CN110279651A - A kind of hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus - Google Patents
A kind of hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus Download PDFInfo
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Abstract
The hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus that the present invention provides a kind of, including agarose aquogel carrier and the black phosphorus nano flake and antitumor immune drug that are supported in the agarose aquogel carrier.The hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus is responded near infrared light, the transformation of gelatinized to collosol state can be realized by near infrared light, to realize that controllably immune drug discharges for part, effectively kill lesions position tumour cell, and have controlled degradation characteristic, there is high clinical value for the treatment of cancer.The preparation method for hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus that the present invention also provides this.
Description
Technical field
The present invention relates to Nano biomedical material technical fields, closely red more particularly to a kind of hydrogel based on black phosphorus
Outer smooth realizing controlled-release immune substance system and preparation method thereof.
Background technique
Cancer seriously endangers the life and health of the mankind, and at present be directed to cancer clinical treatment, either chemotherapy,
Operative treatment or radiotherapy all have very big side effect to body, and after pernicious transfer occurs, no matter using it is above-mentioned which kind of
Mode is all difficult to thoroughly cure.Although having a large amount of human and material resources, the research of cancer has been put into financial resources, progress ten
Dividing limited, cancer effectively treatment is still the very big test that the mankind face.
Some researches show that be applied to cancer diagnosis therapy field for large biological molecule and nanotechnology, before wide
Scape and clinical value.Wherein, the hydrogel immune drug carrier with light-operated release is a kind of novel Cancer Treatment Regimens, benefit
With laser irradiation controlled release immune drug, local is carried out to focal part to immune substance, the exciting light of irradiation is generally adopted
It is a kind of Cancer Treatment Regimens of Noninvasive near infrared light, can effectively penetrates human normal tissue and reach cancer location,
The damage of normal tissue is reduced to a great extent.However photosensitive nanoparticles (such as gold nano currently used for light-operated release
Grain) photothermal conversion efficiency is lower, non-degradable, bring difficulty to clinical application.
Recent studies have found that black phosphorus two-dimensional material is due to hypotoxicity, high-biocompatibility, high extinction coefficient and bloom
Thermal conversion efficiency has great application potential, therefore, it is necessary to open in terms of bio-medical field, especially treatment of cancer
It sends out that the hydrogel based on black phosphorus is light-operated a kind of and releases immune substance system, it is difficult to solve existing hydrogel immune drug carrier clinical application
The problem of.
Summary of the invention
In consideration of it, the present invention provides a kind of hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus, tool
There is near infrared light response, the transformation of gelatinized to collosol state can be realized by near infrared light, to realize local light
Controlled release immune substance effectively kills lesions position tumour cell, and at the same time having controlled degradation characteristic.
Specifically, in a first aspect, the present invention provides a kind of hydrogel near infrared light realizing controlled-release immune substance based on black phosphorus
System including agarose aquogel carrier and the black phosphorus nano flake being supported in the agarose aquogel carrier and resists
Cancer immune drug.
Near infrared light realizing controlled-release immune substance system provided by the invention is carried using agarose aquogel as immune drug controlled release
Body, using black phosphorus as photosensitizer, since black phosphorus has very high photothermal conversion efficiency, under the action of near infrared light,
Black phosphorus dissolves the agarose aquogel of gelatinized in collosol state, to realize antitumor immune drug for big calorimetric is generated
Controlled release, realize and locally give immune substance to lesions position, while black phosphorus is issued from high-intensitive near infrared light effect
Raw degradation, therefore the present invention releases immune substance system that the controlled degradation of immune drug carrier and photosensitizer can be achieved at the same time, to have
Hope the clinical efficacy for significantly improving treatment of cancer.
In the present invention, the collosol temperature of the agarose aquogel carrier is 40 DEG C -50 DEG C, and the immune substance system of releasing exists
40 DEG C the following are gelatinizeds, and are changed into collosol state at 40 DEG C -50 DEG C.Specifically, collosol temperature can be 40 DEG C, 42
℃,45℃,48℃,50℃.The lower agarose of collosol temperature is selected, on the one hand can to release immune substance system not close
It is gelatinized when infrared light action, antitumor immune drug and black phosphorus is held onto, improves the utilization of antitumor immune drug
Rate, while avoiding the injury of antitumor immune drug normal tissue cell；On the other hand it may make that releasing immune substance system is having closely
When infrared light action, the heat that can be generated by the photothermal conversion effect of black phosphorus nano flake dissolves, and realizes light-operated in vivo release
Immune substance.
Described to release in immune substance system in the present invention, the content of the black phosphorus nano flake is 0.01-1mg/mL, described
The mass content of antitumor immune drug is 0.01-1mg/mL.Further, the content of black phosphorus nano flake is 0.2-0.5mg/
ML, the mass content of the antitumor immune drug are 0.2-0.5mg/mL.The suitable black phosphorus nano flake content is conducive to
Improve the stability and realizing controlled-release immune substance ability of near infrared light realizing controlled-release immune substance system.The mass content of antitumor immune drug
Reasonable set can be carried out according to specific antitumor immune medicament categories and with immune dose demand.
In the present invention, the agarose aquogel carrier has agarose and water to constitute, in the agarose aquogel carrier
The mass content of agarose is 0.5%-2%, and further, the mass content of agarose is 0.8%-1.5% or 1.0%-
1.2%.The mass content of agarose directly affects the mesh size and mechanical strength of gel.
In the present invention, the length and width dimensions of the black phosphorus nano flake are 50nm-200nm；The thickness of the black phosphorus nano flake
Degree is 1nm-5nm.Optionally, the size of black phosphorus nano flake be 50nm-150nm, 100nm-150nm, 120nm-180nm,
160nm-200nm.Optionally, with a thickness of 1-3nm or 2-4nm.Suitable black phosphorus nano flake length and width dimensions and thickness are conducive to
Its evenly dispersed and to near-infrared radiation absorption in agarose aquogel.
Since black phosphorus nano flake surface has strong elecrtonegativity, the antitumor immune drug moiety is adsorbed on described black
Phosphorus nano flake surface, part independent dispersion is in the network structure that the agarose aquogel carrier is formed.
In the present invention, black phosphorus nano flake surface is coated with polyoxamide, the black phosphorus nano flake and poly- second
The mass ratio of glycol amine is 1: 0.5-2.Further, the mass ratio of the black phosphorus nano flake and polyoxamide is 1: 0.8-
1.5 or 1: 1-1.2.The polyoxamide includes methyl polyoxamide (CH3-PEG-NH2), methoxy poly (ethylene glycol) amine
(CH3O-PEG-NH2, referred to as mPEG-NH2) and polyethylene glycol diamines (NH2-PEG-NH2At least one of).The poly- second
Glycol amine is adsorbed on black phosphorus nano flake surface by electrostatic attraction, and the weight average molecular weight of the polyoxamide is
2000-30000.The biocompatibility of black phosphorus nano flake can be improved in polyoxamide, and black phosphorus nano flake is effectively avoided to send out
It is raw to assemble and improve the stability of black phosphorus nanometer sheet in aqueous solution, therefore can make black phosphorus nano flake is uniform and stable to be dispersed in institute
It states in hydrogel carrier, realizes and good light-operated release immune substance.
The antitumor immune drug includes the immune drug of currently used treating cancer, such as PD1 antibody.
The size of hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus of the invention can be according to practical application
Depending on environment, it is solid-state that volume can be clipped to a centimetre rank from micro/nano level at normal temperature, when carrying out internal injection, need to be added
Heat to making it be transformed into collosol state, it is to be implanted in vivo after be converted at a temperature of physiological environment and rapidly gelatinized, it is subsequent
Immune drug release is realized at collosol state by near infrared light role transformation again.
In the present invention, the black phosphorus nano flake and agarose all have good biocompatibility, can be dropped by biology
Solution or normal physiological pathway excrete, and have no toxic side effect to organism, biological safety height.
The hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus that first aspect present invention provides has close
Infrared light (700-1500nm) response, the photo-thermal for having both black phosphorus optothermal material kill the chemotherapeutic treatment of tumour and chemotherapeutic immunity drug
The effect of tumour, has high clinical value for treatment of cancer.
Second aspect, the system for the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus that the present invention provides a kind of
Preparation Method, comprising the following steps:
Black phosphorus nano flake is provided, the black phosphorus nano flake is distributed in water phase, obtains the dispersion of black phosphorus nano flake
Liquid；Antitumor immune drug is added into above-mentioned dispersion liquid, obtains mixed solution after mixing, the mixed solution is heated to
50-70 DEG C, agarose is added, hydrogel is formed after cooling and exempts to get to the hydrogel near infrared light realizing controlled-release based on black phosphorus
Epidemic disease medicine system.
In the present invention, the length and width dimensions of the black phosphorus nano flake are 50nm-200nm；The thickness of the black phosphorus nano flake
Degree is 1nm-5nm.Optionally, the size of black phosphorus nano flake be 50nm-150nm, 100nm-150nm, 120nm-180nm,
160nm-200nm.Optionally, with a thickness of 1-3nm or 2-4nm.The acquisition pattern of the black phosphorus nano flake is unlimited, such as can be with
It is using solution removing bonding probes ultrasonic method preparation, and centrifuge tube centrifugation to be used to collect, is pure using blocky black phosphorus as raw material
Change obtains, and the ultrasonic time of the probe sonication is 12-18 hours, and during the probe sonication, continual ultrasonic 45 seconds -1 is small
When, and -1 hour 15 seconds is waited as a cycle, power amplifier 20%-30%, the rate of the centrifugation is 1000rpm -
2000rpm, time are 6-15 minutes, and temperature is 4 DEG C.
In the present invention, the collosol temperature of the hydrogel formed after the agarose is cooling is 40 DEG C -50 DEG C, it is described release it is immune
The following are gelatinizeds at 40 DEG C for medicine system, and are changed into collosol state at 40 DEG C -50 DEG C.Specifically, collosol temperature can be
40℃、42℃、45℃、48℃、50℃。
Described to release in immune substance system in the present invention, the content of the black phosphorus nano flake is 0.01-1mg/mL, described
The mass content of antitumor immune drug is 0.01-1mg/mL.Further, the content of black phosphorus nano flake is 0.2-0.5mg/
ML, the mass content of the antitumor immune drug are 0.2-0.5mg/mL.
In the present invention, the mass content of agarose is 0.5%-2%, further, agar in the agarose aquogel
The mass content of sugar is 0.8%-1.5% or 1.0%-1.2%.
In the present invention, the antitumor immune drug includes the immune drug of currently used treating cancer, such as PD1 antibody.
It further comprise dispersing in the black phosphorus nano flake before the antitumor immune drug is added in the present invention
Polyoxamide is added in liquid, obtains the black phosphorus of polyoxamide cladding under stirring or under the action of combination of ultrasound stirring
Nano flake.The revolving speed of the stirring is 800rpm-1200rpm, and the duration is 2-4 hours.The frequency of the ultrasound is
3000-4500HZ, duration are 0.5-2 hours.The ultrasound and stirring can be and successively carry out, such as can be first ultrasound
It 0.5 hour, is stirred for 3 hours.The polyoxamide includes methyl polyoxamide (CH3-PEG-NH2), the poly- second two of methoxyl group
Hydramine (CH3O-PEG-NH2, referred to as mPEG-NH2) and polyethylene glycol diamines (NH2-PEG-NH2At least one of).It is described
The weight average molecular weight of polyoxamide is 2000-30000.
The preparation side for the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus that second aspect of the present invention provides
Method, preparation process is simple to operation, is suitable for industrialized production.
Detailed description of the invention
Fig. 1 is the knot of the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus prepared by the embodiment of the present invention 1
Structure schematic diagram；
Fig. 2 is the structural representation of the black phosphorus nano flake for the polyoxamide cladding being prepared in the embodiment of the present invention 1
Figure；
Fig. 3 is the EDS of the black phosphorus nano flake for the polyoxamide cladding being prepared in the embodiment of the present invention 1
(Energy Dispersive Spectrometer, power spectrum) figure；
Fig. 4 is that the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus of the embodiment of the present invention releases immune substance
With degradation schematic diagram；
Fig. 5 is that the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus prepared by the embodiment of the present invention 1 exists
Cell in vitro fluorescence imaging in Hela cell, under illumination different time；
Fig. 6 is that the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus of the embodiment of the present invention varies with temperature
Immune drug release profiles；
Fig. 7 is the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus of the preparation of the embodiment of the present invention 1 not
Cytotoxicity result in same cancer cell (Hela, MCF-7, A549 and PC3)；
Fig. 8 is the result figure that the cell activity under the effect of different gel rubber systems changes over time.
Specific embodiment
As described below is the preferred embodiment of the embodiment of the present invention, it is noted that for the common skill of the art
For art personnel, without departing from the principles of the embodiments of the present invention, several improvements and modifications can also be made, these improvement
Also it is considered as the protection scope of the embodiment of the present invention with retouching.
Embodiment 1
A kind of preparation method of the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus, comprising the following steps:
(1) black phosphorus nano flake is prepared using solution removing bonding probes ultrasonic method: takes 50mg bulk black phosphorus material, is placed in
In 100mL ultrapure water, probe sonication is carried out, the ultrasonic time of the probe sonication method is 12 hours, and process is continual ultrasonic 45
Second, waiting 15 seconds is a cycle, power amplifier 20%；After ultrasound, brownish black stripper is taken to be placed in centrifuge tube,
1000rpm is centrifuged 10 minutes, and temperature is 4 DEG C, precipitates the blocky black phosphorus being not peeled off, and the blocky black phosphorus of careful separation precipitating and
Black phosphorus nano flake in supernatant, with further purification & isolation black phosphorus nano flake；
(2) above-mentioned gained black phosphorus nano flake is distributed in water, successively by the way of ultrasound and magnetic agitation, black
The surface of phosphorus nano flake coats polyoxamide, obtain include the black phosphorus nano flake of polyoxamide cladding solution；
Wherein the mass ratio of black phosphorus nano flake and polyoxamide is 1:2, and ultrasonic frequency is 4000HZ, and the duration is 2 hours,
Magnetic agitation rotating speed is 800rpm, and the duration is 4 hours；The polyoxamide is methyl polyoxamide, methoxyl group is poly-
At least one of ethylene glycol amine and polyethylene glycol diamines, the weight average molecular weight of polyoxamide are 2000-30000；
It (3) include that antitumor immune medicine is added in the solution for the black phosphorus nano flake that polyoxamide coats to above-mentioned gained
Object PD1 antibody, obtains mixed solution；
(4) mixed solution is heated to 50 DEG C, then the agarose that collosol temperature is 40 DEG C is added thereto, to agar
Sugar is completely dissolved, and hydrogel is formed after cooling to get the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus of arriving.
Fig. 1 is the knot of the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus prepared by the embodiment of the present invention 1
Structure schematic diagram, including agarose aquogel carrier 10, the black phosphorus nanometer being evenly distributed in the agarose aquogel carrier 10
Thin slice 20 and antitumor immune drug 30.The hydrogel near infrared light realizing controlled-release immune substance based on black phosphorus that the present embodiment is prepared
System, the mass concentration of black phosphorus nano flake are 500ppm, and the mass concentration of agarose is 1% in agarose aquogel carrier.
Fig. 2 and Fig. 3 is respectively that the black phosphorus for the polyoxamide cladding that step (2) is prepared in the embodiment of the present invention 1 is received
The structural schematic diagram and EDS energy spectrum diagram of rice thin slice；21 be black phosphorus nano flake in figure, and 22 be polyoxamide.From Fig. 3 C, O,
The peak position of N, which can be known, has coated polyoxamide on black phosphorus.
The hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus that the embodiment of the present invention is prepared can be realized
Part is carried out to immune substance to lesions position, to after the completion of immune substance, by 808nm near infrared band laser excitation, black phosphorus is received
Rice thin slice will play its superpower photothermal conversion performance, provides the agarose hydrogel gum softening that amount of heat makes gelling state, mentions
Diffusion coefficient of the high anticancer immune drug in hydrogel, thus quick release immune drug；Then laser function is further increased
Rate, for example it is increased to 2W from the 1W of beginning, hydrogel is dissolved, its degradation is accelerated, and accelerates internal black phosphorus nano flake
Degradation, thus realize the controlled release of antitumor immune drug, it is final effectively to kill lesions position cancer cell.Fig. 4 is that the present invention is real
That applies the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus of example preparation releases immune substance and degradation schematic diagram.
In Fig. 5, the hydrogel near infrared light based on black phosphorus for a), b), c), d) being respectively the preparation of the embodiment of the present invention 1 can
Cell in vitro fluorescence imaging of the controlled release immune substance system in Hela cell, under illumination different time.0min, 5min from figure,
The different light application time results of 10min, 15min can be seen that the increase with light application time, and the PD1 antibody released is more,
The quantity of normal cancer cell is constantly reduced, after illumination 15min, the substantially all death of cancer cell.
Fig. 6 is that the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus of the embodiment of the present invention 1 becomes with temperature
The immune drug release profiles of change.Curve 1 represents temperature curve in figure, and curve 2 represents the immune drug being discharged into solution
Concentration, on indicate heating, and off indicates to stop heating.Result can see from figure, and each heat temperature raising can all lead to immune substance
Object quickly releases, and when stopping heating, immune drug rate of release is very low.
Embodiment 2
A kind of preparation method of the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus, comprising the following steps:
(1) black phosphorus nano flake is prepared using solution removing bonding probes ultrasonic method: takes 50mg bulk black phosphorus material, is placed in
In 100mL ultrapure water, probe sonication is carried out, the ultrasonic time of the probe sonication method is 18 hours, and process is continual ultrasonic 1
Hour, waiting 1 hour is a cycle, power amplifier 20%.After ultrasound, brownish black stripper is taken to be placed in centrifuge tube,
2000rpm is centrifuged 6 minutes, and temperature is 4 DEG C, precipitates the blocky black phosphorus being not peeled off, and the blocky black phosphorus of careful separation precipitating and
Black phosphorus nano flake in supernatant, with further purification & isolation black phosphorus nano flake；
(2) above-mentioned gained black phosphorus nano flake is distributed in water, successively by the way of ultrasound and magnetic agitation, black
The surface of phosphorus nano flake coats polyoxamide, obtain include the black phosphorus nano flake of polyoxamide cladding solution；
Wherein the mass ratio of black phosphorus nano flake and polyoxamide is 1:1, and ultrasonic frequency is 3500HZ, and the duration is 0.5 small
When, magnetic agitation rotating speed 1000rpm, the duration is 4 hours；The polyoxamide is methyl polyoxamide, methoxy
At least one of base polyoxamide and polyethylene glycol diamines, the weight average molecular weight of polyoxamide are 2000-30000；
It (3) include that antitumor immune medicine is added in the solution for the black phosphorus nano flake that polyoxamide coats to above-mentioned gained
Object PD1 antibody, obtains mixed solution；
(4) mixed solution is heated to 60 DEG C, then the agarose that collosol temperature is 45 DEG C is added thereto, to agar
Sugar is completely dissolved, and hydrogel is formed after cooling to get the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus of arriving.This
The hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus that embodiment is prepared, the quality of black phosphorus nano flake are dense
Degree is 1000ppm, and the mass concentration of agarose is 0.5% in agarose aquogel carrier.
Embodiment 3
A kind of preparation method of the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus, comprising the following steps:
(1) black phosphorus nano flake is prepared using solution removing bonding probes ultrasonic method, takes 50mg bulk black phosphorus material, is placed in
In 100mL ultrapure water, probe sonication is carried out, the ultrasonic time of the probe sonication method is 16 hours, and process is continual ultrasonic 1
Hour, waiting 1 hour is a cycle, power amplifier 25%.After ultrasound, brownish black stripper is taken to be placed in centrifuge tube,
1000rpm is centrifuged 15 minutes, and temperature is 4 DEG C, precipitates the blocky black phosphorus being not peeled off, and the blocky black phosphorus of careful separation precipitating and
Black phosphorus nano flake in supernatant, with further purification & isolation black phosphorus nano flake；
(2) above-mentioned gained black phosphorus nano flake is distributed in water, successively by the way of ultrasound and magnetic agitation, black
The surface of phosphorus nano flake coats polyoxamide, obtain include the black phosphorus nano flake of polyoxamide cladding solution；
Wherein the mass ratio of black phosphorus nano flake and polyoxamide is 1:0.5, and ultrasonic frequency is 4000HZ, and the duration is 1 small
When, magnetic agitation rotating speed 1200rpm, the duration is 4 hours；The polyoxamide is methyl polyoxamide, methoxy
At least one of base polyoxamide and polyethylene glycol diamines, the weight average molecular weight of polyoxamide are 2000-30000；
It (3) include that antitumor immune medicine is added in the solution for the black phosphorus nano flake that polyoxamide coats to above-mentioned gained
Object PD1 antibody, obtains mixed solution；
(4) mixed solution is heated to 70 DEG C, then the agarose that collosol temperature is 50 DEG C is added thereto, to agar
Sugar is completely dissolved, and hydrogel is formed after cooling to get the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus of arriving.This
The hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus that embodiment is prepared, the quality of black phosphorus nano flake are dense
Degree is 200ppm, and the mass concentration of agarose is 2% in agarose aquogel carrier.
Embodiment 4
A kind of preparation method of the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus, comprising the following steps:
(1) black phosphorus nano flake is prepared using solution removing bonding probes ultrasonic method, takes 50mg bulk black phosphorus material, is placed in
In 100mL ultrapure water, probe sonication is carried out, the ultrasonic time of the probe sonication method is 14 hours, and process is continual ultrasonic
0.5 hour, waiting 0.5 hour was a cycle, power amplifier 30%.After ultrasound, brownish black stripper is taken to be placed in centrifuge tube
In, 2000rpm is centrifuged 10 minutes, and temperature is 4 DEG C, precipitates the blocky black phosphorus being not peeled off, and the bulk of careful separation precipitating is black
Black phosphorus nano flake in phosphorus and supernatant, with further purification & isolation black phosphorus nano flake；
(2) above-mentioned gained black phosphorus nano flake is distributed in water, successively by the way of ultrasound and magnetic agitation, black
The surface of phosphorus nano flake coats polyoxamide, obtain include the black phosphorus nano flake of polyoxamide cladding solution；
Wherein the mass ratio of black phosphorus nano flake and polyoxamide is 1:1, and ultrasonic frequency is 4500HZ, and the duration is 1.5 small
When, magnetic agitation rotating speed 1000rpm, the duration is 3 hours；The polyoxamide is methyl polyoxamide, methoxy
At least one of base polyoxamide and polyethylene glycol diamines, the weight average molecular weight of polyoxamide are 2000-30000；
It (3) include that antitumor immune medicine is added in the solution for the black phosphorus nano flake that polyoxamide coats to above-mentioned gained
Object PD1 antibody, obtains mixed solution；
(4) mixed solution is heated to 55 DEG C, then the agarose that collosol temperature is 45 DEG C is added thereto, to agar
Sugar is completely dissolved, and hydrogel is formed after cooling to get the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus of arriving.This
The hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus that embodiment is prepared, the quality of black phosphorus nano flake are dense
Degree is 50ppm, and the mass concentration of agarose is 1.5% in agarose aquogel carrier.
Fig. 7 is that the hydrogel near infrared light realizing controlled-release based on black phosphorus of the different black phosphorus concentration of preparation of the embodiment of the present invention is exempted from
Toxicity data of the epidemic disease medicine system in various cancers cell (A549, Hela, PC3 and MCF-7)；Four groups of difference black phosphorus are shared in figure
The experiment of concentration (0ppm, 50ppm, 200ppm, 500ppm), in every group of experiment, from left to right each pillar be successively denoted as 1,2,
3,4, it represents Hela wherein 1 represents A549,2,3 represent PC3,4 represent MCF-7.It can be seen from the figure that the embodiment of the present invention
The hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus do not have cytotoxicity in no laser irradiation, it is raw
Object safety is good, has no toxic side effect.
Fig. 8 is the result figure that the cell activity under the effect of different gel rubber systems changes over time.Wherein ordinate represents thin
Cytoactive, 100% indicates cell activity highest, and 0 indicates cell whole apoptosis；Abscissa represents cell and is made by different gel rubber systems
Time specifically shows four groups of experimental results that action time is respectively 0min, 5min, 10min, 15min in figure, often
In group result, each pillar is successively denoted as 1,2,3,4 from left to right, wherein the case where 1 representative is only with laser irradiation；2 represent
The hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus of the embodiment of the present invention 1 is added, but not laser irradiation
Situation；The case where hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus of the embodiment of the present invention 1 is added in 3 representatives
(black phosphorus concentration is 500ppm, 1%) agarose mass content is；4 represent the water-setting based on black phosphorus that the embodiment of the present invention 2 is added
The case where glue near infrared light realizing controlled-release immune substance system, (black phosphorus concentration was 1000ppm, 0.5%) agarose mass content is.
It should be noted that according to the above description the announcement of book and with illustrate, those skilled in the art in the invention also
It can change and modify the above embodiment.Therefore, the invention is not limited to specific realities disclosed and described above
Mode is applied, some equivalent modifications of the invention and change should also be as within scope of protection of the claims of the invention.This
Outside, although using some specific terms in this specification, these terms are merely for convenience of description, not to the present invention
Constitute any restrictions.
Claims (11)
1. a kind of hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus, which is characterized in that including agarose hydrogel
Glue carrier and the black phosphorus nano flake and antitumor immune drug being supported in the agarose aquogel carrier.
2. the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus as described in claim 1, which is characterized in that institute
The collosol temperature for stating agarose aquogel carrier is 40 DEG C -50 DEG C, described to release immune substance system at 40 DEG C the following are gelatinized,
And it is changed into collosol state at 40 DEG C -50 DEG C.
3. the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus as described in claim 1, which is characterized in that institute
It states and releases in immune substance system, the content of the black phosphorus nano flake is 0.01-1mg/mL, and the quality of the antitumor immune drug contains
Amount is 0.01-1mg/mL.
4. the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus as described in claim 1, which is characterized in that institute
The mass content for stating agarose in agarose aquogel carrier is 0.5%-2%.
5. the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus as described in claim 1, which is characterized in that institute
The length and width dimensions for stating black phosphorus nano flake are 50nm-200nm；The black phosphorus nano flake with a thickness of 1nm-5nm.
6. the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus as described in claim 1, which is characterized in that institute
It states antitumor immune drug moiety and is adsorbed on black phosphorus nano flake surface, part independent dispersion is carried in the agarose aquogel
In the network structure that body is formed.
7. the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus as described in claim 1, which is characterized in that institute
It states black phosphorus nano flake surface and is coated with polyoxamide, the mass ratio of the black phosphorus nano flake and polyoxamide is 1:
0.5-2。
8. the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus as claimed in claim 7, which is characterized in that institute
It states polyoxamide and black phosphorus nano flake surface is adsorbed on by electrostatic attraction, the polyoxamide includes the poly- second of methyl
At least one of glycol amine, methoxy poly (ethylene glycol) amine and polyethylene glycol diamines, the weight average molecular weight of the polyoxamide
For 2000-30000.
9. the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus as described in claim 1, which is characterized in that institute
Stating antitumor immune drug includes PD1 antibody.
10. a kind of preparation method of the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus, which is characterized in that including
Following steps:
Black phosphorus nano flake is provided, the black phosphorus nano flake is distributed in water phase, black phosphorus nano flake dispersion liquid is obtained；To
Antitumor immune drug is added in above-mentioned dispersion liquid, obtains mixed solution after mixing, the mixed solution is heated to 50-70
DEG C, agarose is added, forms hydrogel after cooling to get the hydrogel near infrared light realizing controlled-release immune substance system based on black phosphorus is arrived
System.
11. preparation method as claimed in claim 10, which is characterized in that before the antitumor immune drug is added, into one
Step, which is included in the black phosphorus nano flake dispersion liquid, is added polyoxamide, obtains polyoxamide cladding under stirring
Black phosphorus nano flake.
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Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110801429A (en) * | 2019-10-25 | 2020-02-18 | 深圳大学 | Drug release fiber tube, preparation method thereof, drug controlled release stent and application |
| CN111330007A (en) * | 2020-03-17 | 2020-06-26 | 深圳罗兹曼国际转化医学研究院 | Composition for enhancing anti-tumor immune response and application thereof |
| CN111939119A (en) * | 2020-09-01 | 2020-11-17 | 深圳瀚光科技有限公司 | Nano drug delivery system based on black phosphorus hydrogel and preparation method and application thereof |
| CN112220758A (en) * | 2020-10-16 | 2021-01-15 | 温州医科大学附属第二医院（温州医科大学附属育英儿童医院） | Preparation of meltable hydrogel drug-loaded microspheres with photo-thermal responsiveness and application of microspheres in cell amplification |
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| CN113198042A (en) * | 2021-04-25 | 2021-08-03 | 华南理工大学 | Growth factor loaded injectable nanocomposite hydrogel material and construction method and application thereof |
| WO2022021508A1 (en) * | 2020-07-28 | 2022-02-03 | 清华大学 | Method and system for using pulsed laser to control drug release |
| CN114712498A (en) * | 2020-12-21 | 2022-07-08 | 苏州北科纳米科技有限公司 | Light-operated slow-release injection for triggering anti-tumor immune response and preparation method thereof |
| CN114796491A (en) * | 2022-04-27 | 2022-07-29 | 中国药科大学 | Antibody-modified anti-tumor targeted drug delivery and combined treatment system and preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107496444A (en) * | 2017-08-29 | 2017-12-22 | 深圳大学 | A kind of selenium doping black phosphorus prodrug and preparation method thereof |
| CN107854689A (en) * | 2017-11-27 | 2018-03-30 | 南京大学 | Activated form nano-probe and its biologic applications |
| CN107961213A (en) * | 2017-12-11 | 2018-04-27 | 张晗 | A kind of controllable medicine-releasing system of hydrogel near infrared light based on black phosphorus and preparation method thereof |
-
2019
- 2019-05-31 CN CN201910473466.6A patent/CN110279651A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107496444A (en) * | 2017-08-29 | 2017-12-22 | 深圳大学 | A kind of selenium doping black phosphorus prodrug and preparation method thereof |
| CN107854689A (en) * | 2017-11-27 | 2018-03-30 | 南京大学 | Activated form nano-probe and its biologic applications |
| CN107961213A (en) * | 2017-12-11 | 2018-04-27 | 张晗 | A kind of controllable medicine-releasing system of hydrogel near infrared light based on black phosphorus and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| 《医用药理学》编写组: "《医用药理学 第2版》", 30 September 1982, 人民卫生出版社 * |
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| CN110801429B (en) * | 2019-10-25 | 2023-04-07 | 深圳大学 | Drug release fiber tube, preparation method thereof, drug controlled release stent and application |
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| WO2022021508A1 (en) * | 2020-07-28 | 2022-02-03 | 清华大学 | Method and system for using pulsed laser to control drug release |
| CN111939119A (en) * | 2020-09-01 | 2020-11-17 | 深圳瀚光科技有限公司 | Nano drug delivery system based on black phosphorus hydrogel and preparation method and application thereof |
| CN112220758A (en) * | 2020-10-16 | 2021-01-15 | 温州医科大学附属第二医院（温州医科大学附属育英儿童医院） | Preparation of meltable hydrogel drug-loaded microspheres with photo-thermal responsiveness and application of microspheres in cell amplification |
| CN114712498A (en) * | 2020-12-21 | 2022-07-08 | 苏州北科纳米科技有限公司 | Light-operated slow-release injection for triggering anti-tumor immune response and preparation method thereof |
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| CN114796491A (en) * | 2022-04-27 | 2022-07-29 | 中国药科大学 | Antibody-modified anti-tumor targeted drug delivery and combined treatment system and preparation method and application thereof |
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