CN108096214B - Magnetotactic bacteria quantum dot microcapsule and preparation method thereof - Google Patents
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Abstract
The invention provides a magnetotactic bacteria quantum dot microcapsule, wherein the inner core of the microcapsule is magnetosome, and the surface of the magnetosome is coated with a uniform and compact mixture of chitosan oligosaccharide/gamma-polyglutamic acid/carbon quantum dots; the mass ratio of the magnetosome to the chitosan, the gamma-polyglutamic acid and the carbon quantum dots is (1: 1) - (3: 10) - (20): 1. the preparation method of the magnetotactic bacteria quantum dot microcapsule is simple to operate, the obtained magnetosome and the carbon quantum dot intelligent microcapsule have typical core-shell structures, and the quantum dot microcapsule has targeting and slow-release capabilities and has great clinical application prospects.
Description
Technical Field
The invention relates to the field of biomedicine, in particular to a magnetotactic bacteria quantum dot microcapsule and a preparation method of the magnetotactic bacteria quantum dot microcapsule.
Background
The mode of drug delivery has a crucial impact on the therapeutic efficacy of cancer, with tumor-targeted drug delivery being a major challenge. As the research of nanotechnology in the biomedical field is deepened, magnetic nanomaterials are receiving much attention. Magnetotactic bacteria (Magnetosome) are bacteria that can make directional motion under the action of external magnetic field and form nano magnetic particles in vivo, and in recent years, Magnetosome and Magnetosome have become new biological resources, and have been widely studied in many disciplines such as materials science, medicine, biology, physics, geology, etc., and in bionicsAnd applied to a plurality of fields such as ecology, medicine, geology, industrial treatment, sanitary inspection and the like. Magnetic bacteria in vivo synthesis of chain-shaped arranged Fe with outer membrane coating3O4Or Fe3S4Magnetic particle-magnetosome. The magnetosome particles are single-magnetic-domain crystals, are uniform in size, nanoscale (20-120 nm), have large specific surface values, are coated with a biological membrane outside the particles, do not produce cytotoxicity, and have excellent biocompatibility, but the naked magnetosome is easy to induce aggregation among the particles due to the fact that the magnetosome has high specific surface area, so that the particle size is increased, the stability is poor, and the requirements of biomedical application cannot be met. Therefore, the surface modification of the magnetic nanostructure is necessary to reduce the interparticle interaction and improve the water solubility, stability and surface functionality.
Carbon is one of the most abundant elements in nature and also the most basic element constituting a living body. The carbon quantum dots are novel nano carbon materials which are composed of dispersed spheroidal particles, have the size of less than 10nm and have fluorescence properties. Compared with the traditional semiconductor quantum dot, the carbon quantum dot not only has the luminescent performance and the nanometer size characteristic similar to the traditional quantum dot, but also has the characteristics of good water solubility, chemical inertness, easy functionalization, high photobleaching resistance, low toxicity, good biocompatibility and the like, so that the carbon quantum dot has attracted extensive attention in different research fields.
Chitosan oligosaccharide is the second most renewable natural high molecular compound next to cellulose in the world, and has the advantages of biodegradability, nontoxicity, bioactivity, biocompatibility, antibacterial property and the like. The molecule contains hydroxyl and amino simultaneously, has more active property, and can carry out coupling, activation and modification on the molecule. The gamma-polyglutamic acid is a water-soluble biodegradable high molecular substance, has the characteristics of edibility, no toxicity, cohesiveness, moisture retention and the like, and the application field of the gamma-polyglutamic acid covers a plurality of aspects of medicines, chemical engineering, foods, cosmetics, daily chemical products and the like. Particularly in the field of medicine, as a medicine targeting carrier, the gamma-polyglutamic acid can be degraded into endogenous amino acid in a human body, and has no toxic or side effect on the human body. Meanwhile, as more side chain carboxyl exists, the modified compound can be used as a drug carrier.
How to provide a drug delivery mode for tumor-targeted drug delivery is a problem to be solved urgently at present.
Disclosure of Invention
The invention provides a magnetotactic bacteria quantum dot microcapsule and a preparation method thereof, wherein magnetosomes, carbon quantum dots and biological materials are mixed to prepare a sustained-release microcapsule, and the microcapsule is used as an oral sustained-release preparation according to different treatment purposes, can also be used for preparing a sustained-release preparation of targeted drug loading, can be applied to the field of biological medicine, and realizes magnetic fixation targeted sustained-release drug delivery.
The technical scheme of the invention is realized as follows:
a magnetotactic bacteria quantum dot microcapsule, the inner core of the microcapsule is a single magnetic domain structure of magnetosome, the surface of the magnetosome is coated with a mixture of chitosan oligosaccharide, gamma-polyglutamic acid and carbon quantum dots; the mass ratio of the magnetosome to the chitosan, the gamma-polyglutamic acid and the carbon quantum dots is as follows:
magnetosome 1 weight part
1-3 parts of chitosan
10-20 parts of gamma-polyglutamic acid
And 1 part by weight of carbon quantum dots.
Optionally, the microcapsules have a particle size of less than 100 nm.
Optionally, the microcapsules have a particle size of 50 to 80nm and a polydispersity of 0.2 or less.
Optionally, the molecular weight of the chitosan oligosaccharide is 1KD, the molecular weight of the gamma-polyglutamic acid is 40KD, and the carbon quantum dots are prepared by taking natural graphene as a raw material.
Optionally, the microcapsules have a particle size of 50 to 80nm and a polydispersity of 0.2 or less.
Optionally, the particle size of the magnetosome is 20-50 nm.
Optionally, the loading drug is doxorubicin.
The invention also provides a preparation method of the magnetotactic bacteria quantum dot microcapsule, which comprises the following steps:
adding natural graphene into a mixed solution of concentrated sulfuric acid and concentrated nitric acid, ultrasonically dispersing the mixture uniformly, and stirring and refluxing at 100 ℃; cooling the obtained brownish black solution to room temperature, and then adding deionized water for dilution; then adding sodium carbonate to neutralize the residual acid until the pH of the solution is 8; concentrating the obtained solution by rotary evaporation, filtering and removing precipitated inorganic salt, and dialyzing the collected filtrate by using a dialysis bag with the cut-off molecular weight of 8000-14000 to obtain an aqueous solution of pure carbon quantum dots; freezing and drying the aqueous solution of the carbon quantum dots to obtain carbon quantum dot solids, and dispersing the carbon quantum dot solids in the aqueous solution again;
adding 1/3-2/3 amount of chitosan oligosaccharide into the dispersion, mixing, reacting for 1h at 95 ℃, performing ultrasonic treatment and centrifugation, performing ball milling treatment on large particles of chitosan oligosaccharide in liquid nitrogen, adding the rest of chitosan oligosaccharide, reacting for 1h at 60 ℃, performing freeze drying, dissolving in water again, adding magnetosomes, stirring uniformly, adding gamma-polyglutamic acid, and performing magnetic stirring to obtain composite microcapsules;
and (3) washing the composite microcapsule with absolute ethyl alcohol, carrying out magnet separation, and finally drying in vacuum at 60 ℃ to obtain the magnetotactic bacteria quantum dot microcapsule.
Optionally, the concentration of carbon quantum dots in the aqueous solution is 0.2 mg/mL.
Optionally, in the step (2), the large-particle liquid is ball-milled for 120-150 min to a particle size of 50-100 nm by using liquid nitrogen.
The invention has the beneficial effects that:
(1) the utilized chitosan oligosaccharide has the characteristics of bacteriostasis, no toxicity, good biocompatibility and the like; the gamma-polyglutamic acid has the characteristics of moisture retention, no toxicity, good biocompatibility and the like; the carbon quantum dots not only have the luminescent performance and the nano-size characteristic similar to those of the traditional quantum dots, but also have the characteristics of good water solubility, chemical inertness, easy functionalization, high photobleaching resistance, low toxicity, good biocompatibility and the like; the magnetosome particles are single magnetic domain crystals, have larger specific surface value, are coated with biological films outside the particles, do not produce cytotoxicity, have excellent biocompatibility, generate particles below 100nm after cross-linking reaction of four substances, and the method is simple to operate; the obtained magnetotactic bacterial quantum dot microcapsule presents a typical core-shell structure, the inner core of the microcapsule is a single magnetic domain structure of magnetosome, and the shell of the microcapsule consists of uniform and compact CS/gamma-PGA/carbon quantum dots, so that the microcapsule shows good dispersibility and has better colloid stability; after 40 days, the detection is carried out again, the result is consistent with that before, and the stability is proved to be good.
(2) The single magnetic domain structure of the magnetosome is very stable at normal temperature, the release rate of the contained drug is low, and under the action of an alternating magnetic field (ACMF), the CS/gamma-PGA membrane structure and the permeability on the surface of the nanocrystal are changed based on the magnetocaloric effect of the inner core of the nanocrystal, so that the controllable release of the drug in the nanocrystal is promoted; by exerting the high magnetism and active targeting of the carrier, the carrier is fully enriched in organism tissues and generates heat alternately, thereby playing a role of thermal therapy; meanwhile, the heating can also promote the drug to be released into the tumor tissue and the sensitization of the drug molecules, thereby playing the role of chemotherapy.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments of the present invention, and it should be understood that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The invention provides a magnetotactic bacteria quantum dot microcapsule which has higher stability and targeting property and can be used for treating tumors in the field of biomedicine. Meanwhile, the invention also provides a preparation method of the magnetotactic bacteria quantum dot microcapsule, which is characterized in that chitosan oligosaccharide, gamma-polyglutamic acid, magnetosome and carbon quantum dots are compounded, and the method is simple to operate.
The magnetotactic bacteria quantum dot microcapsules of the present invention and the preparation method thereof are explained below.
The invention provides a magnetotactic bacteria quantum dot microcapsule, wherein the inner core of the microcapsule is magnetosome, and the surface of the magnetosome is coated with a uniform and compact mixture of chitosan oligosaccharide/gamma-polyglutamic acid/carbon quantum dots; the mass ratio of the magnetosome to the chitosan, the gamma-polyglutamic acid and the carbon quantum dots is (1: 1) - (3: 10) - (20): 1.
the particle size of the magnetotactic bacteria quantum dot microcapsule provided by the invention is less than 100 nm.
Furthermore, the molecular weight of the chitosan oligosaccharide is 1KD, the molecular weight of the gamma-polyglutamic acid is 40KD, and the carbon quantum dots are prepared by taking natural graphene as a raw material.
Further, the particle size of the magnetosome is 20-50 nm.
Furthermore, the particle size of the magnetotactic bacteria quantum dot microcapsule is 50-80nm, and the polydispersity is below 0.2.
Further, the loading drug is adriamycin.
The raw materials used in the invention are purchased from the market, the molecular weight of the chitosan oligosaccharide is 1KD, and the molecular weight of the gamma-polyglutamic acid is 40 KD.
The invention also provides a preparation method of the magnetotactic bacteria quantum dot microcapsule, which comprises the following steps:
step (1), adding 300mg of natural graphene into a mixed solution of 60mL of concentrated sulfuric acid and 20mL of concentrated nitric acid, performing ultrasonic treatment on the mixture for 2 hours to uniformly disperse the mixture, and then stirring and refluxing the mixture at 100 ℃ for 24 hours. The resulting dark brown solution was cooled to room temperature and diluted with deionized water to a total volume of about 800 mL. Sodium carbonate was then added to neutralize the remaining acid until the pH of the solution reached about 8. And concentrating the obtained solution by rotary evaporation, filtering a large amount of precipitated inorganic salts, and dialyzing the collected filtrate for four days by using a dialysis bag with the cut-off molecular weight of 8000-14000 to obtain the aqueous solution of the pure carbon quantum dots. Freezing and drying the aqueous solution of the carbon quantum dots to obtain carbon quantum dot solids, and re-dispersing the carbon quantum dot solids in the aqueous solution;
adding 1/3-2/3 amount of chitosan oligosaccharide into the aqueous solution, mixing, reacting for 1h at 95 ℃, performing ultrasonic treatment and centrifugation, performing ball milling treatment on large particles of chitosan oligosaccharide in liquid nitrogen, adding the rest of chitosan oligosaccharide, reacting for 1h at 60 ℃, performing freeze drying, dissolving in water again, adding magnetosomes, stirring for 30min, adding adriamycin, stirring uniformly, adding gamma-polyglutamic acid, and performing magnetic stirring for 12h to obtain microcapsules;
and (3) washing the composite microcapsule with absolute ethyl alcohol, carrying out magnet separation, and finally drying in vacuum at 60 ℃ to obtain the magnetotactic bacteria quantum dot microcapsule.
The mass and volume values used in the steps (1) to (3) are only illustrative, and those skilled in the art can modify the mass-volume ratio according to the teaching of the present invention, and the specific values in the steps should not be taken as a limitation to the scope of the present invention.
Further, in the step (1), the concentration of the carbon quantum dots in the aqueous solution is 0.2 mg/mL.
Further, in the step (2), the large-particle chitosan oligosaccharide is subjected to liquid nitrogen ball milling for 120-150 min until the particle size is 50-100 nm.
Further, in the step (2), the concentration of the chitosan oligosaccharide is 0.4 mg/mL.
Further, in the step (2), the concentration of the gamma-polyglutamic acid is 2 mg/mL.
Further, in the step (2), the magnetosome concentration is 0.2 mg/mL.
The invention mixes the magnetosome, the carbon quantum dots and the biological material to prepare the sustained-release microcapsule, and the microcapsule is used as an oral sustained-release preparation according to different treatment purposes, can also be used for preparing a targeted drug-loaded sustained-release preparation, can be applied to the field of biological medicine, and realizes magnetic fixation targeted sustained-release drug delivery.
The chitosan oligosaccharide utilized by the invention has the characteristics of bacteriostasis, no toxicity, good biocompatibility and the like; the gamma-polyglutamic acid has the characteristics of moisture retention, no toxicity, good biocompatibility and the like; the carbon quantum dots not only have the luminescent performance and the nano-size characteristic similar to those of the traditional quantum dots, but also have the characteristics of good water solubility, chemical inertness, easy functionalization, high photobleaching resistance, low toxicity, good biocompatibility and the like, the magnetosome particles are single magnetic domain crystals and have larger specific surface value, the particles are coated with a biological film, the cytotoxicity is not generated, the biocompatibility is good, the particles below 100nm are generated after the cross-linking reaction of the four substances, and the method is simple to operate. The obtained magnetotactic bacterial quantum dot microcapsule presents a typical core-shell structure, the inner core of the microcapsule is a single magnetic domain structure of magnetosome, and the shell of the microcapsule consists of uniform and compact CS/gamma-PGA/carbon quantum dots, so that the microcapsule shows good dispersibility and has better colloid stability; after 40 days, the detection is carried out again, the result is consistent with that before, and the stability is proved to be good.
The single magnetic domain structure of the magnetosome is very stable at normal temperature, the release rate of the contained drug is low, and under the action of an alternating magnetic field (ACMF), the CS/gamma-PGA membrane structure and the permeability on the surface of the nanocrystal are changed based on the magnetocaloric effect of the core of the nanocrystal, so that the controllable release of the drug in the nanocrystal is promoted. By exerting the high magnetism and active targeting of the carrier, the carrier is fully enriched in organism tissues and generates heat alternately, thereby playing the role of thermal therapy. Meanwhile, the heating can also promote the drug to be released into the tumor tissue and the sensitization of the drug molecules, thereby playing the role of chemotherapy. The composite carrier combines the action modes of magnetic thermal therapy and chemotherapy, the loaded medicine can effectively inhibit the growth of the tumor within a period of time, and the composite carrier has more prospect of clinical practical application than single thermal therapy or chemotherapy.
The preparation method of the magnetotactic bacteria quantum dot microcapsule of the present invention is described in detail with reference to the following specific examples.
Example 1
A preparation method of a magnetotactic bacteria quantum dot microcapsule comprises the following steps:
adding 300mg of natural graphene into a mixed solution of 60mL of concentrated sulfuric acid and 20mL of concentrated nitric acid, performing ultrasonic treatment on the mixture for 2 hours to uniformly disperse the mixture, and then stirring and refluxing the mixture for 24 hours at 100 ℃. The resulting dark brown solution was cooled to room temperature and diluted with deionized water to a total volume of about 800 mL. Sodium carbonate was then added to neutralize the remaining acid until the pH of the solution reached about 8. And concentrating the obtained solution by rotary evaporation, filtering a large amount of precipitated inorganic salts, and dialyzing the collected filtrate for four days by using a dialysis bag with the cut-off molecular weight of 8000-14000 to obtain the aqueous solution of the pure carbon quantum dots.
In the step (1), the aqueous solution of the carbon quantum dots is frozen and dried by suction to obtain carbon quantum dot solid, and the carbon quantum dot solid is dissolved in 10mL of water again, wherein the concentration is 0.2 mg/mL;
adding 1.5mg of chitosan oligosaccharide into the reaction system obtained in the step (1), mixing, reacting for 1h at 95 ℃, performing ultrasonic treatment for 10min, centrifuging, performing ball milling on large particles of chitosan oligosaccharide for 120min until the particle size is 50nm, adding 2.5mg of chitosan oligosaccharide, reacting for 1h at 60 ℃, freeze-drying for 12h, re-dissolving in 10mL of water, adding 2mg of magnetosome, stirring for 30min, adding 1mL of 5mg/mL adriamycin methanol solution, stirring uniformly, adding 20mg of gamma-polyglutamic acid, and stirring for 12h by magnetic force to obtain microcapsules;
and (3) washing the composite microcapsule with absolute ethyl alcohol, separating by using a magnet, and finally drying in vacuum at 60 ℃ to obtain the iridium nano intelligent composite medicament.
The iridium nanometer intelligent composite medicament prepared in the embodiment 1 has a particle size of 50-80nm through detection, and presents a typical core-shell structure, wherein the inner core is a single magnetic domain structure of a magnetosome, and the surface of the magnetosome is coated with a mixture (CS/gamma-PGA/carbon quantum dot) of uniform and compact chitosan oligosaccharide, gamma-polyglutamic acid and carbon quantum dot; the mass ratio of the magnetosome to the chitosan, the gamma-polyglutamic acid and the carbon quantum dots is 1:2:10:1, the dispersity is good, the polydispersity is below 0.2, and the colloidal stability is good;
the magnetotactic bacteria quantum dot microcapsule has the drug loading rate of 7.89 percent, the drug wrapping rate of 92.17 percent, the drug concentration reaching the effective concentration and being capable of being continuously released for 72 hours, and has good slow release performance. After 40 days, the detection result is consistent with that, and the stability is proved to be good.
Example 2:
a preparation method of a magnetotactic bacteria quantum dot microcapsule comprises the following steps:
adding 300mg of natural graphene into a mixed solution of 60mL of concentrated sulfuric acid and 20mL of concentrated nitric acid, performing ultrasonic treatment on the mixture for 2 hours to uniformly disperse the mixture, and then stirring and refluxing the mixture for 24 hours at 100 ℃. The resulting dark brown solution was cooled to room temperature and diluted with deionized water to a total volume of about 800 mL. Sodium carbonate was then added to neutralize the remaining acid until the pH of the solution reached about 8. And concentrating the obtained solution by rotary evaporation, filtering a large amount of precipitated inorganic salts, and dialyzing the collected filtrate for four days by using a dialysis bag with the cut-off molecular weight of 8000-14000 to obtain the aqueous solution of the pure carbon quantum dots. Freezing and drying the water solution of the carbon quantum dots to obtain carbon quantum dot solids, and dissolving the carbon quantum dot solids in 10mL of water again, wherein the concentration of the carbon quantum dot solids is 0.2 mg/mL;
adding 1mg of chitosan oligosaccharide into the reaction system obtained in the step (1), mixing, reacting for 1h at 95 ℃, performing ultrasonic treatment for 10min, centrifuging, performing ball milling on large particles of chitosan oligosaccharide for 120min until the particle size is 50nm, adding 2mg of chitosan oligosaccharide, reacting for 1h at 60 ℃, performing freeze drying for 12h, dissolving in 10mL of water again, adding 2mg of magnetosome, stirring for 30min, adding 1mL of 5mg/mL adriamycin methanol solution, uniformly stirring, adding 25mg of gamma-polyglutamic acid, and performing magnetic stirring for 12h to obtain microcapsules;
and (3) washing the composite microcapsule with absolute ethyl alcohol, separating by using a magnet, and finally drying in vacuum at 60 ℃ to obtain the iridium nano intelligent composite medicament.
The iridium nanometer intelligent composite medicament prepared in the embodiment 2 has a particle size of 50-80nm through detection, and presents a typical core-shell structure, wherein the inner core is a single magnetic domain structure of a magnetosome, and the surface of the magnetosome is coated with a mixture (CS/gamma-PGA/carbon quantum dot) of uniform and compact chitosan oligosaccharide, gamma-polyglutamic acid and carbon quantum dot; the mass ratio of the magnetosome to the chitosan, the gamma-polyglutamic acid and the carbon quantum dots is 2:3:25:2, the dispersity is good, the polydispersity is below 0.2, and the colloidal stability is good;
the magnetotactic bacteria quantum dot microcapsule has the drug loading rate of 5.43 percent, the drug wrapping rate of 87.96 percent, the drug concentration reaching the effective concentration and being capable of being continuously released for 72 hours, and has good slow release performance. After 40 days, the detection result is consistent with that, and the stability is proved to be good.
Example 3:
a preparation method of a magnetotactic bacteria quantum dot microcapsule comprises the following steps:
adding 300mg of natural graphene into a mixed solution of 60mL of concentrated sulfuric acid and 20mL of concentrated nitric acid, performing ultrasonic treatment on the mixture for 2 hours to uniformly disperse the mixture, and then stirring and refluxing the mixture for 24 hours at 100 ℃. The resulting dark brown solution was cooled to room temperature and diluted with deionized water to a total volume of about 800 mL. Sodium carbonate was then added to neutralize the remaining acid until the pH of the solution reached about 8. And concentrating the obtained solution by rotary evaporation, filtering a large amount of precipitated inorganic salts, and dialyzing the collected filtrate for four days by using a dialysis bag with the cut-off molecular weight of 8000-14000 to obtain the aqueous solution of the pure carbon quantum dots. Freezing and drying the water solution of the carbon quantum dots to obtain carbon quantum dot solids, and dissolving the carbon quantum dot solids in 10mL of water again, wherein the concentration of the carbon quantum dot solids is 0.2 mg/mL;
adding 2mg of chitosan oligosaccharide into the reaction system obtained in the step (1), mixing, reacting for 1h at 95 ℃, performing ultrasonic treatment for 10min, centrifuging, performing ball milling on large particles of chitosan oligosaccharide for 120min until the particle size is 50nm, adding 4mg of chitosan oligosaccharide, reacting for 1h at 60 ℃, performing freeze drying for 12h, dissolving in 10mL of water again, adding 2mg of magnetosome, stirring for 30min, adding 1mL of 5mg/mL adriamycin methanol solution, uniformly stirring, adding 30mg of gamma-polyglutamic acid, and performing magnetic stirring for 12h to obtain microcapsules;
and (3) washing the composite microcapsule with absolute ethyl alcohol, separating by using a magnet, and finally drying in vacuum at 60 ℃ to obtain the iridium nano intelligent composite medicament.
The iridium nanometer intelligent composite medicament prepared in the embodiment 3 has a particle size of 80-130nm through detection, and presents a typical core-shell structure, wherein the inner core is a single magnetic domain structure of a magnetosome, and the surface of the magnetosome is coated with a mixture (CS/gamma-PGA/carbon quantum dot) of uniform and compact chitosan oligosaccharide, gamma-polyglutamic acid and carbon quantum dot; the mass ratio of the magnetosome to the chitosan, the gamma-polyglutamic acid and the carbon quantum dots is 1:3:15:1, the dispersity is good, the polydispersity is below 0.2, and the colloidal stability is good;
the magnetotactic bacteria quantum dot microcapsule has the drug loading rate of 4.32 percent, the drug wrapping rate of 89.56 percent, the drug concentration reaching the effective concentration and being capable of being continuously released for 72 hours, and has good slow release performance. After 40 days, the detection result is consistent with that, and the stability is proved to be good.
Comparative example 1
The difference from the embodiment 1 is that: and (2) adding 4mg of chitosan oligosaccharide and 20mg of gamma-polyglutamic acid into the reaction system in the step (1), reacting for 2 hours at 95 ℃, and then removing large particles by ultrasonic and centrifugal treatment to obtain the magnetotactic bacteria quantum dot microcapsule.
The magnetotactic bacteria quantum dot microcapsule obtained in the comparative example 1 has the grain diameter of 90nm and the polydispersity coefficient of about 0.3 through detection, and has poorer colloid stability compared with a composite carrier; the drug concentration can reach the effective concentration and can be continuously released for 60 hours. After detection for 40 days, obvious aggregation phenomenon appears, and the stability of the magnetotactic bacteria quantum dot microcapsule is poorer than that of the magnetotactic bacteria quantum dot microcapsule in the example 1.
Comparative example 2
The difference from the embodiment 1 is that: and (2) adding 4mg of chitosan oligosaccharide and 20mg of gamma-polyglutamic acid into the reaction system in the step (1), reacting for 2 hours at 60 ℃, and then removing large particles by ultrasonic and centrifugal treatment to obtain the magnetotactic bacteria quantum dot microcapsule.
The magnetotactic bacteria quantum dot microcapsule obtained in the comparative example 2 has the grain diameter of 120nm and the polydispersity coefficient of about 0.3 through detection, and has poorer colloid stability compared with a composite carrier; the drug concentration can reach the effective concentration and can be continuously released for 60 hours. After detection for 40 days, obvious aggregation phenomenon appears, and the stability of the magnetotactic bacteria quantum dot microcapsule is poorer than that of the magnetotactic bacteria quantum dot microcapsule in the example 1.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (7)
1. A magnetotactic bacteria quantum dot microcapsule is characterized in that: the inner core of the microcapsule is a single magnetic domain structure of magnetosomes, and the surfaces of the magnetosomes are coated with a mixture of chitosan oligosaccharide, gamma-polyglutamic acid and carbon quantum dots; the mass ratio of the magnetosome to the chitosan, the gamma-polyglutamic acid and the carbon quantum dots is as follows:
magnetosome 1 weight part
1-3 parts of chitosan oligosaccharide
10-20 parts of gamma-polyglutamic acid
1 part by weight of carbon quantum dots;
the microcapsule has a particle diameter of 50 to 80nm and a polydispersity of 0.2 or less.
2. The magnetotactic bacterial quantum dot microcapsule of claim 1, wherein: the molecular weight of the chitosan oligosaccharide is 1KD, the molecular weight of the gamma-polyglutamic acid is 40KD, and the carbon quantum dots are prepared by taking natural graphene as a raw material.
3. The magnetotactic bacterial quantum dot microcapsule of claim 1, wherein: the particle size of the magnetosome is 20-50 nm.
4. The magnetotactic bacterial quantum dot microcapsule of claim 1, wherein: the load drug is adriamycin.
5. A preparation method of the magnetotactic bacteria quantum dot microcapsule as claimed in any one of claims 1 to 4, characterized by comprising the steps of:
adding natural graphene into a mixed solution of concentrated sulfuric acid and concentrated nitric acid, ultrasonically dispersing the mixture uniformly, and stirring and refluxing at 100 ℃; cooling the obtained brownish black solution to room temperature, and then adding deionized water for dilution; then adding sodium carbonate to neutralize the residual acid until the pH of the solution is 8; concentrating the obtained solution by rotary evaporation, filtering and removing precipitated inorganic salt, and dialyzing the collected filtrate by using a dialysis bag with the cut-off molecular weight of 8000-14000 to obtain an aqueous solution of pure carbon quantum dots; freezing and drying the aqueous solution of the carbon quantum dots to obtain carbon quantum dot solids, and dispersing the carbon quantum dot solids in the aqueous solution again;
adding 1/3-2/3 amount of chitosan oligosaccharide into the dispersion, mixing, reacting for 1h at 95 ℃, performing ultrasonic treatment and centrifugation, performing ball milling treatment on large particles of chitosan oligosaccharide in liquid nitrogen, adding the rest of chitosan oligosaccharide, reacting for 1h at 60 ℃, performing freeze drying, dissolving in water again, adding magnetosomes, stirring uniformly, adding gamma-polyglutamic acid, and performing magnetic stirring to obtain composite microcapsules;
and (3) washing the composite microcapsule with absolute ethyl alcohol, carrying out magnet separation, and finally drying in vacuum at 60 ℃ to obtain the magnetotactic bacteria quantum dot microcapsule.
6. The method according to claim 5, wherein the concentration of the carbon quantum dots in the aqueous solution is 0.2 mg/mL.
7. The method of claim 5, wherein: in the step (2), the large particles are subjected to ball milling for 120-150 min by using liquid nitrogen until the particle size is 50-100 nm.
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| CN109395086B (en) * | 2018-11-29 | 2022-02-01 | 曲阜师范大学 | Graphene oxide-based composite nano-drug carrier and preparation method thereof |
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