2~4 times of mixeding liquid volumes is added, centrifugation obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@
NaYbF4:CazNano particle, is washed with ethanol, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:CazNanometer
Finished granule；It is then dispersed in hexane, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:CazNano particle
Hexane solution；
9) oleic acid and octadecylene are added into the mixture of neodymium acetate, gadolinium and calcium acetate, in an inert atmosphere
130~160 DEG C are warming up to, 45~60min is stirred, obtains solution E；
10) solution E is cooled to 20~30 DEG C, the methanol that sodium hydroxide/ammonium fluoride is added dropwise into the solution C is molten
Liquid and the NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:CazThe hexane solution of nano particle, obtains solution F；
11) the solution F is warming up to 50~70 DEG C, removing methanol and hexane is vacuumized, in an inert atmosphere with 5
~20 DEG C/min is warming up to 260~320 DEG C, reacts 30~50min, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@
NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,CazNano particle mixed liquor；
12) by the oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,CazReceive
Rice grain mixed liquor is cooled to 20~30 DEG C, adds the ethanol of 2~4 times of mixeding liquid volumes, and centrifugation obtains oil-soluble
NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,CazNano particle, is washed with ethanol, is obtained
Oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,CazNano particle finished product, uses ethanol
Washing, is then dispersed in hexane, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:
Gdt,CazThe hexane solution of nano particle；
13) take cetyl trimethylammonium bromide to be added to the water, stir 0.5~2 hour, form solution G；Then heating
To 60~80 DEG C；
14) by the NaGd(1-x-y-z)F4:Ybx, Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,CazNano particle
Hexane solution be added dropwise under the solution G, stirring condition react 0.5~48 hour；Then ethyl acetate, sodium hydroxide is added dropwise
With 50~300ul TEOS, react 2~8 hours under stirring condition, obtain Solution H；After the Solution H is centrifuged, obtain such as power
Profit requires the group of the lanthanides nano particle described in 1.
Wherein, step 1), step 5) and step 9) in often dissolve 1mmol lanthanide compound, the oleic acid consumption
For 3~10ml, the octadecylene consumption is in 5~10ml.
Step 2) NH4F consumption is 3~4 times of lanthanide compound mole；Step 2) NaOH use
Measure as 2~3 times of lanthanide compound mole；Step 2) NaOH/NH is added dropwise4The time for adding of F methanol solution
For 1~10min.Step 6) and step 10) NH4F consumption is 1~2 times of lanthanide compound mole；Step 6)
With step 10) consumption of the NaOH is 1~1.5 times of lanthanide compound mole.
Step 13) the CTAB additions are 0.1g/10 milliliters of water.
Step 14) time for adding be 10 minutes~5 hours.
Load sensitising agent method be：Above-mentioned group of the lanthanides nano particle is distributed in appropriate water, in right amount photosensitive is added
The agent aqueous solution, is centrifuged, being loaded (absorption) has the group of the lanthanides nano particle of sensitising agent after stirring.
Group of the lanthanides nano particle of the present invention is a kind of multi-functional group of the lanthanides nano particle, can apply to prepare and treats swollen
The medicine of knurl.
Present invention also offers a kind of method that utilization group of the lanthanides nano particle persistently produces singlet oxygen, by that will be adsorbed with
The group of the lanthanides nano particle of sensitising agent is placed in high pressure oxygen environment, while carrying out near-infrared laser irradiation to the group of the lanthanides nano particle.
The concentration of group of the lanthanides nano particle is 10mg/ml, and consumption is 10~200ul, and the sensitising agent of group of the lanthanides nano grain surface is rose-red
When, the concentration of rose-red is 0.5~1g/10ml water, and the high pressure oxygen environment is provided by hyperbaric oxygen chamber, and the wavelength of near-infrared laser is
980th, 915,808 or 780nm.
When this method is used for into the treatment of tumour, the group of the lanthanides nano particle containing adsorption sensitising agent is placed in high pressure
Time in oxygen environment is 30min~4h/ time, and the pressure of hyperbaric oxygen is more than 1 atmospheric pressure, but no more than 3 atmospheric pressure, closely
The time of infrared laser irradiation is 5min~5h/ time, and the laser intensity is 0.35W/cm2~5W/cm2, can be according to singlet
Determine to be placed in number of times and the time of high pressure oxygen environment and illumination the need for oxygen yield.
The photodynamic therapy system of the present invention, including carry medicine module, hyperbaric oxygen supplying module and lighting module；Wherein, carry
Medicine module is used for the group of the lanthanides nano particle that carrier surface is adsorbed with sensitising agent；Hyperbaric oxygen supplying module is used to provide to load medicine module
High pressure oxygen, carries medicine module and is placed in the high pressure oxygen environment of hyperbaric oxygen supplying module offer；Lighting module is used for load medicine module
Illumination is provided, the group of the lanthanides nano particle of load sensitising agent is persistently produced singlet oxygen under light illumination, the singlet oxygen of generation is used
In the optical dynamic therapy of focus.
The present invention adjusts the fluorescent emission intensity of oil solubility nanometer particle by changing the species and proportioning of lanthanide series, such as
Use neodymium acetate, gadolinium, acetic acid erbium and calcium acetate for reacting precursor in embodiment, prepare oil-soluble NaGd0.68F4:
Yb0.2, Er0.02,Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3,Ca0.1Nano particle is small, uniform particle diameter with particle diameter
Feature.The nano particle is in the case where near infrared light 980,915,808 and 780nm are excited, and generation launch wavelength is 520,550 and
660nm fluorescence, fluorescence intensity is high, fluorescent stability is good；It is prepared when the doping level of erbium is 2% when erbium is the centre of luminescence
Oil solubility nanometer particle green emitting efficiency highest.The particle diameter of the oil solubility nanometer particle of the present invention passes through controlling reaction temperature
And time-controllable, temperature is higher, the reaction time is longer, and the particle diameter of oil solubility nanometer particle is bigger.
One layer of mesoporous silicon of outer layer covers of the nano particle of structure, on the one hand can improve the water solubility of nano particle, separately
On the one hand due to its controllable thickness, sensitising agent can be loaded as carrier.The load efficiency of sensitising agent and porosity, compare table
Area is relevant.
Above-mentioned nano particle under near infrared light 980nm, 915nm, 808nm and 780nm exciting, the 520nm of generation and
550nm fluorescence can be absorbed by the photosensitizer rose bengal of shell, in the cell under the participation of oxygen, produce singlet oxygen.
Because tumour has the feature of weary oxygen, and optical dynamic therapy can consume oxygen, therefore the light of prior art in itself
Dynamic therapy systemic therapeutic effects are low.The photodynamic therapy system that the present invention is provided, by way of combining hyperbaric oxygen chamber, reaches
To the purpose for the meltage for improving tumour oxygen, the effect of optical dynamic therapy is enhanced, is existed while also improving nano particle
The targeting conveying of tumor focus, enhances the infiltration retention effect (EPR effects) of nano particle, realizes both collaborations, reach
To preferable therapeutic effect.
It is embodiment below：
Embodiment 1
Prepare NaGd0.7F4:Yb0.18, Er0.02,Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3, Ca0.1@mSiO2-
Rose Bengal
1.1 prepare NaGd0.7F4:Yb0.18, Er0.02, Ca0.1
1) 0.7mmol gadoliniums, 0.18mmol yttrium acetates, 0.02mmol acetic acid erbiums, 0.1mmol calcium acetates, Xiang Qi are weighed
Middle addition 4ml oleic acid and 7ml octadecylenes, are warming up to 140 DEG C under ar gas environment, stir 1h, obtain solution A；
2) solution A is cooled to room temperature, and the methanol dissolved with 4mmol sodium hydroxides/ammonium fluoride is added dropwise into solution A with peristaltic pump
Solution 10ml, controls the rotating speed of peristaltic pump, and regulation rate of addition is 0.3ml/min, obtains solution B；
3) solution B is warming up to 60 DEG C, vacuumizes removing methanol, is warming up to 280 DEG C under ar gas environment with 10 DEG C/min, instead
60min is answered, oil-soluble NaGd is obtained0.7F4:Yb0.18, Er0.02, Ca0.1Mixed liquor；
4) oil-soluble NaGd0.7F4:Yb0.18, Er0.02, Ca0.1Mixed liquor is cooled to room temperature, adds 3 times of mixeding liquid volumes
Ethanol, 12000rpm centrifugation 5min, obtain oil-soluble NaGd0.7F4:Yb0.18, Er0.02, Ca0.1, washed 3 times, obtained with ethanol
Oil-soluble NaGd0.7F4:Yb0.18, Er0.02, Ca0.1Finished product.It is scattered in 10ml hexane solution.
1.2 prepare NaGd0.7F4:Yb0.18, Er0.02,Ca0.1@NaYb0.9F4:Ca0.1
1) 0.9mmol yttrium acetates, 0.1mmol calcium acetates are weighed, 4ml oleic acid and 7ml octadecylenes are added thereto, in argon gas
140 DEG C are warming up under environment, 1h is stirred, obtains solution C；
2) solution A is cooled to room temperature, and the methanol dissolved with 4mmol sodium hydroxides/ammonium fluoride is added dropwise into solution B with peristaltic pump
Solution 5ml and 10ml NaGd0.7F4:Yb0.18, Er0.02, Ca0.1Hexane solution, control peristaltic pump rotating speed, regulation be added dropwise speed
Spend for 0.3ml/min, obtain solution D；
3) solution D is warming up to 60 DEG C, vacuumizes removing methanol, is warming up to 280 DEG C under ar gas environment with 10 DEG C/min, instead
60min is answered, oil-soluble NaGd is obtained0.7F4:Yb0.18, Er0.02, Ca0.1@NaYb0.9F4:Ca0.1Mixed liquor；
4) oil-soluble NaGd0.7F4:Yb0.18, Er0.02, Ca0.1@NaYb0.9F4:Ca0.1Mixed liquor is cooled to room temperature, adds
The ethanol of 3 times of mixeding liquid volumes, 12000rpm centrifugation 5min, obtains oil-soluble NaGd0.7F4:Yb0.18, Er0.02, Ca0.1@
NaYb0.9F4:Ca0.1, washed with ethanol 3 times, obtain oil-soluble NaGd0.7F4:Yb0.18, Er0.02, Ca0.1@NaYb0.9F4:Ca0.1Into
Product.
1.3 prepare NaGd0.7F4:Yb0.18, Er0.02, Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3, Ca0.1
1) 0.6mmol neodymium acetates are weighed, 0.3mmol gadoliniums, 0.1mmol acetic acid calcium compounds add 4ml oil thereto
Acid and 7ml octadecylenes, are warming up to 140 DEG C under ar gas environment, stir 1h, obtain solution E；
2) solution E is cooled to room temperature, and the methanol dissolved with 4mmol sodium hydroxides/ammonium fluoride is added dropwise into solution E with peristaltic pump
Solution 5ml and 10ml NaGd0.7F4:Yb0.18, Er0.02, Ca0.1Hexane solution, control peristaltic pump rotating speed, regulation be added dropwise speed
Spend for 0.3ml/min, obtain solution F；
3) solution F is warming up to 60 DEG C, vacuumizes removing methanol, is warming up to 280 DEG C under ar gas environment with 10 DEG C/min, instead
60min is answered, oil-soluble NaGd is obtained0.7F4:Yb0.18,Er0.02, Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3, Ca0.1It is mixed
Close liquid；
4) oil-soluble NaGd0.7F4:Yb0.18, Er0.02, Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3, Ca0.1Mixing
Liquid is cooled to room temperature, adds the ethanol of 3 times of mixeding liquid volumes, and 12000rpm centrifugation 5min obtain oil-soluble NaGd0.7F4:
Yb0.18, Er0.02, Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3, Ca0.1, washed with ethanol 3 times, obtain oil-soluble
NaGd0.7F4:Yb0.18, Er0.02, Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3, Ca0.1Finished product.
1.4 prepare NaGd0.7F4:Yb0.18, Er0.02, Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3, Ca0.1@mSiO2
1) 0.1g cetyl trimethylammonium bromides are weighed to be added in 10ml water, are stirred, solution G is formed；Then
It is warming up to 70 DEG C；
2) appropriate NaGd0.68F4:Yb0.2, Er0.02,Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3,Ca0.1Nanometer
The hexane solution of particle is added dropwise to solution G；
3) to above-mentioned middle dropwise addition ethyl acetate, sodium hydroxide (2M), TEOS (100ul) solution, 3h is stirred, Solution H is obtained；
4) after Solution H is centrifuged, water miscible NaGd is obtained0.68F4:Yb0.2, Er0.02,Ca0.1@NaYb0.9F4:Ca0.1@
NaNd0.6F4:Gd0.3,Ca0.1@mSiO2Nano particle；
1.5 prepare NaGd0.7F4:Yb0.18, Er0.02, Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3, Ca0.1@
mSiO2-Rose Bengal
By 0.1g NaGd0.68F4:Yb0.2, Er0.02,Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3,Ca0.1@mSiO2
It is distributed in 5ml water, centrifuges, obtain after adding the 200ul rose-reds aqueous solution (100mg/ml), stirring 24h
NaGd0.68F4:Yb0.2, Er0.02,Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3,Ca0.1@mSiO2- rose-red
Nano particle
Fig. 1 is group of the lanthanides nano particle NaGd prepared by the embodiment of the present invention 10.68F4:Yb0.2, Er0.02,Ca0.1@NaYb0.9F4:
Ca0.1@NaNd0.6F4:Gd0.3,Ca0.1Kernel transmission electron microscope picture (yardstick：50nm)；The size of kernel is probably left in 10nm
It is right.
Fig. 2 is water miscible group of the lanthanides nano particle NaGd prepared by the embodiment of the present invention 10.68F4:Yb0.2, Er0.02,Ca0.1@
NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3,Ca0.1@mSiO2Transmission electron microscope picture；Overall size is probably in 17nm or so, particle diameter
It is homogeneous.
Fig. 3 a are group of the lanthanides nano particle NaGd prepared by the embodiment of the present invention 10.68F4:Yb0.2, Er0.02,Ca0.1@
NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3,Ca0.1@mSiO2Y value is that intensity is relative in x-ray diffraction pattern, Fig. 3 a
Value, the corresponding crystal face of each peak value is as shown in Figure 3 a.The nano particle in the case where near infrared light 980,915,808,780nm are excited,
Produce launch wavelength be 520,550,660nm fluorescence, fluorescence intensity is high, fluorescent stability is good；When erbium is the centre of luminescence, work as erbium
Doping level be 2% when, prepared oil solubility nanometer particle green emitting efficiency highest, as shown in Figure 3 b.
Embodiment 2
NaGd0.73F4:Yb0.2, Er0.02,Ca0.05@NaYb0.95F4:Ca0.05@NaNd0.65F4:Gd0.3,Ca0.05@mSiO2Or
NaGd0.7F4:Yb0.2, Er0.05,Ca0.05@NaYb0.95F4:Ca0.05@NaNd0.65F4:Gd0.3,Ca0.05@mSiO2Also may be used
Prepared according to the similar method of embodiment 1, the particle diameter of oil solubility nanometer particle of the invention by adjust reaction temperature and
Time is regulated and controled, and temperature is higher, the reaction time is longer, and the particle diameter of oil solubility nanometer particle is bigger.
Embodiment 3
A kind of photodynamic therapy system, including medicine module, hyperbaric oxygen supplying module and lighting module are carried, wherein, carry medicine mould
Block is 4T1 tumours, knurl volume is about 100mm3Balbc mouse, what the embodiment 1 that the inside tumor contains 50ul was prepared
Group of the lanthanides nano particle NaGd0.7F4:Yb0.18,Er0.02,Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3,Ca0.1@mSiO2-
Rose Bengal(5mg/ml)；Hyperbaric oxygen supplying module is hyperbaric oxygen chamber, and pressure is 3 atmospheric pressure；Lighting module is 880nm
Laser irradiates.
The method that the group of the lanthanides nano particle prepared using embodiment 1 persistently produces singlet oxygen, step is：Will be above-mentioned
It is 2 hours in the hyperbaric oxygen chamber of 3 atmospheric pressure to carry medicine module and be placed in pressure, while to above-mentioned swollen containing the group of the lanthanides nano particle
Knurl carries out near-infrared laser irradiation (0.75W/cm2, 16min/ times), every other day hyperbaric oxygen once, then irradiation once, experiment
Coprocessing three times in whole cycle, experiment number of days 14 days, observe the production of singlet oxygen, and experimental result is as shown in Figure 4.Figure
4 be the NaGd prepared by the embodiment of the present invention 10.68F4:Yb0.2, Er0.02,Ca0.1@NaYb0.9F4:Ca0.1@NaNd0.6F4:Gd0.3,
Ca0.1@mSiO2Ordinate is DPBF in the standard for the singlet oxygen that-rose-red nano particle is produced under 808nm laser, Fig. 4
(indicator that singlet oxygen is produced) fluorescence intensity relative value, DPBF numerical value declines faster, the generation rate of prompting singlet oxygen
Higher, UCNP+RB+HBO is hyperbaric oxygen group in Fig. 4, and UCNP+RB+Normoxia is normal oxygen group, UCNP+RB+Hypoxia groups
For anoxic group, RB is photosensitizer rose bengal, and UCNP is upconversion fluorescence nano material, figure 4, it is seen that hyperbaric oxygen is handled
The generation rate of singlet oxygen afterwards is most fast, and the singlet oxygen amount produced at 20 minutes is 2 times commonly organized, is the 8.5 of anoxic group
Times.
Tumour is handled and observed using the production method of the photodynamic therapy system and singlet oxygen, Fig. 5 is
Nano particle compares in the targeting conveying effect of the tumour of mouse, and Normal groups are normal pressure group, and HBO groups are hyperbaric oxygen group, can be with
Find out, after 2 hours, cancer target conveying Xiao state of the nano particle of hyperbaric oxygen processing is higher than common group, over time
Extension, until 24 hours, the nano particle of hyperbaric oxygen processing was all higher than common group in the targeting conveying effect of tumour.Fig. 6 is small
The tumor inhibitory effect of mouse.Control groups are PBS groups in Fig. 5, and NIR groups are near infrared light group, and HBO groups are hyperbaric oxygen group,
UCNPs+HBO is up-conversion nano material+hyperbaric oxygen group, and UCNPs+NIR is up-conversion nano material+near infrared light group,
UCNPs+NIR+HBO is up-conversion nano material+near infrared light+hyperbaric oxygen group, it can be seen that be compared to other groups
Not, the tumor killing effect after hyperbaric oxygen processing is far better than other groups, 14 days processing times.
As it will be easily appreciated by one skilled in the art that the foregoing is merely illustrative of the preferred embodiments of the present invention, it is not used to
The limitation present invention, any modifications, equivalent substitutions and improvements made within the spirit and principles of the invention etc., it all should include
Within protection scope of the present invention.
Claims (10)
1. a kind of group of the lanthanides nano particle, it is characterised in that the group of the lanthanides nano particle kernel has sandwich structure, shell is Jie
Hole silicon layer, the chemical composition of the sandwich structure is NaGd(1-x-y-z)F4:Ybx,Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)
F4:Gdt,Caz@mSiO2, wherein 0≤x≤0.3；0≤y≤0.05；0≤z≤0.1；0≤t≤0.4, the thickness of the mesoporous silicon layer
Spend for 2~20nm.
2. group of the lanthanides nano particle as claimed in claim 1, it is characterised in that the average grain diameter of the group of the lanthanides nano particle kernel
For 10~100nm.
3. group of the lanthanides nano particle as claimed in claim 1, it is characterised in that the nano grain surface is adsorbed with sensitising agent,
The sensitising agent is to have the sensitising agent of absorption at 520nm, 550nm or 660nm, preferably rose-red, MC540, methyl blue or
Chlorin.
4. a kind of preparation method of group of the lanthanides nano particle as claimed in claim 1, it is characterised in that comprise the following steps：
1) oleic acid and octadecylene are added into the mixture of gadolinium, yttrium acetate, acetic acid erbium and calcium acetate, in inert gas environment
Under be warming up to 130~160 DEG C, stir 45~60min, obtain solution A；
2) solution A is cooled to 20~30 DEG C, the methanol solution of sodium hydroxide/ammonium fluoride is added dropwise into the solution A, obtains
To solution B；
3) solution B is warming up to 50~70 DEG C, vacuumizes removing methanol, in an inert atmosphere with 5~20 DEG C/min
260~320 DEG C are warming up to, 30~50min is reacted, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx,Ery,CazNano particle is mixed
Liquid；
4) by the oil-soluble NaGd(1-x-y-z)F4:Ybx,Ery,CazNano particle mixed liquor is cooled to 20~30 DEG C, adds 2
The ethanol of~4 times of mixeding liquid volumes, centrifugation obtains oil-soluble NaGd(1-x-y-z)F4:Ybx,Ery,CazNano particle, uses second
Alcohol is washed, and is then dispersed in hexane, is obtained oil-soluble NaGd(1-x-y-z)F4:Ybx,Ery,CazThe hexane solution of nano particle；
5) oleic acid and octadecylene are added into the mixture of yttrium acetate and calcium acetate, it is warming up to 130 in an inert atmosphere~
160 DEG C, 45~60min is stirred, solution C is obtained；
6) solution C is cooled to 20~30 DEG C, into the solution C be added dropwise sodium hydroxide/ammonium fluoride methanol solution and
The NaGd(1-x-y-z)F4:Ybx,Ery,CazThe hexane solution of nano particle, obtains solution D；
7) solution D is warming up to 50~70 DEG C, removing methanol and hexane is vacuumized, in an inert atmosphere with 5~20
DEG C/min is warming up to 260~320 DEG C, 30~50min is reacted, oil-soluble NaGd is obtained(1-x-y-z)F4:Ybx,Ery,Caz@NaYbF4:
CazNano particle mixed liquor；
8) by the oil-soluble NaGd(1-x-y-z)F4:Ybx,Ery,Caz@NaYbF4:CazNano particle mixed liquor is cooled to 20~30
DEG C, the ethanol of 2~4 times of mixeding liquid volumes is added, centrifugation obtains oil-soluble NaGd(1-x-y-z)F4:Ybx,Ery,Caz@NaYbF4:
CazNano particle, is washed with ethanol, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx,Ery,Caz@NaYbF4:CazNano particle into
Product；It is then dispersed in hexane, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx,Ery,Caz@NaYbF4:CazThe hexane of nano particle
Solution；
9) oleic acid and octadecylene are added into the mixture of neodymium acetate, gadolinium and calcium acetate, is heated up in an inert atmosphere
To 130~160 DEG C, 45~60min is stirred, solution E is obtained；
10) solution E is cooled to 20~30 DEG C, into the solution C be added dropwise sodium hydroxide/ammonium fluoride methanol solution and
The NaGd(1-x-y-z)F4:Ybx,Ery,Caz@NaYbF4:CazThe hexane solution of nano particle, obtains solution F；
11) the solution F is warming up to 50~70 DEG C, removing methanol and hexane is vacuumized, in an inert atmosphere with 5~20
DEG C/min is warming up to 260~320 DEG C, 30~50min is reacted, oil-soluble NaGd is obtained(1-x-y-z)F4:Ybx,Ery,Caz@NaYbF4:
Caz@NaNd(1-t-z)F4:Gdt,CazNano particle mixed liquor；
12) by the oil-soluble NaGd(1-x-y-z)F4:Ybx,Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,CazNanometer
Grain mixed liquor is cooled to 20~30 DEG C, adds the ethanol of 2~4 times of mixeding liquid volumes, and centrifugation obtains oil-soluble NaGd(1-x-y-z)
F4:Ybx,Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,CazNano particle, is washed with ethanol, obtains oil-soluble
NaGd(1-x-y-z)F4:Ybx,Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,CazNano particle finished product, is washed with ethanol,
It is then dispersed in hexane, obtains oil-soluble NaGd(1-x-y-z)F4:Ybx,Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,
CazThe hexane solution of nano particle；
13) take cetyl trimethylammonium bromide to be added to the water, stir 0.5~2 hour, form solution G, then raise temperature to 60
~80 DEG C；
14) by the NaGd(1-x-y-z)F4:Ybx,Ery,Caz@NaYbF4:Caz@NaNd(1-t-z)F4:Gdt,CazNano particle oneself
Alkane solution, which is added dropwise under the solution G, stirring condition, to react 0.5~48 hour；Then ethyl acetate, sodium hydroxide and 50 is added dropwise
Reacted 2~8 hours under~300ul TEOS, stirring condition, obtain Solution H；After the Solution H is centrifuged, obtaining right such as will
Seek the group of the lanthanides nano particle described in 1.
5. the application of a kind of group of the lanthanides nano particle as described in claims 1 to 3 any one, it is characterised in that applied to system
The medicine of standby treatment tumour.
6. a kind of method that utilization group of the lanthanides nano particle persistently produces singlet oxygen, it is characterised in that will be as claimed in claim 3
Group of the lanthanides nano particle be placed in high pressure oxygen environment, while to the group of the lanthanides nano particle carry out near-infrared laser irradiation.
7. method as claimed in claim 6, it is characterised in that the high pressure oxygen environment is provided by hyperbaric oxygen chamber.
8. method as claimed in claim 6, it is characterised in that the wavelength of the near-infrared laser be 980nm, 915nm,
808nm or 780nm.
9. method as claimed in claim 6, it is characterised in that the time being placed in high pressure oxygen environment is 30min~4h/
Secondary, the pressure of the hyperbaric oxygen is more than 1 atmospheric pressure, but no more than 3 atmospheric pressure.
10. a kind of photodynamic therapy system, it is characterised in that the photodynamic therapy system includes following module：Load medicine module,
Hyperbaric oxygen supplying module and lighting module；
Wherein, the load medicine module is used for carrying medicament；The medicine is preferably group of the lanthanides nano particle as claimed in claim 3
Load sensitising agent；
The hyperbaric oxygen supplying module is used to provide high pressure oxygen to the load medicine module, and the load medicine module is placed in the high pressure
In the high pressure oxygen environment that oxygen supply module is provided；
The lighting module is used to provide illumination to the load medicine module, the medicine is persistently produced singlet under light illumination
Oxygen.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108096586A (en) * | 2017-12-05 | 2018-06-01 | 上海大学 | Double-bang firecracker based on manganese dioxide modification answers preparation method, product and the application of drug delivery system |
| CN110987583A (en) * | 2019-11-25 | 2020-04-10 | 中国人民解放军第四军医大学 | Method for detecting MC540 singlet oxygen yield by using SOSG |
| CN111892927A (en) * | 2020-05-08 | 2020-11-06 | 天津大学 | Preparation method and application of up-conversion nanorod |
| CN112451862A (en) * | 2020-11-24 | 2021-03-09 | 深圳罗兹曼国际转化医学研究院 | Photodynamic therapy system and control method thereof |
-
2017
- 2017-05-24 CN CN201710373050.8A patent/CN107137709B/en active Active
Non-Patent Citations (3)
| Title |
|---|
| MATZI V.等: ""Photodynamic therapy enhanced by hyperbaric oxygenation in palliation of malignant pleural mesothelioma: clinical experience"", 《PHOTODIAGN. PHOTODYN. THER.》 * |
| NIAGARA MUHAMMAD IDRIS等: ""Upconversion nanoparticles as versatile light nanotransducers for photoactivation applications"", 《CHEM. SOC. REV.》 * |
| YAN ZHANG等: ""Ultrasmall-Superbright NeodymiumUpconversion Nanoparticles via Energy Migration Manipulation and Lattice Modification: 808 nm-Activated Drug Release"", 《ACS NANO》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108096586A (en) * | 2017-12-05 | 2018-06-01 | 上海大学 | Double-bang firecracker based on manganese dioxide modification answers preparation method, product and the application of drug delivery system |
| CN110987583A (en) * | 2019-11-25 | 2020-04-10 | 中国人民解放军第四军医大学 | Method for detecting MC540 singlet oxygen yield by using SOSG |
| CN110987583B (en) * | 2019-11-25 | 2022-05-13 | 中国人民解放军第四军医大学 | Method for detecting MC540 singlet oxygen yield by using SOSG |
| CN111892927A (en) * | 2020-05-08 | 2020-11-06 | 天津大学 | Preparation method and application of up-conversion nanorod |
| CN112451862A (en) * | 2020-11-24 | 2021-03-09 | 深圳罗兹曼国际转化医学研究院 | Photodynamic therapy system and control method thereof |
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