CN106581688A - Medicine carrier based on graphene and preparation method of same - Google Patents
Medicine carrier based on graphene and preparation method of same Download PDFInfo
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- CN106581688A CN106581688A CN201610981262.XA CN201610981262A CN106581688A CN 106581688 A CN106581688 A CN 106581688A CN 201610981262 A CN201610981262 A CN 201610981262A CN 106581688 A CN106581688 A CN 106581688A
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 title claims abstract description 91
- 229910021389 graphene Inorganic materials 0.000 title claims abstract description 88
- 239000003814 drug Substances 0.000 title claims abstract description 17
- 238000002360 preparation method Methods 0.000 title claims description 13
- 229940079593 drug Drugs 0.000 title description 9
- 229920001690 polydopamine Polymers 0.000 claims abstract description 32
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000000377 silicon dioxide Substances 0.000 claims abstract description 9
- 239000003937 drug carrier Substances 0.000 claims description 33
- 239000000243 solution Substances 0.000 claims description 12
- 239000007864 aqueous solution Substances 0.000 claims description 10
- CTENFNNZBMHDDG-UHFFFAOYSA-N Dopamine hydrochloride Chemical compound Cl.NCCC1=CC=C(O)C(O)=C1 CTENFNNZBMHDDG-UHFFFAOYSA-N 0.000 claims description 9
- 238000006243 chemical reaction Methods 0.000 claims description 9
- 229960001149 dopamine hydrochloride Drugs 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 239000003093 cationic surfactant Substances 0.000 claims description 6
- 150000001282 organosilanes Chemical class 0.000 claims description 6
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims description 5
- BOTDANWDWHJENH-UHFFFAOYSA-N Tetraethyl orthosilicate Chemical compound CCO[Si](OCC)(OCC)OCC BOTDANWDWHJENH-UHFFFAOYSA-N 0.000 claims description 5
- 239000007983 Tris buffer Substances 0.000 claims description 5
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 5
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 5
- 239000007853 buffer solution Substances 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- WYTZZXDRDKSJID-UHFFFAOYSA-N (3-aminopropyl)triethoxysilane Chemical compound CCO[Si](OCC)(OCC)CCCN WYTZZXDRDKSJID-UHFFFAOYSA-N 0.000 claims description 2
- UUEWCQRISZBELL-UHFFFAOYSA-N 3-trimethoxysilylpropane-1-thiol Chemical compound CO[Si](OC)(OC)CCCS UUEWCQRISZBELL-UHFFFAOYSA-N 0.000 claims description 2
- 229960002233 benzalkonium bromide Drugs 0.000 claims description 2
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 2
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 claims description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 2
- 125000002091 cationic group Chemical group 0.000 claims description 2
- WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 claims description 2
- 229960003638 dopamine Drugs 0.000 claims description 2
- 229920002401 polyacrylamide Polymers 0.000 claims description 2
- 238000005119 centrifugation Methods 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 13
- 230000004048 modification Effects 0.000 abstract description 10
- 238000012986 modification Methods 0.000 abstract description 10
- 238000010521 absorption reaction Methods 0.000 abstract description 5
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 abstract description 4
- 229910052710 silicon Inorganic materials 0.000 abstract description 4
- 239000010703 silicon Substances 0.000 abstract description 4
- 238000003384 imaging method Methods 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 235000012239 silicon dioxide Nutrition 0.000 abstract 2
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 239000002086 nanomaterial Substances 0.000 description 12
- 238000011068 loading method Methods 0.000 description 7
- 238000012360 testing method Methods 0.000 description 6
- 229920000547 conjugated polymer Polymers 0.000 description 5
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- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 229910000510 noble metal Inorganic materials 0.000 description 4
- 238000007626 photothermal therapy Methods 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 3
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- 239000011148 porous material Substances 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
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- 150000003384 small molecules Chemical class 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 239000011358 absorbing material Substances 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 229960004679 doxorubicin Drugs 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 238000001179 sorption measurement Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
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- 125000003118 aryl group Chemical group 0.000 description 1
- 238000004630 atomic force microscopy Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
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- 229910002804 graphite Inorganic materials 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 239000013335 mesoporous material Substances 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
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- 239000000178 monomer Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000000696 nitrogen adsorption--desorption isotherm Methods 0.000 description 1
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- 210000000056 organ Anatomy 0.000 description 1
- 239000011368 organic material Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000012221 photothermal agent Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 150000004032 porphyrins Chemical class 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000002210 silicon-based material Substances 0.000 description 1
- IZTQOLKUZKXIRV-YRVFCXMDSA-N sincalide Chemical compound C([C@@H](C(=O)N[C@@H](CCSC)C(=O)NCC(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](N)CC(O)=O)C1=CC=C(OS(O)(=O)=O)C=C1 IZTQOLKUZKXIRV-YRVFCXMDSA-N 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a medicine carrier based on graphene, wherein reduced graphene oxide is coated with polydopamine with surface modification by mesoporous silicon dioxide, thickness of a mesoporous silicon dioxide layer being 2-50 nm and thickness of a polydopamine layer being 1-30 nm. In the medicine carrier based on graphene, the reduced graphene oxide is coated with the polydopamine, so that biocompatibility is improved and photo-thermal absorption performance of the medicine carrier is improved. Through external modification of the mesoporous silicon layer on the reduced graphene oxide coated with polydopamine, the photo-thermal performance and photo-acoustic imaging performance of the material are improved, and supporting load of the medicine is also increased. Meanwhile, the silicon-base material is beneficial to multifunctional modification, so that the medicine carrier based on graphene can achieve multi-functions such as imaging, therapy and medicine supporting.
Description
Technical Field
The invention belongs to the field of biomedical materials, and particularly relates to a graphene material-based drug carrier and a preparation method thereof.
Background
The key to the successful realization of photothermal therapy is the selection of near infrared light absorbing materials with excellent properties. The light absorbing material not only requires a high absorption of near infrared light, but also converts the absorbed light energy into heat to be released. In addition, these materials must be biocompatible, have a suitable size, and can be enriched at the tumor site by active targeting. At present, a number of nanomaterials with strong absorption in the near infrared region are applied for photothermal therapy and validated at the cellular or living level. They mainly include inorganic nanomaterials such as noble metal nanomaterials, carbon-based nanomaterials, and other metal nanomaterials, and organic materials such as near-infrared dyes and conjugated polymers. After the temperature of the noble metal photo-thermal material rises, the shape of the noble metal photo-thermal material is easy to change, and the photo-thermal stability of the noble metal photo-thermal material is influenced; other metal nano materials are mainly semiconductor nano materials, and due to poor biological metabolism of metal nano ions, the metabolic pathway and toxicity of the metal nano ions in vivo need to be systematically examined and examined. In addition, the photo-thermal conversion efficiency of semiconductor nanoparticles is low, and although some methods for improving the photo-thermal conversion efficiency have been proposed, semiconductor nanoparticles having uniform morphology, stable size and good performance are often involved in high-temperature reactions. The simple application of organic small molecules in photothermal therapy has some inevitable problems, such as unstable optical properties under the action of heat, easy photobleaching, and the drug being discharged out of the body soon after intravenous administration. Researchers can make the small molecules and other macromolecules exist in an aggregate form to form nano micelles or vesicles, and the stability of the organic small molecules is effectively improved. However, such small organic molecules, such as ICG and porphyrin, are coated in the polymer by non-covalent bond means, or self-assembled to form nano aggregates, which are released to some extent under higher intensity laser irradiation and during the biological cycle, resulting in still poor stability. In addition to the photothermal materials described above, there is a class of dopamine black pigment photothermal agents that has recently attracted considerable attention from researchers. However, pure polydopamine is difficult to form into nano-materials, and higher drug loading cannot be obtained.
In the carbon-based nano material, the photo-thermal conversion efficiency of pure graphene oxide or reduced graphene oxide is not high, and the surface of the nano material is easy to adsorb protein, so that oxidative stress is generated, and the nano material has certain limitation when being used as a drug carrier.
Graphene is a planar thin film of hexagonal honeycomb lattice consisting of carbon atoms with sp2 hybridized orbitals, is only one carbon atom thick, and has many excellent physical and chemical properties. Graphene Oxide (GO), an intermediate product of graphene, is easier to modify because of containing a large amount of oxygen-containing functional groups, and is highly appreciated in the field of biological medicine. Due to the photothermal effect shown by the existence of a large number of conjugated structures in GO, GO can be used as a drug carrier for improving an additional synergistic therapeutic means after administration. However, graphene oxide without any surface modification has poor stability in physiological environment due to the surface charge effect and the characteristic of non-specific protein adsorption, and can cause damage to part of organs (such as lung) of animals. Moreover, GO is often loaded with drug molecules with aromatic ring structures efficiently through pi-pi stacking, so that the types and the drug loading amount of the drugs are limited. The functional modification and modification of GO to improve its performance is a prerequisite and key for the application of GO in the biological field.
Disclosure of Invention
The technical problem to be solved by the invention is to overcome the defects of the prior art and provide a graphene-based drug carrier.
The invention also aims to provide a preparation method of the graphene-based drug carrier.
The third purpose of the invention is to propose the application of the graphene-based drug carrier.
The technical scheme for realizing the above purpose of the invention is as follows:
a graphene-based drug carrier is reduced graphene oxide coated by polydopamine with surface modified mesoporous silica, wherein the thickness of a mesoporous silica layer is 2-50 nm, and the thickness of a polydopamine layer is 1-30 nm.
The polydopamine is used as an organic conjugated polymer with strong absorption in near infrared, and has good stability and biocompatibility in application of photothermal therapy. Conjugated polymers obtained by oxidative polymerization of monomers generally exhibit hydrophobicity and form aggregated nanoparticles in aqueous solutions, thereby affecting their use at the biological level. The invention uses mesoporous material to carry out surface chemical modification on the conjugated polymer, so that the conjugated polymer has good stability in physiological environment.
Preferably, the thickness of the mesoporous silica layer is 5-20 nm, the thickness of the dopamine layer is 3-20 nm, and the size of the coated reduced graphene oxide is 20-300 nm.
A preparation method of a graphene-based drug carrier comprises the following steps:
s1, dispersing graphene oxide in a buffer solution with the pH value of 8.0-9.0, adding dopamine hydrochloride, and reacting at 50-90 ℃ for 4-48 hours to obtain polydopamine-coated reduced graphene oxide;
s2, dispersing the polydopamine-coated reduced graphene oxide obtained in the step S1 in an aqueous solution, adding a cationic surfactant, adjusting the pH value to 10-12, adding organosilane, and reacting at room temperature for 12-36 hours to obtain the graphene-based drug carrier.
Further, in step S1, the graphene oxide has a size of 20 to 300nm, and the buffer solution with a pH value of 8.0 to 9.0 is a tris buffer solution.
In the step S1, the mass ratio of the graphene oxide to the dopamine hydrochloride is 1-3: 1; adding dopamine hydrochloride, and reacting at 60-70 ℃ for 12-24 hours.
In step S2, the cationic surfactant is selected from cetyl trimethyl ammonium bromide, cetyl trimethyl ammonium chloride, cationic polyacrylamide, benzalkonium chloride and benzalkonium bromide, and the concentration of the cationic surfactant in the aqueous solution is 0.002-0.2 mol/L.
In the step S2, the concentration of the polydopamine-coated reduced graphene oxide dispersed in the aqueous solution is 0.005-1 mg/mL, and the mass ratio of the organosilane to the polydopamine-coated reduced graphene oxide is 0.1-1.
In step S2, the organosilane is one or more of ethyl orthosilicate, 3-aminopropyl triethoxysilane, and gamma-mercaptopropyl trimethoxysilane.
Wherein,after the reaction of step S2, the product is washed with methanol and/or ethanol and centrifuged. With NaOH, Na2CO3、KOH、NaHCO3Adjusting the pH value.
The graphene-based drug carrier disclosed by the invention is applied to preparation of a photothermal treatment reagent.
The invention has the beneficial effects that:
the graphene-based drug carrier provided by the invention is coated with polydopamine outside the reduced graphite oxide, so that the biocompatibility is improved, and meanwhile, the photo-thermal absorption performance of the drug carrier can be improved. The photo-thermal conversion efficiency of pure graphene oxide or reduced graphene oxide is not high, and the surface of the graphene oxide or reduced graphene oxide is easy to adsorb protein, so that oxidative stress is generated, and the graphene oxide or reduced graphene oxide has certain limitation when being used as a drug carrier. The photo-thermal performance and photo-acoustic imaging performance of the material can be improved by coating and reducing the graphene oxide with polydopamine and then modifying the mesoporous silicon layer, and the drug loading capacity is improved.
Furthermore, the preparation method of the graphene-based drug carrier is simple, mild in reaction conditions and low in cost.
Drawings
Fig. 1 is a transmission electron micrograph of a graphene-based drug carrier according to example 2 of the present invention;
fig. 2 is a nitrogen adsorption desorption isotherm and a pore size distribution diagram of a graphene-based drug carrier in example 2 of the present invention;
FIG. 3 is a photothermal temperature profile of a graphene-based drug carrier in example 2 of the present invention;
fig. 4 is a graph of the relationship between the concentration and the cell viability of graphene oxide, polydopamine coated reduced graphene oxide and graphene-based drug carrier in example 2 of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.
Graphene oxide used in the examples was purchased from Nanjing Xiapong nanomaterial science and technology, Inc.
The materials in the examples are prepared according to known methods or are directly commercially available, unless otherwise specified.
Experimental example 1:
10mL of graphene oxide (2mg/mL of aqueous dispersion) and 10mg of dopamine hydrochloride are mixed, 0.1mL of 1M tris buffer solution is added, and the mixture reacts for 24 hours at 60 ℃ to obtain polydopamine-coated reduced graphene oxide, which is recorded as pRGO. The thickness of the polydopamine layer was observed to be within 10nm by atomic force microscopy.
0.8mL of 0.2M hexadecyl trimethyl ammonium bromide solution, 0.18mL of NaOH (0.1mol/L) is added to adjust the pH value of the solution to 11, 0.06mL of ethyl orthosilicate is added to react for 24 hours, and the thickness of the obtained mesoporous silicon material is 5-10 nm.
Example 2: preparation of graphene-based drug carriers
Mixing 10mL of graphene oxide (2mg/mL) water dispersion and 10mg of dopamine hydrochloride, adding 0.1mL of 1mol/L tris buffer solution, and reacting at 60 ℃ for 24 hours to obtain polydopamine-coated reduced graphene oxide;
dispersing 0.1mg of the obtained polydopamine-coated reduced graphene oxide in 20mL of aqueous solution, wherein the concentration is 0.005mg/mL, adding 0.8mL of 0.2M hexadecyl trimethyl ammonium bromide solution, and then adding 0.18mL of NaOH (0.1mol/L), so that the pH value of the solution is 11; 0.06mL of ethyl orthosilicate was added and the reaction was carried out for 24 hours. And centrifugally washing with ethanol and water to obtain the graphene-based drug carrier.
Example 3: preparation of graphene-based drug carriers
Mixing 10mL of graphene oxide (1mg/mL) and 10mg of dopamine hydrochloride, adding 0.1mL of 1mol/L tris buffer solution, and reacting at 90 ℃ for 12 hours to obtain polydopamine-coated reduced graphene oxide;
and dispersing 0.1mg of the obtained polydopamine-coated reduced graphene oxide in 20mL of aqueous solution, adding 0.005mg/mL of 0.8mL of 0.2mol/L cetyl trimethyl ammonium bromide solution, then adding 0.18mL of NaOH (0.1M), adding 0.1mL of ethyl orthosilicate, reacting for 24h, and carrying out centrifugal washing to obtain the graphene-based drug carrier.
Fig. 1 is a scanning electron microscope image of the graphene-based drug carrier of the present embodiment, in which an obvious mesoporous structure can be seen; FIG. 2 is the nitrogen adsorption and desorption isotherm and pore size distribution curve, and it can be seen that the specific surface area reaches 1154m2(ii)/g, pore diameter is 3.82 nm.
Test example 1 photothermal Effect test
Reduced graphene oxide pRGO is respectively irradiated by near infrared light, the mesoporous silica coated reduced graphene oxide pRGO @ MS prepared in example 2, graphene oxide GO and phosphate buffer PBS are used as controls.
Fig. 3 is a photo-thermal curve of graphene oxide, poly-dopamine coated reduced graphene oxide pRGO, and the drug carrier pRGO @ MS for graphene prepared in example 2, and it can be seen that after poly-dopamine modification, the photo-thermal effect of the material is improved remarkably, and the photo-thermal effect of the modified mesoporous silicon layer is not greatly affected.
Test example 2 drug-loading test
The method comprises the steps of loading doxorubicin by graphene oxide GO, reduced graphene oxide RGO, polydopamine-coated reduced graphene oxide pRGO and the graphene-based drug carriers prepared in examples 1 and 2, namely putting the carriers into an aqueous solution (2mg/mL) of the doxorubicin, stirring overnight, and centrifuging and washing to remove the unloaded drug. The drug loading rates are calculated to be 40mg/mg, 22mg/mg, 78mg/mg, 144mg/mg and 145mg/mg respectively. The result shows that the modification of the polydopamine layer and the modification of the mesoporous silicon layer play a great role in improving the drug-loading capacity, and simultaneously, the photo-thermal property is greatly improved, so that the material per se has an application significance in drug carriers.
Test example 3 toxicity evaluation test
Graphene oxide GO, a polydopamine-coated reduced graphene oxide pRGO prepared in experiment example 1 after reacting for 24 hours, and a graphene-based drug carrier pRGO @ MS prepared in example 2 are subjected to toxicity evaluation by using a CCK-8 kit, and the results are shown in FIG. 4.
The above examples are only for describing the preferred embodiments of the present invention, and are not intended to limit the scope of the present invention, and various modifications and improvements made to the technical solution of the present invention by those skilled in the art without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.
Claims (10)
1. A drug carrier based on graphene is characterized in that,
the graphene oxide is reduced graphene oxide coated by polydopamine with surface modified mesoporous silica, wherein the thickness of a mesoporous silica layer is 2-50 nm, and the thickness of a polydopamine layer is 1-30 nm.
2. The graphene-based drug carrier according to claim 1, wherein the mesoporous silica layer has a thickness of 5 to 20nm, the dopamine layer has a thickness of 3 to 20nm, and the reduced graphene oxide has a size of 20 to 300 nm.
3. A preparation method of a graphene-based drug carrier is characterized by comprising the following steps:
s1, dispersing graphene oxide in a buffer solution with the pH value of 8.0-9.0, adding dopamine hydrochloride, and reacting at 50-90 ℃ for 4-48 hours to obtain polydopamine-coated reduced graphene oxide;
s2, dispersing the polydopamine-coated reduced graphene oxide obtained in the step S1 in an aqueous solution, adding a cationic surfactant, adjusting the pH value to 10-12, adding organosilane, and reacting at room temperature for 12-36 hours to obtain the graphene-based drug carrier.
4. The preparation method according to claim 3, wherein in step S1, the graphene oxide has a size of 20 to 300nm, and the buffer solution with a pH value of 8.0 to 9.0 is a tris buffer solution.
5. The preparation method according to claim 3, wherein in the step S1, the mass ratio of graphene oxide to dopamine hydrochloride is 1-3: 1; adding dopamine hydrochloride, and reacting at 60-70 ℃ for 12-24 hours.
6. The method according to claim 3, wherein in step S2, the cationic surfactant is selected from the group consisting of cetyltrimethyl ammonium bromide, cetyltrimethyl ammonium chloride, cationic polyacrylamide, benzalkonium chloride, and benzalkonium bromide, and the concentration of the cationic surfactant in the aqueous solution is 0.002-0.2 mol/L.
7. The method according to claim 3, wherein in step S2, the concentration of the polydopamine-coated reduced graphene oxide dispersed in the aqueous solution is 0.005-1 mg/mL, and the mass ratio of the organosilane to the polydopamine-coated reduced graphene oxide is 0.1-1.
8. The method of claim 3, wherein in step S2, the organosilane is one or more selected from the group consisting of ethyl orthosilicate, 3-aminopropyltriethoxysilane, and gamma-mercaptopropyltrimethoxysilane.
9. The method according to claim 3, wherein the reaction of step S2 is followed by washing the product with methanol and/or ethanol and centrifugation.
10. Use of a graphene-based pharmaceutical carrier according to claim 1 or 2 for the preparation of a photothermal therapeutic agent.
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