CN106963949A - Application of the polyethyleneglycol modified magnetic microsphere in tumour near infrared light thermal agent is prepared - Google Patents
Application of the polyethyleneglycol modified magnetic microsphere in tumour near infrared light thermal agent is prepared Download PDFInfo
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- CN106963949A CN106963949A CN201710297808.4A CN201710297808A CN106963949A CN 106963949 A CN106963949 A CN 106963949A CN 201710297808 A CN201710297808 A CN 201710297808A CN 106963949 A CN106963949 A CN 106963949A
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- 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
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
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Abstract
The invention belongs to technical field of biological materials, the application of specially polyethyleneglycol modified magnetic microsphere in tumour near infrared light thermal agent is prepared.The magnetic microsphere of PEG modifications, it has stronger absorption in near-infrared region, and the near infrared light of absorption can be converted into heat so that tumour cell is killed in the rise of tumor locus local temperature, available for the photothermal reagent for preparing near infrared light heat cure.Compared compared with photothermal reagent, magnetic microsphere good biocompatibility, degradable, size is easy to regulation and control, and magnetic saturation intensity is higher, be widely used in biomedical sector, therefore with high clinical value.
Description
Technical field
The invention belongs to technical field of biological materials, and in particular to prepared by the magnetic microsphere of polyethylene glycol (PEG) modification
Application near infrared light hot-cast socket reagent, the near infrared light heat cure for tumour.
Background technology
Cancer just turns into the biggest threat of harm human life and health.The mode of current treating cancer mainly has operation to control
Treatment, chemotherapy, radiation treatment, but operative treatment is very difficult to except cancer cells all in vivo, chemotherapy has toxic side effect, and
The drug resistance of cancer cell is easily induced, radiation treatment is easily destroyed the immune system of human body.And photo-thermal therapy is a kind of emerging
The high selectivity and minimal invasive techniques for treating cancer, by photothermal reagent local near-infrared laser irradiate, it is nearly red
Outer energy conversion is heat energy, so as to effective killing tumor cell.
In recent years, people, which study more photothermal reagent, mainly has metal_based material, carbon-based material, copper sulfide etc. are inorganic to receive
Rice material and with nir dye, with the organic nano material for representative such as polymer.Although these materials are small in lotus knurl
Relatively good effect is achieved in mouse body, but these materials are because cost is high, preparation process is complicated and needs to carry out largely
Surface modification, hamper their further clinical conversions.Therefore, develop a kind of with low cost, simple efficiently and biological
The good photo-thermal reagent of compatibility is significant for following clinical tumor photo-thermal therapy.
Magnetic iron oxide particles are due to its good biological safety, and size easy-regulating is easily separated, magnetic saturation intensity it is high with
And the advantages of superparamagnetism, be widely used in biomedical (clinical diagnosis, enzyme mark, targeted drug), cytology (cell marking,
Cell separation etc.) and the field such as bioengineering (enzyme immobilizatio).Various sizes of magnetic microsphere can be synthesized using hydro-thermal method.
Up to the present, the magnetic microsphere of PEG modifications, pays close attention on its physicochemical property few people, and is developed as near-infrared
Photothermal deformation reagent and be even more seldom report for the photo-thermal therapy of tumour.
The content of the invention
The purpose of the present invention is exactly that there is provided PEG in order to solve problem present in above-mentioned tumor thermal therapy（Poly- second two
Alcohol）The magnetic microsphere of modification is applied in the photothermal reagent for preparing treatment tumour.The photothermal reagent is cheap, simple efficient
And biocompatibility is good.
In the present invention, the magnetic microsphere main component of described PEG modifications is Fe3O4Nano-particle, its particle size range 100 ~
Between 500 nm, and with stronger absorption between 700 ~ 1000nm of near infrared wavelength region.
In the present invention, the magnetic microsphere of described PEG modifications can select the PEG of different molecular weight（Molecular weight is 400 ~ 1
×104）The magnetic microsphere of modification, for preparing near infrared light hot-cast socket reagent.Concrete outcome is as follows：
The magnetic microsphere of the PEG modifications of measured amounts, is made into the solution that concentration is 50 μ g/mL respectively, and ultrasonic disperse takes 200 μ
L sample is placed in 96 orifice plates；With 808nm laser illumination, while the temperature for recording sample solution with infrared thermography becomes
Change situation.Pass through near infrared light Thermal test, it was demonstrated that the magnetic microsphere of PEG modifications has preferable photo-thermal effect.
Based on above-mentioned characteristic, the magnetic microsphere of PEG proposed by the present invention modification can in preparing near infrared light hot-cast socket reagent,
And for the near infrared light heat cure of tumour；The concentration of the magnetic microsphere of PEG modifications is 50 ~ 500 μ g/mL.
In the present invention, PEG molecular weight is 400 ~ 1 × 104。
In the present invention, the magnetic microsphere of PEG modifications proposed by the present invention is prepared by hydro-thermal method.
Compared with prior art, the magnetic microsphere of PEG modifications of the present invention has advantages below：
（1）Synthetic method is simple, and cheap；
（2）Photo-thermal conversion efficiency is high, light and heat stability；
（3）Biological safety can be ensured in good biocompatibility, human body.
Brief description of the drawings
Fig. 1 is the transmission electron microscope picture for the magnetic microsphere that PEG of the present invention the is modified, (unit of engineer's scale 100：Nanometer, nm).
Fig. 2 is the X ray diffracting spectrum for the magnetic microsphere that PEG of the present invention is modified.
Fig. 3 is the hysteresis curve collection of illustrative plates for the magnetic microsphere that PEG of the present invention is modified.
Fig. 4 is the uv-visible absorption spectra for the magnetic microsphere various concentrations solution that PEG of the present invention is modified.
Fig. 5 is that the magnetic microsphere various concentrations solution of PEG of the present invention modification in power output is 6.6 W/cm2, wavelength is
808 nm laser, the Continuous irradiation temperature variation curve of 5 minutes.
Fig. 6 is that the magnetic microsphere that PEG of the present invention is modified acts on human embryonic kidney cells (293T) toxotest figure.
Fig. 7 is that the magnetic microsphere that PEG of the present invention is modified acts on Non-small cell lung carcinoma cell (A549) toxotest figure.
Embodiment
Embodiment 1：The preparation of the magnetic microsphere of PEG modifications
Weigh FeCl3·6H2The g of O 1.08 are scattered in 40.0 mL ethylene glycol, after the min of ultrasonic disperse 10, add 1.0 g's
After PEG (Mw=2000) and the g of sodium acetate 1.20, the min of ultrasonic disperse 10, by mixed liquor high speed magnetic stirring at ambient temperature
0.5 h, forms uniform brown suspension.Then the mixed liquor of above-mentioned gained is transferred to 50 mL hydro-thermal autoclave
In, it is 200 to be put into temperatureoIn C high temperature oven, taken out after 10 h of reaction.Reactor is washed away with chilled water flow, makes its quick
It is cooled to room temperature.Resulting product is removed, Magneto separate product is successively repeatedly washed with ethanol and deionized water, and will production
Thing is scattered stand-by in deionized water, obtains the magnetic microsphere of product PEG modifications.
Embodiment 2：
The magnetic microsphere of the PEG modifications of measured amounts, is made into after the 100 μ g/mL aqueous solution, ultrasonic disperse, sampling is placed in stone
In English cuvette, suction of the magnetic microsphere in 400 ~ 1000nm wave bands of a certain amount of PEG modifications is tested with ultraviolet specrophotometer
Receipts situation.As a result as shown in figure 4, the magnetic microsphere of PEG of the present invention modifications has stronger UV absorption in near-infrared region.
Embodiment 3：
The magnetic microsphere of the PEG modifications of measured amounts is made into after 50 μ g/mL solution, ultrasonic disperse in water, takes 200 μ L
Sample is placed in 96 orifice plates.With 808nm laser illumination, while recording the temperature change of sample solution with infrared thermography
Situation.As a result as shown in figure 5, being 6.6W/cm in power2Laser irradiation under, in 5 minutes, 50 μ g/mL sample temperature difference
Increase 52.2 DEG C.
Embodiment 4：
The magnetic microsphere of the PEG modifications of measured amounts is made into 5 ~ 1000 μ g/mL photothermal deformation reagent, so in culture medium
Itself and 293T cells are carried out afterwards to be incubated 24 h, then the survival rate for detecting cell is tested by tetramethyl azo azoles salt (MTT).Figure
6 be the corresponding cytotoxic effect figure of embodiment 3, and when concentration reaches 1000 μ g/mL, 293T cell survival rates are still 80%
More than, illustrate the toxicity very little of the magnetic microsphere of PEG modifications, with preferable biocompatibility.
Embodiment 5：
The magnetic microsphere of the PEG modifications of measured amounts is made into 100 μ g/mL photothermal deformation reagent in culture medium, then will
Itself and the h of A549 cell incubations 2, using 808nm, power is 6.6 W/cm2Laser illumination different time, then pass through MTT
Method detects the survival rate of cell.
Fig. 7 is the corresponding photo-thermal effect figure of embodiment 4, and when light application time is 300s, A549 cell survival rates are reduced to
Less than 15.1%, illustrate that the photo-thermal effect of the magnetic microsphere of PEG modifications is very good, can be effective by stronger photothermy
Tumour cell is killed, with good tumor thermal therapy prospect.
Claims (4)
1. PEG is repaiied in application of the polyethyleneglycol modified magnetic microsphere in tumour near infrared light thermal agent is prepared, photothermal reagent
The concentration of the magnetic microsphere of decorations is 50 ~ 500 μ g/mL.
2. application according to claim 1, it is characterised in that the magnetic microsphere main component of described PEG modifications is
Fe3O4Nano-particle, its particle size range has between 100 ~ 600nm, and between 700 ~ 1000nm of near infrared wavelength region
Stronger absorption.
3. application according to claim 1 or 2, it is characterised in that PEG point in the magnetic microsphere of described PEG modifications
Son amount is 400 ~ 1 × 104。
4. according to claim 1 or described application, it is characterised in that described photothermal reagent is prepared from by hydro-thermal method.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107677817A (en) * | 2017-08-29 | 2018-02-09 | 山东师范大学 | A kind of salmonella typhimurium quick determination method based on immune magnetic Nano material photo-thermal effect |
| CN109395100A (en) * | 2018-08-02 | 2019-03-01 | 贵州医科大学 | A kind of construction method of scutellarin magnetic Nano drug-loading system and application |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103341165A (en) * | 2013-05-31 | 2013-10-09 | 上海师范大学 | Fe@Fe3O4 nanoparticles having photothermal function, and preparation method and application thereof |
| CN103721256A (en) * | 2012-10-15 | 2014-04-16 | 北京大学 | Near infrared photo-thermal conversion agent for tumor photo-thermal excision treatment |
-
2017
- 2017-04-29 CN CN201710297808.4A patent/CN106963949A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103721256A (en) * | 2012-10-15 | 2014-04-16 | 北京大学 | Near infrared photo-thermal conversion agent for tumor photo-thermal excision treatment |
| CN103341165A (en) * | 2013-05-31 | 2013-10-09 | 上海师范大学 | Fe@Fe3O4 nanoparticles having photothermal function, and preparation method and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| 袁罡: ""聚乙二醇化 Fe3O4作为光热治疗剂对大鼠 C6 胶质瘤细胞光热治疗的可行性研究"", 《中国博士学位论文数据库-医药卫生科技辑》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107677817A (en) * | 2017-08-29 | 2018-02-09 | 山东师范大学 | A kind of salmonella typhimurium quick determination method based on immune magnetic Nano material photo-thermal effect |
| CN109395100A (en) * | 2018-08-02 | 2019-03-01 | 贵州医科大学 | A kind of construction method of scutellarin magnetic Nano drug-loading system and application |
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