CN1977999A - Method for selectively killing cells utilizing ultraviolet conversion luminous nano particles - Google Patents
Method for selectively killing cells utilizing ultraviolet conversion luminous nano particles Download PDFInfo
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- CN1977999A CN1977999A CN 200510123022 CN200510123022A CN1977999A CN 1977999 A CN1977999 A CN 1977999A CN 200510123022 CN200510123022 CN 200510123022 CN 200510123022 A CN200510123022 A CN 200510123022A CN 1977999 A CN1977999 A CN 1977999A
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- ultraviolet
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Abstract
The present invention relates to a method capable of utilizing ultraviolet up-conversion granules to selectively kill cells, and is characterized by that it uses the ultraviolet up-conversion nano granules capable of sending ultraviolet light under the irradiation of infrared light or visible light, makes the antibody capable of implementing specific combination with target cell be connected on said nano granule surface and utilizes the characteristics of that said antibody and cell surface correspondent antigen can make selectively combination so as to implement selective combination of nano granules and target cells, then it adopts infrared light or ultraviolet light to irradiate the ultraviolet up-conversion luminous nano granules so as to kill the cells combined with ultraviolet light sent by said ultraviolet up-conversion granules.
Description
Technical field:
The invention belongs to and utilize ultraviolet light to kill cell method and technology field, particularly utilize the method for ultraviolet conversion luminous nano particles selectively killing cells.
Background technology:
Utilizing ultraviolet light to kill cell is a kind of widely used technology.The 24th page of " Medical Microbiology " (Qian Lisheng chief editor) who publishes as publishing house of Fudan University 2003 is pointed, and this class technology is to utilize ultraviolet light killing the destruction realization pair cell of dna construct.When utilizing ultraviolet to kill cell, ultraviolet light all has fragmentation effect to the cell in the illuminated scope.But sometimes we wish only to kill some specific cell and do not influence around other cell, and existing ultraviolet light is killed cell technology and can not be accomplished this point.In addition, because the ultraviolet light penetration capacity is limited, limited ultraviolet light in the application of killing aspect the organism inner cell.
Ultraviolet conversion luminous material can produce ultraviolet light under infrared or visible light radiation.People can prepare this class material of nano-scale in recent years.Holland's " optical communication " (optics communications, the 242nd phase, the 215th page) introduced a kind of method for preparing rear-earth-doped nano-sized particles, and this nano-particle can be launched ultraviolet light under infrared or visible light radiation.But yet there are no the report that the ultraviolet light that utilizes this nano-particle emission is killed cell so far.
By nano-particle is carried out finishing, utilize immunologic principle, make nano-particle and target cell realize optionally combining, this is full-fledged in recent years a special kind of skill.Britain's " Nature Biotechnol " (nature biotechnology, the 22nd volume, the 969-976 page or leaf) and Holland's " contemporary viewpoint of biotechnology " (Current Opinion in Biotechnology, the 16th volume, 63-72 page or leaf) introduced the progress of this respect.But what generally use in the prior art is fluorescent nano particle.So far do not see the report that makes ultraviolet conversion luminous nano particles and target cell realize the selective binding aspect as yet.
Summary of the invention:
The present invention proposes a kind of method of utilizing conversion nano granule on the ultraviolet to realize the pair cell selectively killing, and it is limited and cause particularly killing deficiency aspect the organism inner cell killing cell to overcome the ultraviolet light penetration capacity to a certain extent.
The present invention utilizes the method for ultraviolet conversion luminous nano particles selectively killing cells, it is characterized in that: use at the nano-particle that can launch ultraviolet light under infrared or the radiation of visible light---conversion nano granule on the ultraviolet, by connecting at this nano grain surface and can realizing the bonded antibody of specificity with target cell, utilize the bonded characteristics of the corresponding selection of antigen of antibody, realize that nano-particle optionally combines with target cell with cell surface; Then, the ultraviolet conversion luminous nano particles luminescent material for emission ultraviolet light under the infrared light irradiation adopts the infrared light irradiation; Or the ultraviolet conversion luminous nano particles luminescent material for emission ultraviolet light under radiation of visible light then adopts radiation of visible light; Thereby realize utilizing ultraviolet light the killing of conversion nano granule emission on the ultraviolet to combined cell.
Described at the nano-particle that can launch ultraviolet light under infrared or the radiation of visible light---conversion nano granule on the ultraviolet, mix weight concentration in the substrate and be no more than 30% rare earth ion and realize ultraviolet conversion luminous material under infrared or radiation of visible light, producing all types of nano-particle of wavelength, being included in less than 300 nano-ultraviolet lights; Described substrate comprises fluoride LaF
3, K
2YF
3Or Zn
0.3Al
0.25Pb
0.3Li
0.098Yb
0.1F
2.354, or oxide Y
2O
3, CaAl
4O
7Or SrAl
4O
7, described rare earth ion comprises Tm
3+, Ho
3+, Yb
3+, pr
3+Or Er
3+Described ultraviolet conversion luminous nano particles also comprises can realize ultraviolet conversion luminous various semiconductor-quantum-points, comprises semi-conducting material ZnS, ZnO or the GaN of broad stopband.
Describedly can realize the bonded antibody of specificity with cell, be to utilize antibody and the bonded characteristic of antigenic specificity, for different cells according to they the different selected corresponding antibody of antigen in surface.
Prior art is normally directly killed irradiated cell with irradiation under ultraviolet ray, and so ultraviolet light will be killed the various cells that are irradiated in the irradiation area, pair cell kill the shortage specific selectivity; And in the inventive method since the ultraviolet light that is used for killing cell by with the bonded ultraviolet of cell on the conversion nano granule produce, the limited ultraviolet light of these penetration capacitys only has lethal effect to the particulate cell of combining nano, and less to other impact cell, this has just reached the purpose of selectively killing cells.On the other hand, because the ultraviolet light penetration capacity is limited, existing method only is applicable to the cell of killing body surface or near surface; And what shine in the inventive method is infrared or visible light, and its penetration capacity is better than ultraviolet light.Especially infrared light is even also there is good penetration depth in biological tissue.So just the scope of application that ultraviolet light is killed cell is widened in the organism from organism surface; And infrared and visible light does not have injury effect substantially to most biological tissues, thereby can adopt high-energy-density irradiation, it is limited and cause particularly killing deficiency aspect the organism inner cell killing cell that this overcomes the ultraviolet light penetration capacity to a certain extent.
The specific embodiment:
Embodiment 1: in the leukocyte and lymphocytic two class cells that mix, kill the former under the situation that does not injure the latter.
Specific practice is as follows:
At first prepare ultraviolet conversion luminous nano particles.Method is: be immersed in Zn in the ethanol with the Nd:YAG pulsed laser irradiation
0.3Al
0.25Pb
0.3Li
0.098Yb
0.1Tm
0.002F
2.354Glass, this glass prepares with solid-state reaction.Prepared granular size depends on the burst length of laser instrument.More detailed preparation information can be with reference to Dutch magazine " optical communication " (opticscommunications, the 242nd phase, the 215th page).
Be to realize prepared nano-particle and leukocytic selective binding below: at first will form suspension in the nano-particle adding ammonia that prepare, this suspension is centrifugal 10 minutes with 5000 rev/mins, remove supernatant, sonic oscillation is 15 minutes under the low temperature, adds glutaraldehyde then, stirring at room 20 minutes, centrifugal 10 minutes with 5000 rev/mins, remove supernatant, with the PBS liquid washing of pH7.6, reuse PBS disperses.Mouse-anti people CD45Pur PBS is added in the dispersive nano granule suspension, and 4 degrees centigrade of low temperature stirred 24 hours, with PBS liquid washed product, were stored in 4 degrees centigrade of refrigerators standby.
The preparation of cell sample: get anticoagulant venous blood 2ml in sterile tube, shake up, the aseptic Hanks liquid that adds equivalent, with in the desk type high speed refrigerated centrifuger under 1000 rev/mins rotating speed centrifugal 10 minutes, take out centrifuge tube and go the supernatant, add 5 times of erythrocyte cracked liquids to the blood cell volume, effect is 15 minutes in 37 degrees centigrade of calorstats, the an amount of normal saline centrifuge washing of reuse 2 times is 1000 rev/mins at every turn, and (available leukocyte theoretical value was 0.8～2 * 10 in centrifugal 10 minutes
7Individual cells/ml, its medium-sized lymphocyte accounts for 20%～30%), and then be diluted to 1 * 10 with Hanks liquid
6～10 * 10
6Individual cells/ml is stand-by.Be the preparation of antigen sheet below.Get clean slide, drip a cell suspension respectively, dry up fast, fix 10 minutes with pure acetone under 4 degrees centigrade with cold wind, with 0.1% gelatin sealing 10 minutes, dry section, absorb excess liquid, add ultraviolet conversion luminous nano particles after CD45 modifies on microscope slide with filter paper, put into wet box then, the box that will wet again places 37 degrees centigrade of biochemical incubator constant temperature to cultivate 1 hour, takes out the back and washes 3 times each 5 minutes with PBS solution.Through above-mentioned steps, ultraviolet conversion luminous nano particles optionally has been adsorbed onto on the leukocyte.
At last, be the laser irradiation cell of 798 nanometers with wavelength, utilize the ultraviolet light of bonded ultraviolet conversion luminous nano particles emission on the leukocyte to kill leukocyte.Because ultraviolet penetration capacity is very limited, so do not have can not come to harm in conjunction with the lymphocyte of ultraviolet conversion luminous nano particles.
Embodiment 2: to suffering from the mice of tumor, do not injuring kill tumor cell under the Normocellular situation.
Specific practice is as follows:
Still use the ultraviolet conversion luminous nano particles among the embodiment 1.To the surface treatment of this nano-particle also with example 1.
Nano-particle after monoclonal antibody J591 and the processing was reacted two hours under PH8, and the amount of used antibody is 20 times (mol ratios) of nano-particle.With product high speed centrifugation 30 minutes, the PBS liquid of reuse PH7 disperseed then.Advance above-mentioned steps, just prepared the surperficial nano-particle that is connected with antibody J591.
Above-mentioned nano-particle is injected the tail vein of the mice that suffers from tumor.After one hour, be that the infrared light of 798 nanometers shines this mice with wavelength.Infrared light can penetrate several centimetres in biological tissue, so under the irradiation of above-mentioned infrared light, the intravital ultraviolet conversion luminous nano particles of mice can produce ultraviolet light.Because selected antibody can optionally combine with TCSA, so nano-particle only is adsorbed on surface of tumor cells, thereby the ultraviolet light that they produce only has lethal effect to tumor cell again.
In practical situation, may need to kill the cell of other types, this need change the antibody that is adsorbed on the ultraviolet conversion luminous nano particles surface into the antibody corresponding with the cell of wanting to kill with regard to passable.Select for use which type of antibody can be referring to " Medical Immunology " (Gong Fei advocates to compile, and Science Press published in 2004).The irradiation light wavelength of using depends on concrete ultraviolet conversion luminous material, and certainly, because the selected material of the inventive method itself, the irradiation light wavelength is always in the scope of infrared and visible light.Because infrared light and visible light pair cell be injury not, so can use the rayed of higher-strength.
Claims (3)
1, a kind of method of utilizing the ultraviolet conversion luminous nano particles selectively killing cells, it is characterized in that: use at the nano-particle that can launch ultraviolet light under infrared or the radiation of visible light---conversion nano granule on the ultraviolet, by connecting at this nano grain surface and can realizing the bonded antibody of specificity with target cell, utilize the bonded characteristics of the corresponding selection of antigen of antibody, realize that nano-particle optionally combines with target cell with cell surface; Then, the ultraviolet conversion luminous nano particles luminescent material for emission ultraviolet light under the infrared light irradiation adopts the infrared light irradiation; Or the ultraviolet conversion luminous nano particles luminescent material for emission ultraviolet light under radiation of visible light then adopts radiation of visible light; Thereby realize utilizing ultraviolet light the killing of conversion nano granule emission on the ultraviolet to combined cell.
2, utilize the method for ultraviolet conversion luminous nano particles selectively killing cells according to claim 1, be characterised in that: described at the nano-particle that can launch ultraviolet light under infrared or the radiation of visible light---conversion nano granule on the ultraviolet, mix weight concentration in the substrate and be no more than 30% rare earth ion and realize ultraviolet conversion luminous material under infrared or radiation of visible light, producing all types of nano-particle of wavelength, being included in less than 300 nano-ultraviolet lights; Described substrate comprises fluoride LaF
3, K
2YF
3Or Zn
0.3Al
0.25Pb
0.3Li
0.098Yb
0.1F
2.354, or oxide Y
2O
3, CaAl
4O
7Or SrAl
4O
7, described rare earth ion comprises Tm
3+, Ho
3+, Yb
3+, Pr
3+Or Er
3+Described ultraviolet conversion luminous nano particles also comprises can realize ultraviolet conversion luminous various semiconductor-quantum-points, comprises semi-conducting material ZnS, ZnO or the GaN of broad stopband.
3, utilize the method for ultraviolet conversion luminous nano particles selectively killing cells according to claim 1, be characterised in that: describedly can realize the bonded antibody of specificity with cell, be to utilize antibody and the bonded characteristic of antigenic specificity, for different cells according to they the different selected corresponding antibody of antigen in surface.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510123022 CN1977999A (en) | 2005-12-09 | 2005-12-09 | Method for selectively killing cells utilizing ultraviolet conversion luminous nano particles |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510123022 CN1977999A (en) | 2005-12-09 | 2005-12-09 | Method for selectively killing cells utilizing ultraviolet conversion luminous nano particles |
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| Publication Number | Publication Date |
|---|---|
| CN1977999A true CN1977999A (en) | 2007-06-13 |
Family
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|---|---|---|---|
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103131412A (en) * | 2013-02-05 | 2013-06-05 | 河北大学 | Visible-ultraviolet up-conversion luminescent material BaGd2ZnO5: Er3+, preparation method thereof and application thereof |
| CN103439242A (en) * | 2013-09-06 | 2013-12-11 | 华南师范大学 | Microfluidic system and method for detecting and screening single beam biological cells |
| CN105676517A (en) * | 2016-03-22 | 2016-06-15 | 成都京东方光电科技有限公司 | Quantum dot film and display device |
-
2005
- 2005-12-09 CN CN 200510123022 patent/CN1977999A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103131412A (en) * | 2013-02-05 | 2013-06-05 | 河北大学 | Visible-ultraviolet up-conversion luminescent material BaGd2ZnO5: Er3+, preparation method thereof and application thereof |
| CN103439242A (en) * | 2013-09-06 | 2013-12-11 | 华南师范大学 | Microfluidic system and method for detecting and screening single beam biological cells |
| CN103439242B (en) * | 2013-09-06 | 2016-05-11 | 华南师范大学 | Microfluidic system and method that a kind of single beam biological cell detects and screens |
| CN105676517A (en) * | 2016-03-22 | 2016-06-15 | 成都京东方光电科技有限公司 | Quantum dot film and display device |
| US10203527B2 (en) | 2016-03-22 | 2019-02-12 | Boe Technology Group Co., Ltd. | Quantum dot film and display device |
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