CN105148271A - Near-infrared light stimulation controllably responsive photo-thermal microcapsule having thermal therapy/chemotherapy double actions and preparation method of microcapsule - Google Patents
Near-infrared light stimulation controllably responsive photo-thermal microcapsule having thermal therapy/chemotherapy double actions and preparation method of microcapsule Download PDFInfo
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Abstract
The invention relates to a near-infrared light stimulation controllably responsive photo-thermal microcapsule having thermal therapy/chemotherapy double actions and a preparation method of the microcapsule, wherein the chemical formula of the microcapsule is shown as MEO2MA/MEO2MA-co-OEGMA-CuS-DOX. The preparation method comprises the following steps: (1) dissolving sodium dodecyl benzene sulfonate and polyethylene glycol dimethacrylate; and (2) dissolving MEO2MA in a solution obtained from the step (1), filling nitrogen, heating up and polymerizing so as to obtain an M colloidal nucleus solution; adding MEO2MA, OEGMA, an emulsifier and a cross-linking agent, filling nitrogen, heating up and polymerizing so as to obtain M/MO microgel; adding copper sulfate pentahydrate, heating up and adding an ammonium sulfide solution so as to obtain M/MO-CuS from reaction; dissolving DOX in a phosphate buffered solution of the M/MO-CuS, stirring, centrifuging and dialyzing so as to obtain the microcapsule. The method disclosed by the invention is low in cost, mild in reaction condition and strong in controllability, and photo-thermal conversion nanoparticles are small in particle size and are uniformly distributed.
Description
Technical field
The invention belongs to photic hot microcapsule and preparation field thereof, particularly a kind of near infrared light with thermotherapy/chemotherapy dual function stimulates photic hot microcapsule of controlled response and preparation method thereof.
Background technology
The health of the cancer serious threat mankind, in current tumor therapeuticing method, chemotherapy application is comparatively extensive.Chemotherapy process needs medicine to be enriched in tumor site with finite concentration within the specific time.But common chemotherapeutic treatment cycle is long, drug effect position is not concentrated, poor controllability, its side effect are large, is difficult to meet the demand of effectively curing cancer.For this reason, emphasis is concentrated on preparation by large quantity research stimulates the drug carrier material with response to outfield.But these outfield stimulus often need large-area stimulation field stimulation, easily have side effects.The absorption of light to water and/or biological tissue of the wave-length coverage of near infrared light (NIR) from 700 to 1100nm is few, and can reach and go deep into affected area by transdermal tissue, have no side effect generation.Therefore, near infrared light thermal therapeutical tumor technology gets more and more people's extensive concerning.The near infrared light hot material developed at present comprises noble metal, material with carbon element and organic optothermal material, and semiconductor light hot material.In order to improve photo-thermal therapy effect further, photo-thermal/chemotherapy combined treatment technology receives much concern, and has developed multiplely to comprise for therapeutic alliance reagent: polyaniline/PNIPAM; The Jenner's grain of rice/PNIPAM-acrylic acid; Graphene/silicon dioxide/PNIPAM-acrylic acid (Nanotechnology2014,25,495602; Nanoscale2014,6,8743; Nat.Mater.2009,8,935; J.Am.Chem.Soc.2014,136,7317) but these therapeutic alliance reagent are difficult to the medicine be loaded into the release realizing controllable precise.For this reason, explore and develop and a kind of there is the treatment reagent that near infrared light stimulates controlled response, effective thermotherapy/chemotherapy double treatment can be carried out to tumor, not have side effects simultaneously, substantially increase therapeutic efficiency.Thus there is prior using value.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of near infrared light with thermotherapy/chemotherapy dual function stimulates photic hot microcapsule of controlled response and preparation method thereof, the method can be applicable to effectively melting tumor cell, reduces side effect greatly simultaneously.
A kind of near infrared light with thermotherapy/chemotherapy dual function of the present invention stimulates the photic hot microcapsule of controlled response, and the chemical formula of described microcapsule is MEO
2mA/MEO
2mA-co-OEGMA-CuS-DOX.
The near infrared light with thermotherapy/chemotherapy dual function stimulates a preparation method for the photic hot microcapsule of controlled response, comprising:
(1) dodecylbenzene sodium sulfonate and polyethylene glycol dimethacrylate are dissolved in deionized water; Wherein, the concentration of dodecylbenzene sodium sulfonate is 1.5-1.8mmol/L, and the concentration of polyethylene glycol dimethacrylate is 0.25-0.30mmol/L;
(2) by 2-methyl-2 acrylic acid-2-(2-methoxy ethoxy) ethyl ester MEO
2mA is dissolved in the solution that step (1) obtains, and passes into nitrogen and is warming up to 60-90 DEG C, adding initiator, polyreaction 4-6 hour, centrifugal, and dialysis, obtains polymethacrylates PMEO
2mA microgel glue core solution, i.e. M glue core solution; Wherein MEO2MA concentration is in the solution 20-25mmol/L;
(3) MEO is added in the M glue core solution obtained in step (2)
2mA, oligomeric ethylene glycol methyl ether methacrylate OEGMA, emulsifying agent and cross-linking agent, pass into nitrogen temperature to 60-90 DEG C, add initiator, polyreaction 6-8h, centrifugal, dialysis, forms P (MEO at M glue core skin
2mA-co-OEGMA) polymeric outer layer MO shell, obtains polyethylene glycol methacrylate-styrene polymer MEO
2mA/MEO
2mA-co-OEGMA nucleocapsid structure microgel, i.e. M/MO microgel; Wherein, MEO
2the amount of the monomeric substance of MA and OEGMA is than being 40-50:10-15, and the concentration of emulsifying agent is 1.5-1.8mmol/L, and the concentration of cross-linking agent is 0.5-0.6mmol/L;
(4) in the M/MO microgel solution described in step (3), copper sulphate pentahydrate stirring at normal temperature 3-5 hour is added; Add ammonium sulfide solution after being warming up to 60-90 DEG C, under stirring condition, carry out reaction 4-6 hour; By gained solution centrifugal also by washed with de-ionized water, nano-copper sulfide composite microgel material MEO can be obtained
2mA/MEO
2mA-co-OEGMA-CuS, the i.e. nano combined microgel of M/MO-CuS; Wherein the mass ratio of copper sulphate pentahydrate and ammonium sulfide is 3:1-3.5:1; M/MO microgel solution is 10-30:1 with the amount of substance ratio of anhydrous cupric sulfate;
(5) doxorubicin hydrochloride is dissolved in the phosphate buffered solution containing the nano combined microgel of M/MO-CuS, stirs 24-48 hour; Centrifugal, dialysis, obtains M/MO-CuS-DOX capsule of nano, i.e. MEO
2mA/MEO
2the photic hot microcapsule of the controlled response of MA-co-OEGMA-CuS-DOX; Wherein the mass ratio of DOX and nano-copper sulfide composite microgel material is that the amount of substance of 1:100-1:10, DOX and M/MO-CuS nano-complex is than being 1:10-100.
In described step (1), dodecylbenzene sodium sulfonate is as emulsifying agent, and polyethylene glycol dimethacrylate is as cross-linking agent.
In described step (3), emulsifying agent is dodecylbenzene sodium sulfonate.
In described step (3), cross-linking agent is polyethylene glycol dimethacrylate.
MEO in described step (3)
2the concentration of MA is the concentration of 40-50mmol/L, OEGMA is 10-15mmol/L.
Described step (2) and the middle initiator of step (3) are potassium peroxydisulfate.
The concentration of described step (2) and the middle initiator of step (3) is 0.5-0.7mmol/L.
Described step (4) copper sulphate pentahydrate adds in solution under room temperature, and stirring at normal temperature 3-5 hour, object is to allow Cu
2+be adsorbed in M/MO microgel in the mode of coordination.
The speed stirred after adding ammonium sulfide solution in described step (4) is 300rpm.
The speed stirred in described step (5) is 100rpm.
Centrifugal in described step (5), the doxorubicin hydrochloride DOX of unentrapped is removed in dialysis.
The photic hot microcapsule of the controlled response obtained in described step (5) is applied near infrared light thermal therapeutical, the controllable release of medicine, the heat/chemotherapy of tumor.
Preparation method of the present invention have with low cost, reaction condition is gentle, controllability is strong, photothermal deformation nano particle diameter is little and the feature such as to be evenly distributed.The microencapsulation material with the controlled response of photo-thermal prepared by this kind of method, can the controlled intensification the temperature range of 25-57 DEG C under near infrared light, produces thermotherapy effect in affected area; Meanwhile, under temperature controls, microgel material volume shrinks, and the drug controllable release of being carried by bag, in affected area, reaches thermotherapy/chemotherapy double therapeutic effect.
beneficial effect
(1) the present invention has prepared the near infrared light with thermotherapy/chemotherapy dual function stimulates the photic hot microencapsulation material of controlled response, this material is under near infrared light, photothermal deformation nanoparticle raised temperature in microcapsule, produces thermotherapy effect in affected area; Meanwhile, under temperature controls, microgel generation controlled volume is shunk, and by controlled the discharging of medicine that inside bag carries, produces chemotherapy effect in affected area;
(2) the present invention adopts and first prepares nucleocapsid structure microgel, again in the preparation scheme of microgel situ grow light hot-cast socket nanoparticle, and use hydrothermal reaction at low temperature to prepare photothermal deformation nanoparticle, photothermal deformation nanoparticle can be made to obtain less particle diameter, higher specific surface area and better distributing homogeneity, thus effectively can improve the photo-thermal conversion efficiency of nanoparticle;
(3) heat/chemotherapy dual function that the near infrared light that prepared by the present invention stimulates the photic hot microencapsulation material of controlled response to bring effectively can carry out controlled melting to tumor cell, and by regulating laser intensity and irradiation time to carry out the accurate control of switch to release amount of medicine and rate of release, be better than single photo-thermal therapy or the therapeutic effect of chemotherapy, reduce the side effect in therapeutic process simultaneously;
(4) the present invention adopts microgel monomer used to have good biocompatibility, and uses nano-copper sulfide as photothermal deformation nanoparticle, with low cost, temperature-controllable good, has high practicality.
Accompanying drawing explanation
Fig. 1 is the MEO obtained in embodiment 1
2mA/MEO
2the TEM figure of MA-co-OEGMA-CuS.
Detailed description of the invention
Below in conjunction with specific embodiment, set forth the present invention further.Should be understood that these embodiments are only not used in for illustration of the present invention to limit the scope of the invention.In addition should be understood that those skilled in the art can make various changes or modifications the present invention, and these equivalent form of values fall within the application's appended claims limited range equally after the content of having read the present invention's instruction.
Embodiment 1
The first step: dodecylbenzene sodium sulfonate and polyethylene glycol dimethacrylate are dissolved in deionized water; Wherein the concentration of dodecylbenzene sodium sulfonate is 1.5mmol/L, and the concentration of polyethylene glycol dimethacrylate is 0.25mmol/L;
Second step: by 2-methyl-2-acrylic acid-2-(2-methoxy ethoxy) ethyl ester (MEO
2mA) be dissolved in above-mentioned solution, MEO
2mA concentration is 20mmol/L; Pass into nitrogen and be warming up to 60 DEG C; Add potassium peroxydisulfate, concentration is 0.5mmol/L; Carry out polyreaction 6 hours, eccentric cleaning 3 times, dialyse 3 days, preparation M glue core;
3rd step: add MEO in M glue core solution
2mA, oligomeric ethylene glycol methyl ether methacrylate (OEGMA), dodecylbenzene sodium sulfonate (emulsifying agent) and polyethylene glycol dimethacrylate (cross-linking agent), concentration is respectively 40mmol/L, 10mmol/L, 1.5mmol/L, 0.5mmol/L; Pass into nitrogen and be warming up to 60 DEG C; Add initiator potassium persulfate, concentration is 0.5mmol/L; Carry out polyreaction after 8 hours, eccentric cleaning 3 times, dialyse 3 days, obtained M/MO microgel solution;
4th step: add copper sulphate pentahydrate stirring at normal temperature 3 hours in M/MO microgel solution, add ammonium sulfide solution after being warming up to 60 DEG C; The mass ratio of copper sulphate pentahydrate and ammonium sulfide is 3:1, carries out low-temperature epitaxy react 6 hours with the rotating speed of 300rpm;
5th step: by gained solution centrifugal also by washed with de-ionized water, 3 times repeatedly, dialyse 3 days, obtain nano-copper sulfide composite microgel material;
6th step: by nano-copper sulfide composite microgel material and doxorubicin hydrochloride mixed dissolution in phosphate buffered solution, stir 48 hours with the rotating speed of 100rpm, wherein the mass ratio of doxorubicin hydrochloride and nano-copper sulfide composite microgel material is 1:100; Centrifugal, dialysis after obtain the photic hot microcapsule of controlled response, after its 915nm wavelength laser by 2.0W irradiates 5 minutes, temperature is elevated to 60 DEG C.
The MEO that the present embodiment prepares
2mA/MEO
2the TEM figure of MA-co-OEGMA-CuS as shown in Figure 1.
Embodiment 2
The first step: dodecylbenzene sodium sulfonate and polyethylene glycol dimethacrylate are dissolved in deionized water; Wherein the concentration of dodecylbenzene sodium sulfonate is 1.8mmol/L, and the concentration of polyethylene glycol dimethacrylate is 0.30mmol/L;
Second step: by 2-methyl-2-acrylic acid-2-(2-methoxy ethoxy) ethyl ester (MEO
2mA) be dissolved in above-mentioned solution, MEO
2mA concentration is 25mmol/L; Pass into nitrogen and be warming up to 90 DEG C; Add potassium peroxydisulfate, concentration is 0.7mmol/L; Carry out polyreaction 4 hours, eccentric cleaning 3 times, dialyse 3 days, preparation M glue core;
3rd step: add MEO in M glue core solution
2mA, oligomeric ethylene glycol methyl ether methacrylate (OEGMA), dodecylbenzene sodium sulfonate (emulsifying agent) and polyethylene glycol dimethacrylate (cross-linking agent), concentration is respectively 50mmol/L, 15mmol/L, 1.8mmol/L, 0.6mmol/L; Pass into nitrogen and be warming up to 90 DEG C; Add initiator potassium persulfate, concentration is 0.7mmol/L; Carry out polyreaction after 6 hours, eccentric cleaning 3 times, dialyse 3 days, obtained M/MO microgel solution;
4th step: add copper sulphate pentahydrate stirring at normal temperature 5 hours in M/MO microgel solution, add ammonium sulfide solution after being warming up to 90 DEG C; The mass ratio of copper sulphate pentahydrate and ammonium sulfide is 3.5:1, carries out low-temperature epitaxy react 4 hours with the rotating speed of 300rpm;
5th step: by gained solution centrifugal also by washed with de-ionized water, 3 times repeatedly, dialyse 3 days, obtain nano-copper sulfide composite microgel material;
6th step: by nano-copper sulfide composite microgel material and doxorubicin hydrochloride mixed dissolution in phosphate buffered solution, stir 48 hours with the rotating speed of 100rpm, wherein the mass ratio of doxorubicin hydrochloride and nano-copper sulfide composite microgel material is 1:10; Centrifugal, dialysis after obtain the photic hot microcapsule of controlled response, after its 915nm wavelength laser by 2.0W irradiates 3 minutes, temperature is elevated to 65 DEG C.
Embodiment 3
The first step: dodecylbenzene sodium sulfonate and polyethylene glycol dimethacrylate are dissolved in deionized water; Wherein the concentration of dodecylbenzene sodium sulfonate is 1.6mmol/L, and the concentration of polyethylene glycol dimethacrylate is 0.28mmol/L;
Second step: by 2-methyl-2-acrylic acid-2-(2-methoxy ethoxy) ethyl ester (MEO
2mA) be dissolved in above-mentioned solution, MEO
2mA concentration is 22mmol/L; Pass into nitrogen and be warming up to 70 DEG C; Add potassium peroxydisulfate, concentration is 0.6mmol/L; Carry out polyreaction 5 hours, eccentric cleaning 3 times, dialyse 3 days, preparation M glue core;
3rd step: add MEO in M glue core solution
2mA, oligomeric ethylene glycol methyl ether methacrylate (OEGMA), dodecylbenzene sodium sulfonate (emulsifying agent) and polyethylene glycol dimethacrylate (cross-linking agent), concentration is respectively 45mmol/L, 13mmol/L, 1.6mmol/L, 0.53mmol/L; Pass into nitrogen and be warming up to 80 DEG C; Add initiator potassium persulfate, concentration is 0.6mmol/L; Carry out polyreaction after 5 hours, eccentric cleaning 3 times, dialyse 3 days, obtained M/MO microgel solution;
4th step: add copper sulphate pentahydrate stirring at normal temperature 4 hours in M/MO microgel solution, add ammonium sulfide solution after being warming up to 90 DEG C; The mass ratio of copper sulphate pentahydrate and ammonium sulfide is 3.25:1, carries out low-temperature epitaxy react 5 hours with the rotating speed of 300rpm;
5th step: by gained solution centrifugal also by washed with de-ionized water, 3 times repeatedly, dialyse 3 days, obtain nano-copper sulfide composite microgel material;
6th step: by nano-copper sulfide composite microgel material and doxorubicin hydrochloride mixed dissolution in phosphate buffered solution, stir 48 hours with the rotating speed of 100rpm, wherein the mass ratio of doxorubicin hydrochloride and nano-copper sulfide composite microgel material is 1:50; Centrifugal, dialysis after obtain the photic hot microcapsule of controlled response, after its 915nm wavelength laser by 2.0W irradiates 4 minutes, temperature is elevated to 55 DEG C.
Embodiment 4
The first step: dodecylbenzene sodium sulfonate and polyethylene glycol dimethacrylate are dissolved in deionized water; Wherein the concentration of dodecylbenzene sodium sulfonate is 1.65mmol/L, and the concentration of polyethylene glycol dimethacrylate is 0.26mmol/L;
Second step: by 2-methyl-2-acrylic acid-2-(2-methoxy ethoxy) ethyl ester (MEO
2mA) be dissolved in above-mentioned solution, MEO
2mA concentration is 24mmol/L; Pass into nitrogen and be warming up to 80 DEG C; Add potassium peroxydisulfate, concentration is 0.55mmol/L; Carry out polyreaction 4 hours, eccentric cleaning 3 times, dialyse 3 days, preparation M glue core;
3rd step: add MEO in M glue core solution
2mA, oligomeric ethylene glycol methyl ether methacrylate (OEGMA), dodecylbenzene sodium sulfonate (emulsifying agent) and polyethylene glycol dimethacrylate (cross-linking agent), concentration is respectively 48mmol/L, 14mmol/L, 1.7mmol/L, 0.58mmol/L; Pass into nitrogen and be warming up to 80 DEG C; Add initiator potassium persulfate, concentration is 0.58mmol/L; Carry out polyreaction after 7 hours, eccentric cleaning 3 times, dialyse 3 days, obtained M/MO microgel solution;
4th step: add copper sulphate pentahydrate stirring at normal temperature 5 hours in M/MO microgel solution, add ammonium sulfide solution after being warming up to 80 DEG C; The mass ratio of copper sulphate pentahydrate and ammonium sulfide is 3.4:1, carries out low-temperature epitaxy react 5 hours with the rotating speed of 300rpm;
5th step: by gained solution centrifugal also by washed with de-ionized water, 3 times repeatedly, dialyse 3 days, obtain nano-copper sulfide composite microgel material;
6th step: by nano-copper sulfide composite microgel material and doxorubicin hydrochloride mixed dissolution in phosphate buffered solution, stir 48 hours with the rotating speed of 100rpm, wherein the mass ratio of doxorubicin hydrochloride and nano-copper sulfide composite microgel material is 1:80; Centrifugal, dialysis after obtain the photic hot microcapsule of controlled response, after its 915nm wavelength laser by 2.0W irradiates 5 minutes, temperature is elevated to 55 DEG C.
Embodiment 5
The first step: dodecylbenzene sodium sulfonate and polyethylene glycol dimethacrylate are dissolved in deionized water; Wherein the concentration of dodecylbenzene sodium sulfonate is 1.7mmol/L, and the concentration of polyethylene glycol dimethacrylate is 0.27mmol/L;
Second step: by 2-methyl-2-acrylic acid-2-(2-methoxy ethoxy) ethyl ester (MEO
2mA) be dissolved in above-mentioned solution, MEO
2mA concentration is 23mmol/L; Pass into nitrogen and be warming up to 90 DEG C; Add potassium peroxydisulfate, concentration is 0.56mmol/L; Carry out polyreaction 5 hours, eccentric cleaning 3 times, dialyse 3 days, preparation M glue core;
3rd step: add MEO in M glue core solution
2mA, oligomeric ethylene glycol methyl ether methacrylate (OEGMA), dodecylbenzene sodium sulfonate (emulsifying agent) and polyethylene glycol dimethacrylate (cross-linking agent), concentration is respectively 44mmol/L, 11mmol/L, 1.7mmol/L, 0.53mmol/L; Pass into nitrogen and be warming up to 80 DEG C; Add initiator potassium persulfate, concentration is 0.53mmol/L; Carry out polyreaction after 6 hours, eccentric cleaning 3 times, dialyse 3 days, obtained M/MO microgel solution;
4th step: add copper sulphate pentahydrate stirring at normal temperature 3 hours in M/MO microgel solution, add ammonium sulfide solution after being warming up to 70 DEG C; The mass ratio of copper sulphate pentahydrate and ammonium sulfide is 3:1, carries out low-temperature epitaxy react 4 hours with the rotating speed of 300rpm;
5th step: by gained solution centrifugal also by washed with de-ionized water, 3 times repeatedly, dialyse 3 days, obtain nano-copper sulfide composite microgel material;
6th step: by nano-copper sulfide composite microgel material and doxorubicin hydrochloride mixed dissolution in phosphate buffered solution, stir 48 hours with the rotating speed of 100rpm, wherein the mass ratio of doxorubicin hydrochloride and nano-copper sulfide composite microgel material is 1:40; Centrifugal, dialysis after obtain the photic hot microcapsule of controlled response, after its 915nm wavelength laser by 2.0W irradiates 3 minutes, temperature is elevated to 60 DEG C.
Embodiment 6
The first step: dodecylbenzene sodium sulfonate and polyethylene glycol dimethacrylate are dissolved in deionized water; Wherein the concentration of dodecylbenzene sodium sulfonate is 1.6mmol/L, and the concentration of polyethylene glycol dimethacrylate is 0.29mmol/L;
Second step: by 2-methyl-2-acrylic acid-2-(2-methoxy ethoxy) ethyl ester (MEO
2mA) be dissolved in above-mentioned solution, MEO
2mA concentration is 21mmol/L; Pass into nitrogen and be warming up to 60 DEG C; Add potassium peroxydisulfate, concentration is 0.68mmol/L; Carry out polyreaction 4 hours, eccentric cleaning 3 times, dialyse 3 days, preparation M glue core;
3rd step: add MEO in M glue core solution
2mA, oligomeric ethylene glycol methyl ether methacrylate (OEGMA), dodecylbenzene sodium sulfonate (emulsifying agent) and polyethylene glycol dimethacrylate (cross-linking agent), concentration is respectively 41mmol/L, 14mmol/L, 1.7mmol/L, 0.58mmol/L; Pass into nitrogen and be warming up to 70 DEG C; Add initiator potassium persulfate, concentration is 0.58mmol/L; Carry out polyreaction after 6 hours, eccentric cleaning 3 times, dialyse 3 days, obtained M/MO microgel solution;
4th step: add copper sulphate pentahydrate stirring at normal temperature 3 hours in M/MO microgel solution, add ammonium sulfide solution after being warming up to 80 DEG C; The mass ratio of copper sulphate pentahydrate and ammonium sulfide is 3.5:1, carries out low-temperature epitaxy react 6 hours with the rotating speed of 300rpm;
5th step: by gained solution centrifugal also by washed with de-ionized water, 3 times repeatedly, dialyse 3 days, obtain nano-copper sulfide composite microgel material;
6th step: by nano-copper sulfide composite microgel material and doxorubicin hydrochloride mixed dissolution in phosphate buffered solution, stir 48 hours with the rotating speed of 100rpm, wherein the mass ratio of doxorubicin hydrochloride and nano-copper sulfide composite microgel material is 1:60; Centrifugal, dialysis after obtain the photic hot microcapsule of controlled response, after its 915nm wavelength laser by 2.0W irradiates 5 minutes, temperature is elevated to 65 DEG C.
Claims (10)
1. the near infrared light with thermotherapy/chemotherapy dual function stimulates the photic hot microcapsule of controlled response, it is characterized in that, the chemical formula of described microcapsule is MEO
2mA/MEO
2mA-co-OEGMA-CuS-DOX.
2. the near infrared light with thermotherapy/chemotherapy dual function stimulates a preparation method for the photic hot microcapsule of controlled response, comprising:
(1) dodecylbenzene sodium sulfonate and polyethylene glycol dimethacrylate are dissolved in deionized water; Wherein, the concentration of dodecylbenzene sodium sulfonate is 1.5-1.8mmol/L, and the concentration of polyethylene glycol dimethacrylate is 0.25-0.30mmol/L;
(2) by 2-methyl-2 acrylic acid-2-(2-methoxy ethoxy) ethyl ester MEO
2mA is dissolved in the solution that step (1) obtains, and passes into nitrogen and is warming up to 60-90 DEG C, adding initiator, polyreaction 4-6 hour, centrifugal, and dialysis, obtains polymethacrylates PMEO
2mA microgel glue core solution, i.e. M glue core solution; Wherein MEO
2mA concentration is in the solution 20-25mmol/L;
(3) MEO is added in the M glue core solution obtained in step (2)
2mA, oligomeric ethylene glycol methyl ether methacrylate OEGMA, emulsifying agent and cross-linking agent, pass into nitrogen temperature to 60-90 DEG C, add initiator, polyreaction 6-8h, centrifugal, dialysis, forms P (MEO at M glue core skin
2mA-co-OEGMA) polymeric outer layer, i.e. MO shell, obtain polyethylene glycol methacrylate-styrene polymer MEO
2mA/EO
2mA-co-OEGMA nucleocapsid structure microgel, i.e. M/MO microgel; Wherein, MEO
2the amount of the monomeric substance of MA and OEGMA is than being 40-50:10-15, and the concentration of emulsifying agent is 1.5-1.8mmol/L, and the concentration of cross-linking agent is 0.5-0.6mmol/L;
(4) in the M/MO microgel solution described in step (3), copper sulphate pentahydrate stirring at normal temperature 3-5 hour is added; Add ammonium sulfide solution after being warming up to 60-90 DEG C, under stirring condition, carry out reaction 4-6 hour; Gained solution centrifugal is cleaned, can obtain nano-copper sulfide composite microgel material MEO
2mA/MEO
2mA-co-OEGMA-CuS, i.e. M/MO-CuS nano-complex; Wherein the mass ratio of copper sulphate pentahydrate and ammonium sulfide is 3:1-3.5:1; M/MO microgel solution is 10-30:1 with the amount of substance ratio of anhydrous cupric sulfate;
(5) doxorubicin hydrochloride DOX is dissolved in the phosphate buffered solution containing M/MO-CuS nano-complex, stirs 24-48 hour; Centrifugal, dialysis, obtains M/MO-CuS-DOX capsule of nano, i.e. MEO
2mA/MEO
2the photic hot microcapsule of the controlled response of MA-co-OEGMA-CuS-DOX; Wherein the mass ratio of DOX and nano-copper sulfide composite microgel material is 1:100-1:10; The amount of substance of DOX and M/MO-CuS nano-complex is than being 1:10-100.
3. a kind of near infrared light with thermotherapy/chemotherapy dual function according to claim 2 stimulates the preparation method of the photic hot microcapsule of controlled response, it is characterized in that, in described step (3), emulsifying agent is dodecylbenzene sodium sulfonate.
4. a kind of near infrared light with thermotherapy/chemotherapy dual function according to claim 2 stimulates the preparation method of the photic hot microcapsule of controlled response, it is characterized in that, in described step (3), cross-linking agent is polyethylene glycol dimethacrylate.
5. a kind of near infrared light with thermotherapy/chemotherapy dual function according to claim 2 stimulates the preparation method of the photic hot microcapsule of controlled response, it is characterized in that, MEO in described step (3)
2the concentration of MA is the concentration of 40-50mmol/L, OEGMA is 10-15mmol/L.
6. a kind of near infrared light with thermotherapy/chemotherapy dual function according to claim 2 stimulates the preparation method of the photic hot microcapsule of controlled response, it is characterized in that, described step (2) and the middle initiator of step (3) are potassium peroxydisulfate.
7. a kind of near infrared light with thermotherapy/chemotherapy dual function according to claim 2 stimulates the preparation method of the photic hot microcapsule of controlled response, it is characterized in that, the concentration of described step (2) and the middle initiator of step (3) is 0.5-0.7mmol/L.
8. a kind of near infrared light with thermotherapy/chemotherapy dual function according to claim 2 stimulates the preparation method of the photic hot microcapsule of controlled response, it is characterized in that, the speed stirred after adding ammonium sulfide solution in described step (4) is 300rpm.
9. a kind of near infrared light with thermotherapy/chemotherapy dual function according to claim 2 stimulates the preparation method of the photic hot microcapsule of controlled response, it is characterized in that, the speed stirred in described step (5) is 100rpm.
10. a kind of near infrared light with thermotherapy/chemotherapy dual function according to claim 2 stimulates the preparation method of the photic hot microcapsule of controlled response, it is characterized in that, the photic hot microcapsule of the controlled response obtained in described step (5) is applied near infrared light thermal therapeutical, the controllable release of medicine, the heat/chemotherapy of tumor.
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| CN114668853A (en) * | 2022-03-10 | 2022-06-28 | 东华大学 | Allicin-containing tumor in-situ response nanoparticle and preparation and application thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105963712A (en) * | 2016-06-29 | 2016-09-28 | 合肥工业大学 | Copper telluret nanometer compound medicine granules for thermal chemotherapy and method for constructing copper telluret nanometer compound medicine granules |
| CN108047462A (en) * | 2017-12-30 | 2018-05-18 | 广西师范大学 | Preparation method and applications based on poly- N-phenylglycine-polyethylene glycol hydrogel |
| CN108047462B (en) * | 2017-12-30 | 2020-12-29 | 广西师范大学 | Preparation method and application of hydrogel based on poly N-phenylglycine-polyethylene glycol |
| CN114668853A (en) * | 2022-03-10 | 2022-06-28 | 东华大学 | Allicin-containing tumor in-situ response nanoparticle and preparation and application thereof |
| CN114668853B (en) * | 2022-03-10 | 2023-08-04 | 东华大学 | Allicin-containing tumor in-situ response nanoparticle and preparation and application thereof |
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| CN105148271B (en) | 2018-06-26 |
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