CN111558040B - High-molecular self-healing gel integrating magnetic resonance imaging and photothermal therapy and preparation and application thereof - Google Patents
High-molecular self-healing gel integrating magnetic resonance imaging and photothermal therapy and preparation and application thereof Download PDFInfo
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Abstract
The invention discloses a preparation method and application of a high-molecular self-healing gel integrating magnetic resonance imaging and photothermal therapy. The invention relates to Mn with biological activity2+As a chelating site, the hydrogel forms a three-dimensional network structure with natural polymers, and is doped with a nano gold rod with a photo-thermal effect, so that a safe and degradable medical hydrogel which can promote cell growth and repair of damaged tissues and has magnetic resonance imaging diagnosis and photo-thermal treatment is developed, and double effects of diagnosis and treatment can be met by one-time injection. Meanwhile, the composite hydrogel has considerable development prospect and potential medical value in the fields of tissue engineering, lesion diagnosis, fixed-point monitoring and imaging, photothermal therapy and the like by combining the self-healing function.
Description
Technical Field
The invention belongs to the field of medical polymer materials, and particularly relates to a polymer self-healing gel integrating magnetic resonance imaging and photothermal therapy, and preparation and application thereof.
Background
Magnetic resonance imaging is an emission tomography, which obtains electromagnetic signals from a human body by using a magnetic resonance phenomenon so as to reconstruct a digital image of a human body system, and is widely used in the medical imaging aspect of injuries and lesions of spinal cords, craniocerebra, joints and the like at present, and particularly has remarkable effect in diagnosing spinal cavities, cranial neuropathy, brain tumors, angiography, soft tissue injuries and the like.
At present, most of traditional magnetic resonance contrast agents are heavy metal complexes or nano oxides, and although the contrast agents have good contrast effect and are applied to clinical treatment, various defects still exist, such as common heavy metal complex Gd3+The toxicity is high, and even the brain allergy and the nerve cell death can be caused; the commonly used nano Fe3O4The particles are small, flow with blood in the body, and are difficult to be discharged from the human metabolic system. In addition, the contrast agent is mostly injected in the form of solution, and has strong fluidity, short imaging time and unobvious effect. Therefore, in order to overcome the defects of high toxicity, difficult degradation and short diagnosis time of the traditional magnetic resonance contrast agent, a safe and degradable magnetic resonance imaging medical material with long imaging time needs to be developed.
The hydrogel prepared from the natural chitosan and the derivatives thereof becomes a good medical carrier material due to the advantages of high safety, strong plasticity, good biocompatibility and flexibility, easy degradation and the like. Recent studies have shown that Mn2+Can be used as a manganese-enhanced magnetic resonance diagnostic agent, can enhance longitudinal relaxation imaging signals, and replaces the traditional high-toxicity contrast agent. In addition, manganese also has certain biological activity and can promote cartilage formation. Gold nano-materials have been generally proved to be a more common photo-thermal reagent due to the plasma resonance characteristic.
Therefore, the present invention uses Mn2+Combined with nano Au to develop a medical hydrogel integrating magnetic resonance imaging and photothermal therapy, and simultaneously combined with the self-healing function of the hydrogel, the hydrogel can be used for tissue engineering, pathological change diagnosis, fixed-point monitoring and fixed-point monitoringThe imaging and photothermal therapy fields have great development prospect and potential medical value.
Disclosure of Invention
In order to overcome the defects and shortcomings in the prior art, the invention aims to provide a preparation method of a high-molecular self-healing gel integrating magnetic resonance imaging and photothermal therapy. Taking chitosan derivative from natural sources as a carrier substrate, adding gold nano material, and introducing Mn2+And (4) crosslinking the system to prepare the self-healing hydrogel composite material. The photothermal therapy of Au and the magnetic resonance imaging function of Mn are integrated, and the medical composite hydrogel dual diagnosis and treatment means is provided.
The invention also aims to provide the high-molecular self-healing gel which integrates the magnetic resonance imaging and the photothermal therapy.
The invention further aims to provide application of the high-molecular self-healing gel integrating magnetic resonance imaging and photothermal therapy.
The purpose of the invention is realized by the following technical scheme:
a preparation method of a high-molecular self-healing gel integrating magnetic resonance imaging and photothermal therapy comprises the following steps:
(1) adding p-aldehyde benzoic acid, 4-Dimethylaminopyridine (DMAP) and Dicyclohexylcarbodiimide (DCC) into the chitosan solution, stirring for 5-30 min, reacting for 1-4 days, precipitating, washing, and performing suction filtration to obtain aldehyde chitosan (OCS);
(2) at 25-40 ℃ to HAuCl4Adding a surfactant into the solution, stirring for 5-60 s, and adding NaBH4Stirring the solution for 5-60 s to obtain Au seed solution;
(3) at 25-40 ℃ to HAuCl4Adding a surfactant into the solution, stirring for 5-60 s, and adding AgNO3Stirring the solution for 5-60 s, adding a reducing agent solution, and stirring for 5-60 s to obtain a nano Au growth solution;
(4) adding the nano Au growth solution into the Au seed solution, stirring for 5-60 s at 25-40 ℃, standing for 6-18 h at normal temperature, centrifuging after the gold rod grows stably, washing, and performing suction filtration to obtain nano Au rod powder;
(5) dissolving aldehyde chitosan (OCS) in water, uniformly dispersing, adding nano Au bar powder, and stirring for 1-3 h to obtain a nano Au bar mixed solution;
(6) adding a nano Au bar mixed solution into a carboxymethyl chitosan solution, stirring for 2-5 h, and adding MnCl2·4H2And stirring the O aqueous solution for 4-20 hours to obtain the high-molecular self-healing composite hydrogel.
Preferably, the concentration of the chitosan solution in the step (1) is 1-5 wt% (w/w), the molecular weight of chitosan in the chitosan solution is 800-1000, the degree of deacetylation is 75-85%, and the solvent is at least one of dimethyl sulfoxide, acetone, methanol, ethanol and water.
Preferably, the mass ratio of the chitosan to the p-aldehyde benzoic acid, the 4-dimethylaminopyridine and the dicyclohexylcarbodiimide in the chitosan solution in the step (1) is (5-25): (20-60): (0.6-1.2): (10-35).
Preferably, the p-aldehyde benzoic acid in the step (1) is added in the form of a p-aldehyde benzoic acid solution, and the concentration of the p-aldehyde benzoic acid solution is 10-30 wt% (w/w); the 4-dimethylaminopyridine is added in the form of a 4-dimethylaminopyridine solution, and the concentration of the 4-dimethylaminopyridine solution is 0.6-1.2 wt% (w/w); the dicyclohexylcarbodiimide is added in the form of a dicyclohexylcarbodiimide solution, and the concentration of the dicyclohexylcarbodiimide solution is 10-35 wt% (w/w); the solvents of the p-formaldehyde benzoic acid solution, the 4-dimethylaminopyridine solution and the dicyclohexylcarbodiimide solution are the same as those of the chitosan solution.
Preferably, the stirring and the reaction of step (1) are both carried out at room temperature.
Preferably, the precipitation time in the step (1) is 12-48 h, the precipitating agent is deionized water, and the volume ratio of the reaction product mixed solution to the added precipitating agent is 9: (3-7); the washing is to repeatedly wash the solution for 5-10 times by using absolute ethyl alcohol and deionized water until the solution is colorless; the suction filtration is normal temperature and normal pressure suction filtration.
Preferably, the HAuCl of steps (2) and (3)4The concentration of the solution is 0.5-5 mmol/L, and the solvent is water.
Preferably, the step (A)2) The HAuCl4HAuCl in solution4Surfactants and NaBH4NaBH in solution4The molar ratio of (5-9) mmol: (1.25-50) mol: (5-12) mmol.
Preferably, the surfactant in steps (2) and (3) is Cetyl Trimethyl Ammonium Bromide (CTAB), the surfactant is added in the form of surfactant solution, the concentration of the surfactant solution is 0.05-2 mol/L, and the solvent is water.
Preferably, the NaBH of step (2)4The concentration of the solution is 5-12 mmol/L, and the solvent is water.
Preferably, the HAuCl of step (3)4HAuCl in solution4Surfactant, AgNO3AgNO in solution3And the molar ratio of the reducing agent in the reducing agent solution is (10-15) mmol: (1.25-50) mol: (4.2-10.8) mmol: (80-150) mmol.
Preferably, the reducing agent in the reducing agent solution in the step (3) is vitamin C (Vc) and NaBH4At least one of; the concentration is 80-150 mmol/L.
Preferably, the AgNO of step (3)3The concentration of the solution is 7-18 mmol/L, and the solvent is water.
Preferably, the volume ratio of the nano Au growth solution to the Au seed solution in the step (4) is (1-5): 1.
preferably, the rotating speed of the centrifugation in the step (4) is 5000-8000 r/min, and the time is 10-20 min; the washing is to repeatedly wash the solution for 5-10 times by using absolute ethyl alcohol and deionized water until the solution is colorless; the suction filtration is normal temperature and normal pressure suction filtration.
Preferably, the concentration of the solution formed by dissolving the aldehyde chitosan in the step (5) in water is 2-7 wt%.
Preferably, the mass ratio of the aldehyde chitosan in the step (5) to the nano Au bar powder is (2-7): (1-10).
Preferably, the concentration of the nano Au bar powder in the step (5) in the system is 1-10 wt%.
Preferably, the uniform dispersion in the step (5) is ultrasonic oscillation, and the ultrasonic time is 5-10 min.
Preferably, the concentration of the carboxymethyl chitosan solution in the step (6) is 2-8 wt%, wherein the molecular weight of the carboxymethyl chitosan is 2000, the substitution degree is 80-85%, and the solvent is water.
Preferably, the carboxymethyl chitosan in the carboxymethyl chitosan solution of step (6), the nano Au bars and the MnCl in the mixed solution of the nano Au bars2·4H2MnCl in aqueous O solution2·4H2The mass ratio of O is (20-80): (1-10): (2-16).
Preferably, the MnCl of the step (6)2·4H2The concentration of the O aqueous solution is 1-8 wt%.
The high-molecular self-healing gel prepared by the method integrates magnetic resonance imaging and photothermal therapy.
The application of the high-molecular self-healing gel integrates magnetic resonance imaging and photothermal therapy.
The aldehyde chitosan (OCS) in the raw materials used in the invention can stably wrap the nano gold rod, and the amino group on the carboxymethyl chitosan (CMC) molecular chain and the aldehyde group on the OCS molecular chain can generate Schiff base action, and simultaneously, the macromolecule physical winding and hydrogen bond action exist, so that a first layer of cross-linked network is formed. In addition, the amino and carboxyl groups on the molecular chain of CMC are mixed with Mn2+Coordination chelation exists between the two layers, and a second layer of cross-linked network is formed. The formation of a double-layer polymer cross-linked network greatly stabilizes the internal structure of the hydrogel; the nano gold rod has certain photo-thermal effect and chelated active substance Mn2+The magnetic resonance imaging material has the characteristics of manganese enhancement and magnetic resonance imaging; the composite medical hydrogel with good stability, high safety and two diagnosis and treatment means can be finally prepared.
The self-healing hydrogel with a three-dimensional network structure is formed by taking chitosan derivatives as main macromolecular chains, cooperating with the dynamic covalent bond formed by Schiff base bonds and the non-covalent bond formed by hydrogen bonds and metal coordination bonds and combining with the physical winding effect among the macromolecular chains, and meanwhile, nano gold rods are taken as nano fillers to be uniformly dispersed in the hydrogel network, so that not only are the rigid sites increased, but also the internal structure of the hydrogel is stabilized; and also hasCertain photo-thermal effect. Recombination of chelated active substance Mn2+The magnetic resonance imaging system can promote the repair of damaged nerves and has the characteristic of manganese-enhanced magnetic resonance imaging.
Compared with the prior art, the invention has the following advantages and beneficial effects:
1. the polymer gel provided by the invention is simple to prepare and high in safety. The gel can be prepared by mixing and stirring the raw materials in one pot at normal temperature without an initiator. In addition, compared with artificially synthesized macromolecules, the chitosan derivative is prepared from chitosan derivatives of natural sources, is degradable, biocompatible and higher in safety, and is more suitable for human medical treatment.
2. The polymer gel provided by the invention provides a new entry point for searching a substitute of a magnetic resonance imaging contrast agent. The traditional contrast agent has high toxicity, unstable in vivo flow and difficult degradation, and the natural polymer hydrogel has a three-dimensional network structure and is a good medical carrier; while a low concentration of Mn2+But also is a trace element required by human bodies, has certain biological activity and can promote the repair of damaged cartilage; therefore, the chelated Mn prepared by the invention2+The hydrogel has biological functions of promoting cell growth, repairing tissue and the like, and is expected to replace the existing high-toxicity contrast medium to be applied to human bodies.
3. The polymer gel provided by the invention provides a more convenient dual diagnosis and treatment means. Mn has been demonstrated to have manganese-enhanced magnetic resonance imaging properties and can be used as a contrast diagnostic agent; meanwhile, the system also comprises a nano gold rod, and can be applied to photo-thermal treatment; therefore, the composite hydrogel prepared by the invention can integrate magnetic resonance imaging and photothermal therapy, can meet the diagnosis and treatment effects by one-time injection, and provides a more accurate and convenient method for medical diagnosis and treatment.
4. The invention develops a research idea of combining multiple functions of magnetic resonance imaging plus, and although only relates to the research of the aspects of magnetic resonance imaging plus photothermal therapy, aiming at different functional requirements, the oriented preparation of the multifunctional composite material can be realized by adding raw materials with different characteristics, such as conductive materials, photothermal materials, imaging materials and the like, so that the aim of integrating multiple effects is fulfilled.
Drawings
Fig. 1 is a Scanning Electron Microscope (SEM) image of the composite hydrogel prepared in example 1 after lyophilization.
Fig. 2 is a swelling curve of the composite hydrogel prepared in example 2 at 37 ℃ in PBS buffer at pH 7.4.
Fig. 3 is a degradation curve of the composite hydrogel prepared in example 2 at 37 ℃ in PBS buffer at pH 7.4.
FIG. 4 is a graph showing the in vitro cytotoxic effect of the composite hydrogel prepared in example 5.
Detailed Description
The present invention will be described in further detail with reference to examples and drawings, but the embodiments of the present invention are not limited thereto.
Those who do not specify specific conditions in the examples of the present invention follow conventional conditions or conditions recommended by the manufacturer. The raw materials, reagents and the like which are not indicated for manufacturers are all conventional products which can be obtained by commercial purchase.
Example 1
(1) Weighing 2g carboxymethyl chitosan powder, dissolving in 100mL deionized water, magnetically stirring at normal temperature for 1h until the carboxymethyl chitosan powder is uniformly dissolved, and storing in a refrigerator at 4 ℃ for later use. Weighing 1.1g of chitosan, dissolving in 100mL of dimethyl sulfoxide (chemical purity), magnetically stirring at normal temperature for 1h until the chitosan is uniformly dissolved, and storing in a refrigerator at 4 ℃ for later use.
(2) Weighing 2.2g of p-aldehyde benzoic acid, dissolving in 20mL of dimethyl sulfoxide (chemical purity), magnetically stirring at normal temperature for 0.5h until the p-aldehyde benzoic acid is uniformly dissolved, and storing in a refrigerator at 4 ℃ for later use. 0.66g of 4-Dimethylaminopyridine (DMAP) is weighed and dissolved in 100mL of dimethyl sulfoxide (chemical purity), magnetic stirring is carried out at normal temperature for 0.5h until the solution is uniform, and the solution is stored in a refrigerator at the temperature of 4 ℃ for standby. Weighing 1.1g Dicyclohexylcarbodiimide (DCC) and dissolving in 10mL dimethyl sulfoxide (chemical purity), magnetically stirring at normal temperature for 0.5h until the solution is uniform, and storing in a refrigerator at 4 ℃ for later use.
(3) And (3) weighing 50mL of the chitosan solution obtained in the step (1) into a round-bottom flask, respectively weighing 20mL of p-aldehyde benzoic acid solution, 10mL of DMAP solution and 10mL of DCC solution prepared in the step (2) under magnetic stirring, sequentially adding the solutions into the chitosan solution, and stirring the two solutions for 5min after adding the two solutions. After all the addition was completed, the mixture was stirred at room temperature for 1 day. And after the reaction is finished, adding 30mL of deionized water for settling for 12h, alternately washing for 5 times by using anhydrous ethanol and the deionized water, and performing suction filtration at normal temperature and normal pressure to obtain light yellow OCS powder.
(4) 5mL of HAuCl with a concentration of 1mmol/L was measured4Adding the solution into a round-bottom flask, magnetically stirring at 25 deg.C for 5s, adding 25mL of 0.05mol/L surfactant CTAB aqueous solution, stirring for 5s, adding 1mL of 5mmol/L NaBH4Stirring the aqueous solution for 60s to obtain the gold seed solution.
(5) 10mL of HAuCl at a concentration of 1mmol/L was measured4Adding the solution into a round-bottom flask, magnetically stirring at 25 deg.C for 5s, adding 25mL of surfactant CTAB aqueous solution with concentration of 0.05mol/L, stirring for 5s, and sequentially adding 0.6mL of AgNO with concentration of 7mmol/L3Adding the solution and 1mL of Vc aqueous solution with the concentration of 80mmol/L, and stirring for 5s respectively to obtain the nano Au growth solution.
(6) Measuring 2mL of the seed solution obtained in the step (4), adding 2mL of the growth solution obtained in the step (5), magnetically stirring at 25 ℃ for 5s, standing at normal temperature for 18h, and centrifuging the mixed solution at the speed of 5000r/min for 10min after the gold rod grows stably. And after the centrifugation is finished, alternately washing the Au rod by using absolute ethyl alcohol and deionized water for 5 times, and performing suction filtration at normal temperature and normal pressure to obtain the Au rod powder.
(7) And (3) weighing 0.02g of OCS powder obtained in the step (3), dissolving in 1mL of deionized water, carrying out ultrasonic oscillation for 5min until the OCS powder is uniformly dispersed, then adding 0.01g of nano Au bar powder obtained in the step (6), and carrying out magnetic stirring for 1h to prepare a nano Au bar mixed solution.
(8) 0.04g of MnCl is weighed2·4H2Dissolving O in 4mL of deionized water, magnetically stirring at normal temperature for 0.5h until the O is uniformly dissolved, and standing at normal temperature for later use.
(9) Measuring 10mL of the carboxymethyl chitosan solution obtained in the step (1) into a beaker, adding 1mL of the nano Au bar mixed solution obtained in the step (7) under magnetic stirring, and fillingStirring for 2 hours; then, 2mL of Mn obtained in step (8) was slowly added2+Stirring the solution at normal temperature for 20h to obtain the composite hydrogel.
The SEM image of the composite hydrogel obtained in this example is shown in FIG. 1, and the analysis of the SEM image shows that the composite hydrogel has a porous three-dimensional network structure, and Mn is chelated by carboxymethyl chitosan (CMC) in the whole crosslinking system2+As a structural support. Wherein the cross-linking point with rod-shaped protrusion is a nano gold rod coated by the surface of aldehyde chitosan (OCS), and the OCS and CMC have the functions of polymer combination and winding and are inserted into CMC to chelate Mn2+In the overall structure of (a). And the tiny particles adsorbed on the surface of the polymer may be uncached Mn ions or nano-gold particles (because the method for preparing the nano-gold rod according to the invention may cause the gold rod to contain nano-gold particle impurities).
Example 2
(1) Weighing 8g of carboxymethyl chitosan powder, dissolving in 100mL of deionized water, magnetically stirring at normal temperature for 5h until the carboxymethyl chitosan powder is uniformly dissolved, and storing in a refrigerator at 4 ℃ for later use. 5.5g of chitosan is weighed and dissolved in 100mL of dimethyl sulfoxide (chemical purity), magnetic stirring is carried out for 6h at normal temperature until the chitosan is dissolved uniformly, and the mixture is placed in a refrigerator at 4 ℃ for storage for later use.
(2) Weighing 6.6g of p-aldehyde benzoic acid, dissolving in 20mL of dimethyl sulfoxide (chemical purity), magnetically stirring at normal temperature for 2h until the p-aldehyde benzoic acid is uniformly dissolved, and storing in a refrigerator at 4 ℃ for later use. Weighing 1.32g of 4-Dimethylaminopyridine (DMAP) and dissolving in 100mL of dimethyl sulfoxide (chemical purity), magnetically stirring for 2h at normal temperature until the solution is uniformly dissolved, and storing in a refrigerator at 4 ℃ for later use. 3.85g Dicyclohexylcarbodiimide (DCC) is weighed and dissolved in 10mL dimethyl sulfoxide (chemical purity), stirred by magnetic force for 2h at normal temperature until the solution is uniform, and then placed in a refrigerator at 4 ℃ for storage for later use.
(3) And (3) weighing 50mL of the chitosan solution obtained in the step (1) into a round-bottom flask, respectively weighing 20mL of p-aldehyde benzoic acid solution, 10mL of DMAP solution and 10mL of DCC solution prepared in the step (2) under magnetic stirring, sequentially adding the solutions into the chitosan solution, and stirring the two solutions for 30min after adding the two solutions. After all the addition was completed, the mixture was stirred at room temperature for 4 days. And after the reaction is finished, adding 70mL of deionized water for settling for 48h, alternately washing for 10 times by using anhydrous ethanol and the deionized water, and performing suction filtration at normal temperature and normal pressure to obtain light yellow OCS powder.
(4) 9mL of HAuCl at a concentration of 1mmol/L was measured4Adding the solution into a round-bottom flask, magnetically stirring at 40 deg.C for 60s, adding 25mL of 2mol/L surfactant CTAB aqueous solution, stirring for 60s, adding 1mL of 12mmol/L NaBH4Stirring the aqueous solution for 5s to obtain the gold seed solution.
(5) 15mL of HAuCl with a concentration of 1mmol/L was measured4Adding the solution into a round-bottom flask, magnetically stirring at 40 deg.C for 60s, adding 25mL of 2mol/L surfactant CTAB aqueous solution, stirring for 60s, and sequentially adding 0.6mL of 18mmol/L AgNO3Adding the solution and 1mL of Vc aqueous solution with the concentration of 150mmol/L, and stirring for 60s respectively to obtain the nano Au growth solution.
(6) Measuring 2mL of the seed solution obtained in the step (4), adding 10mL of the growth solution obtained in the step (5), magnetically stirring at 40 ℃ for 60s, standing at normal temperature for 6h, and centrifuging the mixed solution at 8000r/min for 20min after the gold rod grows stably. And after the centrifugation is finished, alternately washing the Au rod by using absolute ethyl alcohol and deionized water for 10 times, and performing suction filtration at normal temperature and normal pressure to obtain the Au rod powder.
(7) And (3) weighing 0.07g of OCS powder obtained in the step (3), dissolving in 1mL of deionized water, carrying out ultrasonic oscillation for 10min until the OCS powder is uniformly dispersed, then adding 0.1g of nano Au bar powder obtained in the step (6), and carrying out magnetic stirring for 3h to prepare a nano Au bar mixed solution.
(8) 0.32g of MnCl is weighed2·4H2Dissolving O in 4mL of deionized water, magnetically stirring for 2h at normal temperature until the O is uniformly dissolved, and standing at normal temperature for later use.
(9) Weighing 10mL of the carboxymethyl chitosan solution obtained in the step (1) into a beaker, adding 1mL of the nano Au bar mixed solution obtained in the step (7) under magnetic stirring, and fully stirring for 5 hours; then, 2mL of Mn obtained in step (8) was slowly added2+Stirring the solution for 4 hours at normal temperature to obtain the composite hydrogel.
FIG. 2 shows the swelling properties of the composite hydrogel prepared in this example. From the swelling curve, the composite gel has good swelling performance, and the swelling equilibrium rate can reach 830%. Due to the porous network structure and the addition of the rigid nano filler, the gel has better moisture absorption capacity after freeze-drying, increases the stress resistance and can keep the swelling balance within a certain time.
FIG. 3 shows the dissolution behavior of the composite hydrogel prepared in this example. From the degradation curve, the composite gel has degradability, can keep 52.56% of the original gel mass after 7 days of degradation, but reduces the gel mass to below 10% after 14 days, which indicates that the gel is expected to be used as a drug-loaded material in organisms, and can reach the degradation requirement within a certain time after slowly releasing drugs, thereby avoiding long-term residue in the organisms.
Example 3
(1) Weighing 6g of carboxymethyl chitosan powder, dissolving in 100mL of deionized water, magnetically stirring at normal temperature for 4h until the carboxymethyl chitosan powder is uniformly dissolved, and storing in a refrigerator at 4 ℃ for later use. Weighing 2.5g of chitosan, dissolving in 100mL of dimethyl sulfoxide (chemical purity), magnetically stirring at normal temperature for 2h until the chitosan is uniformly dissolved, and storing in a refrigerator at 4 ℃ for later use.
(2) Weighing 2.5g of p-aldehyde benzoic acid, dissolving in 20mL of dimethyl sulfoxide (chemical purity), magnetically stirring at normal temperature for 1h until the p-aldehyde benzoic acid is uniformly dissolved, and storing in a refrigerator at 4 ℃ for later use. 0.8g of 4-Dimethylaminopyridine (DMAP) is weighed and dissolved in 100mL of dimethyl sulfoxide (chemical purity), magnetic stirring is carried out at normal temperature for 0.5h until the solution is uniform, and the solution is placed in a refrigerator at the temperature of 4 ℃ for storage for later use. Weighing 1.68g Dicyclohexylcarbodiimide (DCC) and dissolving in 10mL dimethyl sulfoxide (chemical purity), magnetically stirring at normal temperature for 1h until the solution is uniform, and storing in a refrigerator at 4 ℃ for later use.
(3) And (3) weighing 50mL of the chitosan solution obtained in the step (1) into a round-bottom flask, respectively weighing 20mL of p-aldehyde benzoic acid solution, 10mL of DMAP solution and 10mL of DCC solution prepared in the step (2) under magnetic stirring, sequentially adding the solutions into the chitosan solution, and stirring for 10min after the first two solutions are added. After all the addition was completed, the mixture was stirred at room temperature for 1 day. And after the reaction is finished, adding 40mL of deionized water for settling for 18h, alternately washing with absolute ethyl alcohol and deionized water, and performing suction filtration at normal temperature and normal pressure to obtain light yellow OCS powder.
(4) 8mL of the solution having a concentration of 1mmol/L was measuredHAuCl4Adding the solution into a round-bottom flask, magnetically stirring at 35 deg.C for 10s, adding 25mL of 1mol/L surfactant CTAB aqueous solution, stirring for 10s, adding 1mL of 10mmol/L NaBH4Stirring the aqueous solution for 20s to obtain the gold seed solution.
(5) 12mL of HAuCl at a concentration of 1mmol/L was measured4Adding the solution into a round-bottom flask, magnetically stirring at 35 deg.C for 10s, adding 25mL of surfactant CTAB aqueous solution with concentration of 1mol/L, stirring for 10s, and sequentially adding 0.6mL of AgNO with concentration of 10mmol/L3Adding the solution and 1mL of Vc aqueous solution with the concentration of 90mmol/L, and stirring for 20s respectively to obtain the nano Au growth solution.
(6) Measuring 2mL of the seed solution obtained in the step (4), adding 5mL of the growth solution obtained in the step (5), magnetically stirring at 35 ℃ for 15s, standing at normal temperature for 8h, and centrifuging the mixed solution at the speed of 6000r/min for 10min after the gold rod grows stably. And after the centrifugation is finished, alternately washing the Au rod by using absolute ethyl alcohol and deionized water for 7 times, and performing suction filtration at normal temperature and normal pressure to obtain the Au rod powder.
(7) And (3) weighing 0.03g of OCS powder obtained in the step (3), dissolving in 1mL of deionized water, carrying out ultrasonic oscillation for 10min until the OCS powder is uniformly dispersed, then adding 0.06g of nano Au bar powder obtained in the step (6), and carrying out magnetic stirring for 1.5h to prepare a nano Au bar mixed solution.
(8) 0.12g of MnCl is weighed2·4H2Dissolving O in 4mL of deionized water, magnetically stirring at normal temperature for 0.5h until the O is uniformly dissolved, and standing at normal temperature for later use.
(9) Weighing 10mL of the carboxymethyl chitosan solution obtained in the step (1) into a beaker, adding 1mL of the nano Au bar mixed solution obtained in the step (7) under magnetic stirring, and fully stirring for 2 hours; then, 2mL of Mn obtained in step (5) was slowly added2+Stirring the solution at normal temperature for 16h to obtain the composite hydrogel.
Example 4
(1) Weighing 4g of carboxymethyl chitosan powder, dissolving in 100mL of deionized water, magnetically stirring at normal temperature for 1h until the carboxymethyl chitosan powder is uniformly dissolved, and storing in a refrigerator at 4 ℃ for later use. Weighing 4.5g of chitosan, dissolving in 100mL of dimethyl sulfoxide (chemical purity), magnetically stirring at normal temperature for 3h until the chitosan is uniformly dissolved, and storing in a refrigerator at 4 ℃ for later use.
(2) Weighing 6g of p-aldehyde benzoic acid, dissolving the p-aldehyde benzoic acid in 20mL of dimethyl sulfoxide (chemical purity), magnetically stirring the p-aldehyde benzoic acid for 2 hours at normal temperature until the p-aldehyde benzoic acid is uniformly dissolved, and storing the p-aldehyde benzoic acid in a refrigerator at 4 ℃ for later use. 0.9g of 4-Dimethylaminopyridine (DMAP) is weighed and dissolved in 100mL of dimethyl sulfoxide (chemical purity), the mixture is magnetically stirred for 1h at normal temperature until the mixture is uniformly dissolved, and the mixture is placed in a refrigerator at the temperature of 4 ℃ for storage for later use. Weighing 1.5g Dicyclohexylcarbodiimide (DCC) and dissolving in 10mL dimethyl sulfoxide (chemical purity), magnetically stirring at normal temperature for 2h until the solution is uniform, and storing in a refrigerator at 4 ℃ for later use.
(3) And (3) weighing 50mL of the chitosan solution obtained in the step (1) into a round-bottom flask, respectively weighing 20mL of p-aldehyde benzoic acid solution, 10mL of DMAP solution and 10mL of DCC solution prepared in the step (2) under magnetic stirring, sequentially adding the solutions into the chitosan solution, and stirring the two solutions for 25min after adding the two solutions. After all the addition was completed, the mixture was stirred at room temperature for 2 days. And after the reaction is finished, adding 70mL of deionized water for settling for 35h, alternately washing with anhydrous ethanol and deionized water, and performing suction filtration at normal temperature and normal pressure to obtain light yellow OCS powder.
(4) 6mL of HAuCl at a concentration of 1mmol/L was measured4Adding the solution into a round-bottom flask, magnetically stirring at 30 ℃ for 15s, adding 25mL of a 0.8mol/L surfactant CTAB aqueous solution, stirring for 15s, adding 1mL of 7mmol/L NaBH4Stirring the aqueous solution for 45s to obtain the gold seed solution.
(5) 13mL of HAuCl at a concentration of 1mmol/L was measured4Adding the solution into a round-bottom flask, magnetically stirring at 30 deg.C for 15s, adding 25mL of surfactant CTAB aqueous solution with concentration of 0.8mol/L, stirring for 15s, and sequentially adding 0.6mL of AgNO with concentration of 8mmol/L3Adding the solution and 1mL of Vc aqueous solution with the concentration of 85mmol/L, and stirring for 20s respectively to obtain the nano Au growth solution.
(6) Measuring 2mL of the seed solution obtained in the step (4), adding 3mL of the growth solution obtained in the step (5), magnetically stirring at 30 ℃ for 45s, standing at normal temperature for 9h, and centrifuging the mixed solution at 7000r/min for 20min after the gold rod grows stably. And after the centrifugation is finished, alternately washing the Au rod by using absolute ethyl alcohol and deionized water for 9 times, and performing suction filtration at normal temperature and normal pressure to obtain the Au rod powder.
(7) And (3) weighing 0.04g of OCS powder obtained in the step (3), dissolving in 1mL of deionized water, carrying out ultrasonic oscillation for 10min until the OCS powder is uniformly dispersed, then adding 0.05g of nano Au bar powder obtained in the step (6), and carrying out magnetic stirring for 3h to prepare a nano Au bar mixed solution.
(8) 0.16g of MnCl is weighed2·4H2Dissolving O in 4mL of deionized water, magnetically stirring for 1h at normal temperature until the O is uniformly dissolved, and standing at normal temperature for later use.
(9) Weighing 10mL of the carboxymethyl chitosan solution obtained in the step (1) into a beaker, adding 1mL of the nano Au bar mixed solution obtained in the step (7) under magnetic stirring, and fully stirring for 2 hours; then, 2mL of Mn obtained in step (8) was slowly added2+Stirring the solution at normal temperature for 6h to obtain the composite hydrogel.
Example 5
(1) Weighing 3g of carboxymethyl chitosan powder, dissolving in 100mL of deionized water, magnetically stirring at normal temperature for 1h until the carboxymethyl chitosan powder is uniformly dissolved, and storing in a refrigerator at 4 ℃ for later use. 3.2g of chitosan is weighed and dissolved in 100mL of dimethyl sulfoxide (chemical purity), the mixture is magnetically stirred for 2 hours at normal temperature until the mixture is uniformly dissolved, and the mixture is placed in a refrigerator at 4 ℃ for storage for later use.
(2) Weighing 3g of p-aldehyde benzoic acid, dissolving in 20mL of dimethyl sulfoxide (chemical purity), magnetically stirring at normal temperature for 1h until the p-aldehyde benzoic acid is uniformly dissolved, and storing in a refrigerator at 4 ℃ for later use. 0.7g of 4-Dimethylaminopyridine (DMAP) is weighed and dissolved in 100mL of dimethyl sulfoxide (chemical purity), the mixture is magnetically stirred for 1h at normal temperature until the mixture is uniformly dissolved, and the mixture is placed in a refrigerator at the temperature of 4 ℃ for storage for later use. Weighing 1.35g of Dicyclohexylcarbodiimide (DCC), dissolving in 10mL of dimethyl sulfoxide (chemical purity), magnetically stirring at normal temperature for 2h until the solution is uniformly dissolved, and storing in a refrigerator at 4 ℃ for later use.
(3) And (3) weighing 50mL of the chitosan solution obtained in the step (1) into a round-bottom flask, respectively weighing 20mL of p-aldehyde benzoic acid solution, 10mL of DMAP solution and 10mL of DCC solution prepared in the step (2) under magnetic stirring, sequentially adding the solutions into the chitosan solution, and stirring for 10min after the first two solutions are added. After all the addition was completed, the mixture was stirred at room temperature for 3 days. And after the reaction is finished, adding 50mL of deionized water for settling for 40h, alternately washing with absolute ethyl alcohol and deionized water, and performing suction filtration at normal temperature and normal pressure to obtain light yellow OCS powder.
(4) 6mL of HAuCl at a concentration of 1mmol/L was measured4Adding the solution into a round-bottom flask, magnetically stirring at 32 deg.C for 25s, adding 25mL of 0.1mol/L surfactant CTAB aqueous solution, stirring for 25s, adding 1mL of 6mmol/L NaBH4Stirring the aqueous solution for 30s to obtain the gold seed solution.
(5) 14mL of HAuCl at a concentration of 1mmol/L was measured4Adding the solution into a round-bottom flask, magnetically stirring at 32 deg.C for 25s, adding 25mL of surfactant CTAB aqueous solution with concentration of 0.1mol/L, stirring for 25s, and sequentially adding 0.6mL of AgNO with concentration of 9mmol/L3Adding the solution and 1mL of Vc aqueous solution with the concentration of 95mmol/L, and stirring for 15s respectively to obtain the nano Au growth solution.
(6) Measuring 2mL of the seed solution obtained in the step (4), adding 4mL of the growth solution obtained in the step (5), magnetically stirring at 32 ℃ for 45s, standing at normal temperature for 15h, and centrifuging the mixed solution at 8000r/min for 20min after the gold rod grows stably. And after the centrifugation is finished, alternately washing the Au rod by using absolute ethyl alcohol and deionized water for 10 times, and performing suction filtration at normal temperature and normal pressure to obtain the Au rod powder.
(7) And (3) weighing 0.05g of OCS powder obtained in the step (3), dissolving in 1mL of deionized water, carrying out ultrasonic oscillation for 10min until the OCS powder is uniformly dispersed, then adding 0.04g of nano Au bar powder obtained in the step (6), and carrying out magnetic stirring for 2h to prepare a nano Au bar mixed solution.
(8) 0.08g of MnCl is weighed2·4H2Dissolving O in 4mL of deionized water, magnetically stirring at normal temperature for 0.5h until the O is uniformly dissolved, and standing at normal temperature for later use.
(9) Weighing 10mL of the carboxymethyl chitosan solution obtained in the step (1) into a beaker, adding 1mL of the nano Au bar mixed solution obtained in the step (7) under magnetic stirring, and fully stirring for 2 hours; then, 2mL of Mn obtained in step (8) was slowly added2+Stirring the solution at normal temperature for 20h to obtain the composite hydrogel.
FIG. 4 shows the in vitro cytotoxic effect of the composite hydrogel prepared in this example. Tumor cells (293 cells) were cultured on the surface of the complex gel (culture conditions: high-glucose DMEM + 10% FBS calf serum, 37 ℃) for 1 day and 4 days, and the effect of fluorescent staining (AO/PI staining) was observed. In the figure, the green part is shown as live cells and the red part is shown as dead cells. From the staining results, the amount of dead cells was less, indicating that the material was less bio-toxic. With the increase of time, the amount of the cells inoculated on the surface of the material is gradually increased, which indicates that the cells have better proliferation capacity on the surface of the material.
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (9)
1. A preparation method of a high-molecular self-healing gel integrating magnetic resonance imaging and photothermal therapy is characterized by comprising the following steps:
(1) adding p-aldehyde benzoic acid, 4-dimethylaminopyridine and dicyclohexylcarbodiimide into the chitosan solution, stirring for 5-30 min, then reacting for 1-4 days, precipitating, washing, and performing suction filtration to obtain aldehyde chitosan;
(2) at 25-40 ℃ to HAuCl4Adding a surfactant into the solution, stirring for 5-60 s, and adding NaBH4Stirring the solution for 5-60 s to obtain Au seed solution;
(3) at 25-40 ℃ to HAuCl4Adding a surfactant into the solution, stirring for 5-60 s, and adding AgNO3Stirring the solution for 5-60 s, adding a reducing agent solution, and stirring for 5-60 s to obtain a nano Au growth solution;
(4) adding the nano Au growth solution into the Au seed solution, stirring for 5-60 s at 25-40 ℃, standing for 6-18 h at normal temperature, centrifuging after the gold rod grows stably, washing, and performing suction filtration to obtain nano Au rod powder;
(5) dissolving the aldehyde chitosan in water, uniformly dispersing, adding the nano Au bar powder, and stirring for 1-3 h to obtain a nano Au bar mixed solution;
(6) to the direction ofAdding a nano Au bar mixed solution into the carboxymethyl chitosan solution, stirring for 2-5 h, and adding MnCl2·4H2And stirring the O aqueous solution for 4-20 hours to obtain the high-molecular self-healing composite hydrogel.
2. The method for preparing the self-healing polymer gel integrating magnetic resonance imaging and photothermal therapy according to claim 1, wherein the chitosan solution in the step (1) comprises chitosan, p-aldehyde benzoic acid, 4-dimethylaminopyridine and dicyclohexylcarbodiimide in a mass ratio of (5-25): (20-60): (0.6-1.2): (10-35);
HAuCl in the step (2)4HAuCl in solution4Surfactants and NaBH4NaBH in solution4The molar ratio of (5-9) mmol: (1.25-50) mol: (5-12) mmol.
3. The method for preparing self-healing polymer gel integrating magnetic resonance imaging and photothermal therapy according to claim 1, wherein the HAuCl in step (3) is added4HAuCl in solution4Surfactant, AgNO3AgNO in solution3And the molar ratio of the reducing agent in the reducing agent solution is (10-15) mmol: (1.25-50) mol: (4.2-10.8) mmol: (80-150) mmol;
and (4) the volume ratio of the nano Au growth solution to the Au seed solution is (1-5): 1.
4. the method for preparing the self-healing polymer gel integrating magnetic resonance imaging and photothermal therapy according to claim 1, wherein the mass ratio of the aldehyde chitosan to the nano Au rod powder in the step (5) is (2-7): (1-10);
carboxymethyl chitosan in the carboxymethyl chitosan solution, and nano Au bars and MnCl in the nano Au bar mixed solution in the step (6)2·4H2MnCl in aqueous O solution2·4H2The mass ratio of O is (20-80): (1-10): (2-16).
5. The method for preparing the self-healing polymer gel integrating magnetic resonance imaging and photothermal therapy according to claim 1, wherein the concentration of the chitosan solution in the step (1) is 1-5 wt%, the molecular weight of chitosan in the chitosan solution is 800-1000, and the degree of deacetylation is 75-85%;
adding p-aldehyde benzoic acid in the step (1) in the form of a p-aldehyde benzoic acid solution, wherein the concentration of the p-aldehyde benzoic acid solution is 10-30 wt%; the 4-dimethylaminopyridine is added in the form of a 4-dimethylaminopyridine solution, and the concentration of the 4-dimethylaminopyridine solution is 0.6-1.2 wt%; the dicyclohexylcarbodiimide is added in the form of a dicyclohexylcarbodiimide solution, and the concentration of the dicyclohexylcarbodiimide solution is 10-35 wt%.
6. The method for preparing self-healing polymer gel integrating magnetic resonance imaging and photothermal therapy according to claim 1, wherein the HAuCl is obtained in the steps (2) and (3)4The concentration of the solution is 0.5-5 mmol/L; NaBH in step (2)4The concentration of the solution is 5-12 mmol/L; the surfactant in the steps (2) and (3) is cetyl trimethyl ammonium bromide, and is added in the form of surfactant solution, and the concentration of the surfactant solution is 0.05-2 mol/L;
the reducing agent in the reducing agent solution in the step (3) is vitamin C and NaBH4At least one of; the concentration is 80-150 mmol/L; AgNO described in step (3)3The concentration of the solution is 7-18 mmol/L.
7. The method for preparing a self-healing polymer gel integrating magnetic resonance imaging and photothermal therapy according to claim 1, wherein the concentration of the solution formed by dissolving the aldehyde chitosan in water in step (5) is 2-7 wt%; the concentration of the nano Au bar powder in the system in the step (5) is 1-10 wt%;
the concentration of the carboxymethyl chitosan solution in the step (6) is 2-8 wt%, wherein the molecular weight of the carboxymethyl chitosan is 2000, and the substitution degree is 80-85%; MnCl in the step (6)2·4H2The concentration of the O aqueous solution is 1~8 wt%。
8. The method for preparing a self-healing polymer gel integrating magnetic resonance imaging and photothermal therapy according to claim 1, wherein the stirring and the reaction in step (1) are both performed at room temperature; the solvent used in the reaction is dimethyl sulfoxide; the precipitation time is 12-48 h, the precipitating agent is deionized water, and the volume ratio of the reaction product mixed solution to the added precipitating agent is 9: (3-7);
the solvents of the solutions involved in the steps (2) and (3) are all water; the rotating speed of the centrifugation in the step (4) is 5000-8000 r/min, and the time is 10-20 min;
washing in the steps (1) and (4) refers to repeatedly washing with absolute ethyl alcohol and deionized water for 5-10 times until the solution is colorless; the suction filtration is performed at normal temperature and normal pressure;
and (5) performing ultrasonic oscillation in the uniform dispersion mode, wherein the ultrasonic time is 5-10 min.
9. The self-healing polymer gel integrating magnetic resonance imaging and photothermal therapy, prepared by the method of any one of claims 1 to 8.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2740491A1 (en) * | 2012-12-05 | 2014-06-11 | Institut Curie | Conjugates of the B-subunit of shiga toxin for use as contrasting agents for imaging and therapy |
| CN104258426A (en) * | 2014-09-17 | 2015-01-07 | 武汉大学 | Nuclear magnetic resonance visual injectable pH sensitive self-repairing water gel as well as preparation method and application thereof |
| CN104910396A (en) * | 2015-06-03 | 2015-09-16 | 西安交通大学 | Injectable double-crosslinked hyaluronic acid aquagel and preparation method thereof |
| CN110522718A (en) * | 2019-09-11 | 2019-12-03 | 大连医科大学 | A kind of injectable thermosensitive hydrogel and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102743768B (en) * | 2012-07-03 | 2014-07-09 | 中国科学院宁波材料技术与工程研究所 | Stealth contrast-enhancing material for early diagnosis of tumors and preparation method thereof |
| US20160367705A1 (en) * | 2015-06-16 | 2016-12-22 | New York University | Nanoparticles comprised of shells associated with charged entities and formed from monomers and methods of making and using nanoparticles |
-
2020
- 2020-04-17 CN CN202010306750.7A patent/CN111558040B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2740491A1 (en) * | 2012-12-05 | 2014-06-11 | Institut Curie | Conjugates of the B-subunit of shiga toxin for use as contrasting agents for imaging and therapy |
| CN104258426A (en) * | 2014-09-17 | 2015-01-07 | 武汉大学 | Nuclear magnetic resonance visual injectable pH sensitive self-repairing water gel as well as preparation method and application thereof |
| CN104910396A (en) * | 2015-06-03 | 2015-09-16 | 西安交通大学 | Injectable double-crosslinked hyaluronic acid aquagel and preparation method thereof |
| CN110522718A (en) * | 2019-09-11 | 2019-12-03 | 大连医科大学 | A kind of injectable thermosensitive hydrogel and preparation method thereof |
Non-Patent Citations (3)
| Title |
|---|
| Tumor-targeting nanogel that can function independently for both photodynamic and photothermal therapy and its synergy from the procedure of PDT followed by PTT;Ja-Young Kim,et al.;《Journal of Controlled Release》;20130713;第171卷;第113-121页 * |
| Visualization of in situ hydrogels by MRI in vivo;Jia Liu,et al.;《J. Mater. Chem. B》;20160113;第4卷;第1343-1353页 * |
| 磁性水凝胶作为药物载体的应用研究进展;韩晓东等;《材料导报Ａ：综述篇》;20170831;第31卷(第8期);第30-35页 * |
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