CN109464663A - A kind of preparation method and applications of the light thermit powder with target function - Google Patents
A kind of preparation method and applications of the light thermit powder with target function Download PDFInfo
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- CN109464663A CN109464663A CN201811256071.2A CN201811256071A CN109464663A CN 109464663 A CN109464663 A CN 109464663A CN 201811256071 A CN201811256071 A CN 201811256071A CN 109464663 A CN109464663 A CN 109464663A
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- 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
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Abstract
The present invention provides a kind of preparation methods of light thermit powder with target function.This method have it is convieniently synthesized, it is low in cost, the characteristics of asepsis environment-protecting.The present invention mainly uses biocompatibility excellent and nontoxic albumen is as stabilizer and reacting environment, and the Bi of albumen cladding is prepared as targeting factor in the folic acid to target to specific tumors cell2S3The dispersion liquid is obtained the dispersion liquid of its purer complex microsphere by dialysis by nanoparticle dispersion liquid.Final products obtained have good photo-thermal therapy effect, can be used for targeting photo-thermal therapy.
Description
Technical field
The present invention relates to material science and bio-medical field, specially a kind of biocompatibility is excellent with targeting function
The preparation and application of the light thermit powder of energy.
Background technique
All the time, cancer is all the hot subject that biomedical families are studied.Traditional anti-cancer therapies include hand
Art treatment, chemotherapy, radiotherapy etc..Often all there are some defects in these treatment means, such as unavoidably
The damage of normal tissue, drug resistance, the uncertainty for the treatment of etc..
Photo-thermal therapy (PTT) is a kind of advanced oncotherapy technology, and for the technology with its accurate positioning, toxic side effect is small,
Therapeutic effect is significant and is increasingly becoming the hot spot in oncotherapy technology.The technology utilizes the material with high light thermal conversion efficiency
Material is enriched with it in tumor region by EPR effect, then near infrared light by it by being injected intravenously in organism
(NIR) thermal energy is converted light energy under irradiation to kill cancer cell.It, should since NIR has stronger tissue penetration
There are the damage very little of means normal tissue biggish potentiality to be applied in oncotherapy.
As the n-type semiconductor (≈ 1.3eV) of direct strip gap, bismuth sulfide (Bi2S3) nanoparticle is since its is higher
Near-infrared absorption was applied to the photo-thermal therapy of tumour in recent years.However, common synthetic method complex steps, react item
Part requires ligand that is high and being easily introduced bio-toxicity.Therefore, develop it is a kind of it is easy, mild, bio-compatible is excellent and economy has
The strategy of effect prepares the Bi for PTT2S3Nanoparticle is particularly important.In order to improve the transfer efficiency of drug, targeting factor must
It is indispensable.Introducing in photo-thermal therapy has the effect of that the targeting factor of target function can significantly improve treatment to tumour.
Based on this, the light thermit powder with excellent biocompatibility and with target function is prepared with important by easy method
Research significance.
Summary of the invention
The present invention provides a kind of preparation methods of light thermit powder with target function.This method have it is convieniently synthesized, at
The characteristics of this is cheap, asepsis environment-protecting.
The present invention provides the preparation method of the light thermit powder with target function, specifically includes the following steps:
(1) using trivalent bismuth salt and albumen as raw material, under acidic aqueous solution environment, protein molecular and bismuth ion are in certain item
It is complexed under part, obtains the complex compound of albumen and bismuth ion.
(2) complex reaction liquid pH is adjusted in (1) to alkalinity, the abundant reaction bismuth sulfide for preparing albumen cladding under certain condition
Nanoparticle.
(3) the targeting factor folic acid (FA) of activated carboxylic is added in the reaction solution of (2), after sufficiently being reacted under certain condition
Obtain the bismuth sulfide nano particle of folic acid grafted protein modification.Unreacted albumen and small molecule are filtered off by dialysis again, obtained
The dispersion liquid of complex microsphere.
Based on the above technical solution, the present invention can also have following further specific choice or more preferably select
It selects.
Preferably, in step (1), the trivalent bismuth salt is one of five nitric hydrate bismuths, bismuth chloride；Albumen is ox
One kind of haemocyanin (BSA) and human albumin (HSA)；The molar concentration of trivalent bismuth salt is 0.0045-0.0055mM；Albumen
Mass concentration be 20-30mg/mL；Acid condition is pH ≈ 3-5；Certain condition is mechanical stirring 0.5-1h at room temperature.
Specifically, pH is adjusted to 11-13 in step (2)；Certain condition is 37 DEG C of mechanical stirring 6-8h.
Specifically, FA mass concentration is 0.33-0.39mg/mL in step 3；Certain condition is to be protected from light lower mechanical stirring 10-
12h；Described that molecular cut off is used to dialyse in deionized water three days for the bag filter of 100000D, every 6-8h changes a water.
It is compared to the prior art, the positive effect of the present invention is as follows:
(1) albumen that this research uses biocompatibility excellent and nontoxic is as stabilizer and reacting environment, to specific
The folic acid of tumour cell targeting is as targeting factor, obtained Bi2S3Nanoparticle has good photo-thermal therapy effect, can use
It is a kind of nano material that can be applied to treatment of cancer with very big potential using value in targeting photo-thermal therapy.
(2) due to the cladding of albumen, Bi2S3It the uniform particle diameter of nanoparticle and has good stability, is suitably applied organism
It is interior.
(3) raw material sources used in the present invention are extensive, low in cost, and preparation method is easy, assay reproducibility
Height is easy to subsequent popularization and application.
Detailed description of the invention
Fig. 1 is the transmission electron microscope picture for the functional microsphere prepared；
Fig. 2 is the Uv-Vis absorption spectrum comparison diagram of folic acid grafting front and back；
Fig. 3 is the change curve of the functional microsphere temperature prepared with irradiation time.
Specific embodiment
Below in conjunction with specific embodiments and the drawings, the present invention is further described in detail, and example is served only for solving
The present invention is released, is not intended to limit the scope of the present invention.
There is the functional microsphere of good photo-thermal effect and targeting using method provided by the invention preparation, detailed process is such as
Following example 1 is to shown in 5.The drug without specific instruction used in embodiment is street drug, is used in embodiment
It is conventional method that method, which does not elaborate,.
Embodiment one
(1) use 10mL deionized water dissolving in 50ml single port bottle for 0.25g bovine serum albumin (BSA) first.Then will
Five nitric hydrate bismuth of 0.024g is dissolved in 1mL nitric acid (2M) solution, is then slowly added drop-wise to list under conditions of magnetic agitation
In mouth bottle.One hour of complex reaction, obtains complex compound BSA-Bi under the conditions of 37 DEG C3+。
(2) pH to 12 of solution is adjusted with the sodium hydroxide solution of 2M, then the magnetic agitation 6h under 37 DEG C of reaction temperatures,
Obtain the bismuth sulfide nano particle of albumen cladding.
(3) the 10mg folic acid activated is dissolved in 2mL DMSO, is then slowly added drop-wise in reaction solution, in the item being protected from light
Under part, room temperature magnetic agitation reacts 10h, obtains the bismuth sulfide nano particle dispersion of folic acid grafted protein modification.End of reaction
Selecting molecular cut off afterwards is that the bag filter of 100000D is protected from light dialysis three days, removes and filters off unreacted albumen and small molecule,
Obtain the dispersion liquid of more pure complex microsphere.
Fig. 1 is that the freeze-drying sample 1mg in this example deposits in 5mL plastic centrifuge tube and 4mL deionized water is added, ultrasound
Disperse 10min, is then added dropwise on copper mesh, to parch naturally, is observed using the transmission electron microscope of model TecnaiG20.
Test results are shown in figure 1, it can be found that functional microsphere can be uniformly dispersed Yu Shuizhong, uniform particle diameter.
Fig. 2 is folic acid grafting front and back Uv-Vis abosrption spectrogram in this example.Bi2S3The curve of@BSA-FA is 360nm's
Characteristic peak shows that targeting factor folic acid is successfully grafted.
It is 808nm, energy density 1.5W/cm that Fig. 3, which is with wavelength,2Laser irradiation dispersion liquid and control group, and measure not
With the variation of its temperature of period, it is seen that the functional microsphere that the present invention prepares has preferable photo-thermal effect: about 180s
Irradiation time can be warming up to 45 DEG C or more, and with the growth of irradiation time, temperature can also continue to increase, can play kill it is swollen
The effect of oncocyte has great potential using value.
Embodiment two
(1) use 10mL deionized water dissolving in 50ml single port bottle for 0.25g bovine serum albumin (BSA) first.Then will
0.017g bismuth chloride is dissolved in 1mL nitric acid (2M) solution, is then slowly added drop-wise in single port bottle under conditions of magnetic agitation.
Complex reaction 0.5 hour, obtains complex compound BSA-Bi under the conditions of 37 DEG C3+。
(2) pH to 12 of solution is adjusted with the sodium hydroxide solution of 2M, then the magnetic agitation 8h under 37 DEG C of reaction temperatures,
Obtain the bismuth sulfide nano particle of albumen cladding.
(3) the 10mg folic acid activated is dissolved in 2mL DMSO, is then slowly added drop-wise in reaction solution, in the item being protected from light
Under part, room temperature magnetic agitation reacts 10h, obtains the bismuth sulfide nano particle dispersion of folic acid grafted protein modification.End of reaction
Selecting molecular cut off afterwards is that the bag filter of 100000D is protected from light dialysis three days, removes and filters off unreacted albumen and small molecule,
Obtain the dispersion liquid of more pure complex microsphere.
Embodiment three
(1) use 10mL deionized water dissolving in 50ml single port bottle for 0.25g human albumin (HSA) first.Then will
Five nitric hydrate bismuth of 0.024g is dissolved in 1mL nitric acid (2M) solution, is then slowly added drop-wise to list under conditions of magnetic agitation
In mouth bottle.Complex reaction 0.5 hour, obtains complex compound HSA-Bi under the conditions of 37 DEG C3+。
(2) pH to 11 of solution is adjusted with the sodium hydroxide solution of 2M, then the magnetic agitation 8h under 37 DEG C of reaction temperatures,
Obtain the bismuth sulfide nano particle of albumen cladding.
(3) the 10mg folic acid activated is dissolved in 2mL DMSO, is then slowly added drop-wise in reaction solution, in the item being protected from light
Under part, room temperature magnetic agitation reacts 12h, obtains the bismuth sulfide nano particle dispersion of folic acid grafted protein modification.End of reaction
Selecting molecular cut off afterwards is that the bag filter of 100000D is protected from light dialysis three days, removes and filters off unreacted albumen and small molecule,
Obtain the dispersion liquid of more pure complex microsphere.
Example IV
(1) use 10mL deionized water dissolving in 50ml single port bottle for 0.20g human albumin (HSA) first.Then will
0.017g bismuth chloride is dissolved in 1mL nitric acid (2M) solution, is then slowly added drop-wise in single port bottle under conditions of magnetic agitation.
Complex reaction 1 hour, obtains complex compound HSA-Bi under the conditions of 37 DEG C3+。
(2) pH to 12 of solution is adjusted with the sodium hydroxide solution of 2M, then the magnetic agitation 6h under 37 DEG C of reaction temperatures,
Obtain the bismuth sulfide nano particle of albumen cladding.
(3) the 10mg folic acid activated is dissolved in 2mL DMSO, is then slowly added drop-wise in reaction solution, in the item being protected from light
Under part, room temperature magnetic agitation reacts 10h, obtains the bismuth sulfide nano particle dispersion of folic acid grafted protein modification.End of reaction
Selecting molecular cut off afterwards is that the bag filter of 100000D is protected from light dialysis three days, removes and filters off unreacted albumen and small molecule,
Obtain the dispersion liquid of more pure complex microsphere.
Embodiment five
(1) use 10mL deionized water dissolving in 50ml single port bottle for 0.25g bovine serum albumin (BSA) first.Then will
Five nitric hydrate bismuth of 0.024g is dissolved in 1mL nitric acid (2M) solution, is then slowly added drop-wise to list under conditions of magnetic agitation
In mouth bottle.Complex reaction 0.5 hour, obtains complex compound BSA-Bi under the conditions of 37 DEG C3+。
(2) pH to 13 of solution is adjusted with the sodium hydroxide solution of 2M, then the magnetic agitation 8h under 37 DEG C of reaction temperatures,
Obtain the bismuth sulfide nano particle of albumen cladding.
(3) the 10mg folic acid activated is dissolved in 2mL DMSO, is then slowly added drop-wise in reaction solution, in the item being protected from light
Under part, room temperature magnetic agitation reacts 12h, obtains the bismuth sulfide nano particle dispersion of folic acid grafted protein modification.End of reaction
Selecting molecular cut off afterwards is that the bag filter of 100000D is protected from light dialysis three days, removes and filters off unreacted albumen and small molecule,
Obtain the dispersion liquid of more pure complex microsphere.
The foregoing is merely presently preferred embodiments of the present invention, is not intended to limit the invention, it is all in spirit of the invention and
Within principle, any modification, equivalent replacement, improvement and so on be should all be included in the protection scope of the present invention.
Claims (7)
1. a kind of preparation method of the light thermit powder with target function, which is characterized in that comprise the steps of:
(1) using appropriate trivalent bismuth salt and albumen as raw material, under acidic aqueous solution environment, protein molecular and bismuth ion are in certain item
It is complexed under part, obtains the complex compound of albumen and bismuth ion.
(2) complex reaction liquid pH is adjusted in (1) to alkalinity, the abundant reaction bismuth sulfide nano for preparing albumen cladding under certain condition
Particle.
(3) folic acid after appropriate activation is dissolved in dimethyl sulfoxide, is then slowly added drop-wise in the reaction solution of step (2),
The bismuth sulfide nano particle dispersion of folic acid grafted protein modification is obtained after sufficiently reacting under certain condition.It is filtered off again by dialysis
Unreacted albumen and small molecule obtain the dispersion liquid of complex microsphere.
2. a kind of preparation method of light thermit powder with target function according to claim 1, which is characterized in that step
(1) in, the trivalent bismuth salt is one of five nitric hydrate bismuths or bismuth chloride.
3. a kind of preparation method of light thermit powder with target function according to claim 1, which is characterized in that step
(1) in, the albumen is one kind of bovine serum albumin (BSA) or human albumin (HSA).
4. a kind of preparation method of light thermit powder with target function according to claim 1, which is characterized in that step
(1) in, the molar concentration of the trivalent bismuth salt is 0.0045-0.0055mM；The mass concentration of albumen is 20-30mg/mL；Institute
The pH value for stating acidic aqueous solution is 3-5；The certain condition is the mechanical stirring 0.5-1h at 37 DEG C.
5. a kind of preparation method of light thermit powder with target function according to claim 1, which is characterized in that step
(2) in, the pH is adjusted to 11-13；The certain condition is the mechanical stirring 6-8h at 37 DEG C.
6. a kind of preparation method of light thermit powder with target function according to claim 1, which is characterized in that step
(3) in, the mass concentration of folic acid is 0.33-0.39mg/mL；The certain condition is, under conditions of being protected from light, room temperature magnetic force is stirred
Mix reaction 10h；The dialysis procedure is specially to use molecular cut off for 100000D the bismuth sulfide nano particle dispersion
Bag filter dialyse in deionized water three days, every 6-8h changes a water.
7. a kind of preparation method of light thermit powder with target function according to claim 1, which is characterized in that step
(3) in, the folic acid after the activation takes 10mg, and the dimethyl sulfoxide takes 2mL.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110193087A (en) * | 2019-06-12 | 2019-09-03 | 山西医科大学 | A kind of tumor microenvironment response type diagnosis and treatment integration nano-probe and preparation method thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104876266A (en) * | 2015-04-21 | 2015-09-02 | 南京邮电大学 | Aqueous-phase preparation method of bismuth sulfide/protein composite nanospheres |
| CN107551279A (en) * | 2017-09-14 | 2018-01-09 | 苏州大学 | Extra small albumen composite nano-granule near infrared light fuel factor and multi-modality imaging function and its preparation method and application |
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2018
- 2018-10-26 CN CN201811256071.2A patent/CN109464663A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104876266A (en) * | 2015-04-21 | 2015-09-02 | 南京邮电大学 | Aqueous-phase preparation method of bismuth sulfide/protein composite nanospheres |
| CN107551279A (en) * | 2017-09-14 | 2018-01-09 | 苏州大学 | Extra small albumen composite nano-granule near infrared light fuel factor and multi-modality imaging function and its preparation method and application |
Non-Patent Citations (2)
| Title |
|---|
| QUNLIAN HUANG ET AL: "Albumin-assisted exfoliated ultrathin rhenium disulfide nanosheets as a tumor targeting and dual-stimuli-responsive drug delivery system for a combination chemo-photothermal treatment", 《RSC ADVANCES》 * |
| YONG WANG ET AL: "BSA-Mediated Synthesis of Bismuth Sulfide Nanotheranostic Agents for Tumor Multimodal Imaging and Thermoradiotherapy", 《ADV. FUNCT. MATER.》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110193087A (en) * | 2019-06-12 | 2019-09-03 | 山西医科大学 | A kind of tumor microenvironment response type diagnosis and treatment integration nano-probe and preparation method thereof |
| CN110193087B (en) * | 2019-06-12 | 2022-02-08 | 山西医科大学 | Tumor microenvironment response type diagnosis and treatment integrated nanoprobe and preparation method thereof |
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Application publication date: 20190315 |