CN106581688A - Medicine carrier based on graphene and preparation method of same - Google Patents

Medicine carrier based on graphene and preparation method of same Download PDF

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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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graphene oxide
polydopamine
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graphene
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吴雁
邵磊厚
张瑞锐
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National Center for Nanosccience and Technology China
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34Macromolecular 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704Compounds 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K41/00Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
    • A61K41/0052Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy

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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

一种基于石墨烯的药物载体及其制备方法A kind of graphene-based drug carrier and preparation method thereof

技术领域technical field

本发明属于生物医药材料领域,具体涉及一种以基于石墨烯材料的药物载体及其制备的方法。The invention belongs to the field of biomedical materials, and in particular relates to a graphene-based drug carrier and a preparation method thereof.

背景技术Background technique

光热治疗可以成功实现的关键是选择性能优异的近红外光吸收材料。光吸收材料不仅要求对近红外光有高强吸收,并且需要将吸收的光能转化成热量释放出来的。此外,这些材料必须具备良好的生物相容性,拥有适当的尺寸,可通过主动靶向在肿瘤部位富集。目前,诸多在近红外区有强吸收的纳米材料被应用于光热治疗,并在细胞或活体水平上进行验证。它们主要包括无机纳米材料如贵金属纳米材料、碳基纳米材料和其他金属纳米材料,以及有机材料如近红外染料和共轭高分子等。贵金属光热材料在温度升高后,形貌易发生变化,影响其光热稳定性;其他金属纳米材料主要为半导体纳米材料,由于金属纳米离子的生物代谢差,对其在体内的代谢途径和毒性还需要系统的考察和检验。另外,半导体纳米颗粒的光热转换效率较低,虽然已经提出了一些提高其光热转换效率的方法,但得到均匀形貌,稳定尺寸,性能好的半导体纳米颗粒往往涉及高温反应。单纯的有机小分子应用于光热治疗存在着一些不可避免的问题,如热作用下其光学性质不稳定、易发生光漂白以及通过静脉给药之后药物很快会被排出体外等。研究者据此将这类小分子与其他高分子以聚集体形式存在形成纳米胶束或者囊泡,有效地提高有机小分子的稳定性。但是,这种有机小分子,如ICG、卟啉都是通过非共价键手段包覆在高分子内,或者自组装形成纳米聚集体,在较高强度激光照射下以及生物循环过程中或多或少的有一定的释放,导致稳定性仍然不高。除上述光热材料以外,还有一类多巴胺黑色素光热试剂最近引起了研究者的广泛关注。然而,单纯的聚多巴胺难以形成纳米材料,也无法获取更高的载药量。The key to the successful realization of photothermal therapy is the selection of near-infrared light-absorbing materials with excellent performance. Light-absorbing materials not only require high-intensity absorption of near-infrared light, but also need to convert the absorbed light energy into heat and release it. In addition, these materials must be biocompatible and of appropriate size for enrichment at the tumor site through active targeting. At present, many nanomaterials with strong absorption in the near-infrared region have been applied in photothermal therapy and verified at the level of cells or living bodies. They mainly include inorganic nanomaterials such as noble metal nanomaterials, carbon-based nanomaterials, and other metal nanomaterials, as well as organic materials such as near-infrared dyes and conjugated polymers. The shape of noble metal photothermal materials is easy to change after the temperature rises, which affects its photothermal stability; other metal nanomaterials are mainly semiconductor nanomaterials. Due to the poor biological metabolism of metal nanoions, the metabolic pathways and Toxicity also requires systematic investigation and testing. In addition, the light-to-heat conversion efficiency of semiconductor nanoparticles is low. Although some methods to improve the light-to-heat conversion efficiency have been proposed, obtaining semiconductor nanoparticles with uniform shape, stable size and good performance often involves high-temperature reactions. There are some unavoidable problems in the application of simple organic small molecules in photothermal therapy, such as their optical properties are unstable under the action of heat, they are prone to photobleaching, and the drugs will be excreted quickly after intravenous administration. Based on this, researchers combine these small molecules with other macromolecules in the form of aggregates to form nanomicelles or vesicles, which can effectively improve the stability of small organic molecules. However, such small organic molecules, such as ICG and porphyrin, are encapsulated in polymers by means of non-covalent bonds, or self-assembled to form nano-aggregates, which are more likely to occur under relatively high-intensity laser irradiation and during biological cycles. Or less certain release, resulting in the stability is still not high. In addition to the above-mentioned photothermal materials, there is also a class of dopamine melanin photothermal reagents that have recently attracted extensive attention from researchers. However, pure polydopamine is difficult to form nanomaterials and cannot obtain higher drug loading.

碳基纳米材料中,单纯的氧化石墨烯或者还原氧化石墨烯的光热转换效率不高,而且表面容易吸附蛋白,导致氧化应激产生,作为药物载体具有一定的局限性。Among carbon-based nanomaterials, simple graphene oxide or reduced graphene oxide has low photothermal conversion efficiency, and the surface is easy to adsorb proteins, resulting in oxidative stress, which has certain limitations as a drug carrier.

石墨烯是一种由碳原子以sp2杂化轨道组成的六角形呈蜂巢晶格的平面薄膜,只有一个碳原子厚度,具有很多优异的物理性质和化学性质。石墨烯的中间产物—氧化石墨烯(GO)因含有大量含氧官能团而更易于修饰,在生物医药领域备受推崇。由于GO中存在大量共轭结构而表现出的光热效应,使GO可作为一种给药后提高额外协同治疗手段的药物载体。然而,未经任何表面修饰的氧化石墨烯,由于表面电荷作用和非特异性吸附蛋白的特点,在生理环境下稳定性较差,会对动物部分器官(例如:肺)造成伤害。而且,GO载药往往是通过π-π堆垛作用高效装载具有芳香环结构的药物分子,因此对药物的种类以及载药量均有所限制。对GO进行功能化修饰和改性以改善其性能,是GO在生物领域应用的前提和关键。Graphene is a flat film of hexagonal honeycomb lattice composed of carbon atoms with sp2 hybrid orbitals. It is only one carbon atom thick and has many excellent physical and chemical properties. The intermediate product of graphene—graphene oxide (GO) is easier to modify due to its large number of oxygen-containing functional groups, and is highly respected in the field of biomedicine. Due to the photothermal effect exhibited by the presence of a large number of conjugated structures in GO, GO can be used as a drug carrier to enhance additional synergistic therapeutic means after administration. However, graphene oxide without any surface modification has poor stability in physiological environment due to surface charge effect and non-specific adsorption protein characteristics, which will cause damage to some organs of animals (such as lungs). Moreover, GO drug loading often efficiently loads drug molecules with aromatic ring structures through π-π stacking, so the type of drug and the amount of drug loaded are limited. Functional modification and modification of GO to improve its performance is the premise and key to the application of GO in the biological field.

发明内容Contents of the invention

本发明所要解决的技术问题在于克服现有技术的缺陷,提供一种基于石墨烯的药物载体。The technical problem to be solved by the present invention is to overcome the defects of the prior art and provide a graphene-based drug carrier.

本发明的另一目的是提出所述基于石墨烯的药物载体的制备方法。Another object of the present invention is to propose a preparation method of the graphene-based drug carrier.

本发明的第三个目的是提出所述基于石墨烯的药物载体的应用。The third object of the present invention is to propose the application of the graphene-based drug carrier.

实现本发明上述目的的技术方案为:The technical scheme that realizes the above-mentioned purpose of the present invention is:

一种基于石墨烯的药物载体,为表面修饰介孔二氧化硅的聚多巴胺所包覆的还原氧化石墨烯,其中,介孔二氧化硅层的厚度为2~50nm,聚多巴胺层的厚度为1~30nm。A graphene-based drug carrier, which is reduced graphene oxide coated by polydopamine surface-modified mesoporous silica, wherein the thickness of the mesoporous silica layer is 2-50 nm, and the thickness of the polydopamine layer is 1~30nm.

聚多巴胺作为在近红外有较强吸收的有机共轭高分子,在光热治疗的应用中具有良好的稳定性和生物相容性。采用单体氧化聚合的方式获得的共轭高分子通常呈现出疏水性,并且会在水溶液中形成聚集的纳米颗粒从而影响到其在生物水平的应用。本发明用介孔材料对这类共轭高分子进行表面化学修饰,使其在生理环境中具有良好的稳定性。As an organic conjugated polymer with strong absorption in the near infrared, polydopamine has good stability and biocompatibility in the application of photothermal therapy. Conjugated polymers obtained by oxidative polymerization of monomers are usually hydrophobic, and will form aggregated nanoparticles in aqueous solution, which will affect their application at the biological level. The present invention uses the mesoporous material to chemically modify the surface of the conjugated macromolecule so that it has good stability in the physiological environment.

优选地,所述介孔二氧化硅层的厚度为5~20nm,多巴胺层的厚度为3~20nm,被包覆的还原氧化石墨烯的尺寸为20~300nm。Preferably, the thickness of the mesoporous silicon dioxide 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.

一种基于石墨烯的药物载体的制备方法,包括步骤:A preparation method of a graphene-based drug carrier, comprising the steps of:

S1将氧化石墨烯分散在pH值为8.0~9.0的缓冲溶液中,再加入多巴胺盐酸盐,50~90℃反应4~48小时,得聚多巴胺包覆还原氧化石墨烯;S1 Disperse graphene oxide in a buffer solution with a pH value of 8.0-9.0, then add dopamine hydrochloride, and react at 50-90°C for 4-48 hours to obtain polydopamine-coated reduced graphene oxide;

S2将步骤S1所得聚多巴胺包覆还原氧化石墨烯分散在水溶液中,加入阳离子表面活性剂,调节pH值为10~12,加入有机硅烷,室温反应12~36小时,获得基于石墨烯的药物载体。S2 Disperse the polydopamine-coated reduced graphene oxide obtained in step S1 in an aqueous solution, add a cationic surfactant, adjust the pH value to 10-12, add organosilane, and react at room temperature for 12-36 hours to obtain a graphene-based drug carrier .

进一步地,步骤S1中,所述氧化石墨烯的尺寸为20~300nm,所述pH值为8.0~9.0的缓冲溶液为tris缓冲溶液。Further, in step S1, the size of the graphene oxide is 20-300 nm, and the buffer solution with a pH value of 8.0-9.0 is a tris buffer solution.

其中,步骤S1中,氧化石墨烯与多巴胺盐酸盐的质量比为1~3:1;加入多巴胺盐酸盐后60~70℃反应12~24小时。Wherein, in step S1, the mass ratio of graphene oxide to dopamine hydrochloride is 1-3:1; after adding dopamine hydrochloride, react at 60-70° C. for 12-24 hours.

其中,步骤S2中,所述阳离子表面活性剂选自十六烷基三甲基溴化铵、十六烷基三甲基氯化铵、阳离子聚丙烯酰胺、苯扎氯铵、苯扎溴铵,阳离子表面活性剂在水溶液中的浓度为0.002~0.2mol/L。Wherein, in step S2, the cationic surfactant is selected from cetyltrimethylammonium bromide, cetyltrimethylammonium chloride, cationic polyacrylamide, benzalkonium chloride, benzalkonium bromide , the concentration of the cationic surfactant in the aqueous solution is 0.002-0.2mol/L.

其中,步骤S2中,所述聚多巴胺包覆还原氧化石墨烯分散在水溶液中的浓度为0.005~1mg/mL,所述有机硅烷与聚多巴胺包覆还原氧化石墨烯的质量比为0.1~1。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.

其中,步骤S2中,所述有机硅烷为正硅酸乙酯、3-氨丙基三乙氧基硅烷、γ-巯丙基三甲氧基硅烷中的一种或多种。Wherein, in step S2, the organosilane is one or more of ethyl orthosilicate, 3-aminopropyltriethoxysilane, and γ-mercaptopropyltrimethoxysilane.

其中,步骤S2反应后用甲醇和/或乙醇洗涤产物、离心分离。用NaOH、Na2CO3、KOH、NaHCO3中的一种或多种调节pH值。Wherein, after the reaction in step S2, the product is washed with methanol and/or ethanol and centrifuged. Use one or more of NaOH, Na 2 CO 3 , KOH, NaHCO 3 to adjust the pH value.

本发明所述的基于石墨烯的药物载体在制备光热治疗试剂中的应用。Application of the graphene-based drug carrier of the present invention in the preparation of photothermal therapy reagents.

本发明的有益效果在于:The beneficial effects of the present invention are:

本发明提供的基于石墨烯的药物载体,在还原氧化石墨外包覆聚多巴胺,提高生物相容性的同时可以提高药物载体的光热吸收性能。单纯的氧化石墨烯或者还原氧化石墨烯的光热转换效率不高,而且表面容易吸附蛋白,导致氧化应激产生,作为药物载体具有一定的局限性。通过聚多巴胺包覆还原氧化石墨烯外部再修饰介孔硅层可以提高此类材料的光热性能和光声成像性能,以及提高药物负载量,同时硅基材料有利于多功能化修饰,使该基于石墨烯的药物载体可以实现成像和治疗以及负载药物的多种功能。The graphene-based drug carrier provided by the present invention is coated with polydopamine on the outside of the reduced graphite oxide, thereby improving the biocompatibility and improving the photothermal absorption performance of the drug carrier. The photothermal conversion efficiency of pure graphene oxide or reduced graphene oxide is not high, and the surface is easy to adsorb protein, resulting in oxidative stress, which has certain limitations as a drug carrier. Modification of the mesoporous silicon layer on the outside of reduced graphene oxide coated with polydopamine can improve the photothermal performance and photoacoustic imaging performance of such materials, as well as increase the drug loading capacity. At the same time, silicon-based materials are conducive to multifunctional modification, making this based Graphene drug carriers can realize multiple functions of imaging and therapy as well as loading drugs.

进一步地,该基于石墨烯的药物载体的制备方法简单,反应条件温和,成本低。Further, the preparation method of the graphene-based drug carrier is simple, the reaction conditions are mild, and the cost is low.

附图说明Description of drawings

图1是本发明实施例2基于石墨烯的药物载体的透射电镜图;Fig. 1 is the transmission electron micrograph of the drug carrier based on graphene of embodiment 2 of the present invention;

图2是本发明实施例2基于石墨烯的药物载体的氮气吸附脱附等温线和孔径分布图;Fig. 2 is the nitrogen adsorption-desorption isotherm and the pore size distribution figure of the drug carrier based on graphene in Example 2 of the present invention;

图3是本发明实施例2基于石墨烯的药物载体的光热升温曲线;Fig. 3 is the photothermal heating curve of the drug carrier based on graphene in Example 2 of the present invention;

图4是本发明实施例2氧化石墨烯、聚多巴胺包覆还原氧化石墨烯和基于石墨烯的药物载体的浓度和细胞存活率关系图。4 is a diagram showing the relationship between the concentration of graphene oxide, polydopamine-coated reduced graphene oxide, and graphene-based drug carrier and cell survival rate in Example 2 of the present invention.

具体实施方式detailed description

为了使本发明的目的、技术方案及优点更加清楚明白,以下结合附图及实施例,对本发明进行进一步详细说明。应当理解,此处所描述的具体实施例仅仅用以解释本发明,并不用于限定本发明。In order to make the object, technical solution and advantages of the present invention clearer, the present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described here are only used to explain the present invention, not to limit the present invention.

实施例中使用的氧化石墨烯购自南京先丰纳米材料科技有限公司。The graphene oxide used in the examples was purchased from Nanjing Xianfeng Nano Material Technology Co., Ltd.

如无特别说明,实施例中的材料为根据现有方法制备而得,或直接从市场上购得。Unless otherwise specified, the materials in the examples were prepared according to existing methods, or were directly purchased from the market.

实验例1:Experimental example 1:

将10mL氧化石墨烯(2mg/mL的水分散液)和10mg多巴胺盐酸盐混合,加入0.1mL 1M的tris缓冲溶液,60℃反应24小时,得聚多巴胺包覆还原氧化石墨烯,记为pRGO。通过原子力显微镜观察到聚多巴胺层的厚度在10nm以内。Mix 10mL graphene oxide (2mg/mL aqueous dispersion) and 10mg dopamine hydrochloride, add 0.1mL 1M tris buffer solution, and react at 60°C for 24 hours to obtain polydopamine-coated reduced graphene oxide, denoted as pRGO . The thickness of the polydopamine layer was observed by atomic force microscopy within 10 nm.

0.8mL 0.2M的十六烷基三甲基溴化铵溶液,再加入0.18mL的NaOH(0.1mol/L),使溶液的pH值为11,加入0.06mL正硅酸乙酯,反应24h,得到的介孔硅材料的厚度为5~10nm。0.8mL 0.2M cetyltrimethylammonium bromide solution, then add 0.18mL NaOH (0.1mol/L) to make the pH of the solution 11, add 0.06mL tetraethyl orthosilicate, react for 24h, The obtained mesoporous silicon material has a thickness of 5-10 nm.

实施例2:基于石墨烯的药物载体的制备Embodiment 2: Preparation of graphene-based drug carrier

将10mL氧化石墨烯(2mg/mL)水分散液和10mg多巴胺盐酸盐混合,加入0.1mL1mol/L的tris缓冲溶液,60℃反应24小时,得聚多巴胺包覆还原氧化石墨烯;Mix 10 mL of graphene oxide (2 mg/mL) aqueous dispersion and 10 mg of dopamine hydrochloride, add 0.1 mL of 1 mol/L tris buffer solution, and react at 60 ° C for 24 hours to obtain polydopamine-coated reduced graphene oxide;

将所得聚多巴胺包覆还原氧化石墨烯0.1mg分散在20mL水溶液中,浓度为0.005mg/mL,加入0.8mL 0.2M的十六烷基三甲基溴化铵溶液,再加入0.18mL的NaOH(0.1mol/L),使溶液的pH值为11;加入0.06mL正硅酸乙酯,反应24h。用乙醇和水离心洗涤,获得基于石墨烯的药物载体。The obtained polydopamine-coated reduced graphene oxide 0.1mg was dispersed in 20mL aqueous solution, the concentration was 0.005mg/mL, 0.8mL of 0.2M cetyltrimethylammonium bromide solution was added, and then 0.18mL of NaOH ( 0.1mol/L) to make the pH of the solution 11; add 0.06mL tetraethyl orthosilicate and react for 24h. After centrifugation and washing with ethanol and water, graphene-based drug carriers were obtained.

实施例3:基于石墨烯的药物载体的制备Embodiment 3: Preparation of graphene-based drug carrier

将10mL氧化石墨烯(1mg/mL)和10mg多巴胺盐酸盐混合,加入0.1mL 1mol/L的tris缓冲溶液,90℃反应12小时,得聚多巴胺包覆的还原氧化石墨烯;Mix 10 mL of graphene oxide (1 mg/mL) and 10 mg of dopamine hydrochloride, add 0.1 mL of 1 mol/L tris buffer solution, and react at 90°C for 12 hours to obtain polydopamine-coated reduced graphene oxide;

将所得聚多巴胺包覆还原氧化石墨烯0.1mg分散在20mL水溶液中,浓度为0.005mg/mL,0.8mL 0.2mol/L的十六烷基三甲基溴化铵溶液,再加入0.18mL的NaOH(0.1M),加入0.1mL正硅酸乙酯,反应24h,离心洗涤,获得所述基于石墨烯的药物载体。Disperse 0.1 mg of the obtained polydopamine-coated reduced graphene oxide in 20 mL of aqueous solution, the concentration is 0.005 mg/mL, 0.8 mL of 0.2 mol/L cetyltrimethylammonium bromide solution, and then add 0.18 mL of NaOH (0.1M), add 0.1mL tetraethyl orthosilicate, react for 24h, centrifuge and wash to obtain the graphene-based drug carrier.

图1为本实施例的基于石墨烯的药物载体的扫描电镜图,可看到明显的介孔结构;图2是其氮气吸附脱附等温线和孔径分布曲线,从图中可以看出其比表面积达到1154m2/g,孔径为3.82nm。Fig. 1 is the scanning electron micrograph of the drug carrier based on graphene of the present embodiment, can see obvious mesoporous structure; Fig. 2 is its nitrogen adsorption-desorption isotherm and pore size distribution curve, can find out its ratio from the figure The surface area reaches 1154m 2 /g, and the pore diameter is 3.82nm.

试验例1 光热效应试验Test Example 1 Photothermal effect test

用近红外光分别照射还原氧化石墨烯pRGO,实施例2制介孔二氧化硅包覆还原氧化石墨烯pRGO@MS,氧化石墨烯GO,磷酸缓冲液PBS为对照。The reduced graphene oxide pRGO, the mesoporous silica-coated reduced graphene oxide pRGO@MS prepared in Example 2, the graphene oxide GO, and the phosphate buffer PBS were respectively irradiated with near-infrared light.

图3为氧化石墨烯,聚多巴胺包覆还原氧化石墨烯pRGO,实施例2制石墨烯的药物载体pRGO@MS的光热曲线,可以看出,聚多巴胺修饰后,材料的光热效应提高非常明显,修饰介孔硅层后对其光热效果影响不大。Figure 3 is the photothermal curve of graphene oxide, polydopamine-coated reduced graphene oxide pRGO, and the graphene drug carrier pRGO@MS prepared in Example 2. It can be seen that the photothermal effect of the material is significantly improved after polydopamine modification , the modified mesoporous silicon layer has little effect on its photothermal effect.

试验例2 负载药物试验Test Example 2 Loading drug test

将氧化石墨烯GO、还原氧化石墨烯RGO、聚多巴胺包覆还原氧化石墨烯pRGO、实施例1和实施例2制基于石墨烯的药物载体对阿霉素进行负载,即将载体放入到阿霉素的水溶液(2mg/mL)中,搅拌过夜,离心洗涤去除未负载的药物。计算其载药量分别为40mg/mg,22mg/mg,78mg/mg,144mg/mg,145mg/mg。结果表明聚多巴胺层的修饰和介孔硅层的修饰在提高载药量上起到了巨大的作用,同时大大也提高了光热性能,赋予材料本身在药物载体上应用意义。Graphene oxide GO, reduced graphene oxide RGO, polydopamine-coated reduced graphene oxide pRGO, and the graphene-based drug carrier prepared in Example 1 and Example 2 are loaded on doxorubicin, that is, the carrier is put into the doxorubicin In an aqueous solution (2 mg/mL) of the drug, stirred overnight, centrifuged and washed to remove unloaded drug. The calculated drug loads are 40mg/mg, 22mg/mg, 78mg/mg, 144mg/mg, 145mg/mg respectively. The results show that the modification of the polydopamine layer and the modification of the mesoporous silicon layer have played a huge role in increasing the drug loading capacity, and at the same time greatly improved the photothermal performance, endowing the material itself with significance in the application of drug carriers.

试验例3 毒性评价试验Test Example 3 Toxicity Evaluation Test

对氧化石墨烯GO、实验例1反应24小时制聚多巴胺包覆还原氧化石墨烯pRGO、实施例2制基于石墨烯的药物载体pRGO@MS,用CCK-8试剂盒进行毒性评价,结果如图4所示,聚多巴胺和介孔硅的修饰降低了氧化石墨烯的毒性,提高了其生物相容性。Toxicity evaluation of graphene oxide GO, polydopamine-coated reduced graphene oxide pRGO prepared by reacting for 24 hours in Experimental Example 1, and graphene-based drug carrier pRGO@MS prepared in Example 2 was performed with the CCK-8 kit, and the results are shown in the figure 4, the modification of polydopamine and mesoporous silicon reduces the toxicity of graphene oxide and improves its biocompatibility.

以上的实施例仅仅是对本发明的优选实施方式进行描述,并非对本发明的范围进行限定,在不脱离本发明设计精神的前提下,本领域普通工程技术人员对本发明的技术方案作出的各种变型和改进,均应落入本发明的权利要求书确定的保护范围内。The above embodiments are only descriptions of preferred implementations of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, ordinary engineers and technicians in the field may make various modifications to the technical solutions of the present invention. and improvements, all should fall within the scope of protection determined by the claims of the present invention.

Claims (10)

1.一种基于石墨烯的药物载体,其特征在于,1. A drug carrier based on graphene, characterized in that, 为表面修饰介孔二氧化硅的聚多巴胺所包覆还原氧化石墨烯,其中,介孔二氧化硅层的厚度为2~50nm,聚多巴胺层的厚度为1~30nm。The reduced graphene oxide is coated with polydopamine whose surface is modified with mesoporous silicon dioxide, wherein the thickness of the mesoporous silicon dioxide layer is 2-50 nm, and the thickness of the polydopamine layer is 1-30 nm. 2.根据权利要求1所述的基于石墨烯的药物载体,其特征在于,所述介孔二氧化硅层的厚度为5~20nm,多巴胺层的厚度为3~20nm,还原氧化石墨烯的尺寸为20~300nm。2. The drug carrier based on graphene according to claim 1, characterized in that, the thickness of the mesoporous silica layer is 5-20nm, the thickness of the dopamine layer is 3-20nm, and the size of the reduced graphene oxide 20-300nm. 3.一种基于石墨烯的药物载体的制备方法,其特征在于,包括步骤:3. A preparation method based on graphene-based drug carrier, characterized in that, comprising steps: S1将氧化石墨烯分散在pH值为8.0~9.0的缓冲溶液中,再加入多巴胺盐酸盐,50~90℃反应4~48小时,得聚多巴胺包覆还原氧化石墨烯;S1 Disperse graphene oxide in a buffer solution with a pH value of 8.0-9.0, then add dopamine hydrochloride, and react at 50-90°C for 4-48 hours to obtain polydopamine-coated reduced graphene oxide; S2将步骤S1所得聚多巴胺包覆还原氧化石墨烯分散在水溶液中,加入阳离子表面活性剂,调节pH值为10~12,加入有机硅烷,室温反应12~36小时,获得基于石墨烯的药物载体。S2 Disperse the polydopamine-coated reduced graphene oxide obtained in step S1 in an aqueous solution, add a cationic surfactant, adjust the pH value to 10-12, add organosilane, and react at room temperature for 12-36 hours to obtain a graphene-based drug carrier . 4.根据权利要求3所述的制备方法,其特征在于,步骤S1中,所述氧化石墨烯的尺寸为20~300nm,所述pH值为8.0~9.0的缓冲溶液为tris缓冲溶液。4. The preparation method according to claim 3, characterized in that, in step S1, the size of the graphene oxide is 20-300 nm, and the buffer solution with a pH value of 8.0-9.0 is a tris buffer solution. 5.根据权利要求3所述的制备方法,其特征在于,步骤S1中,氧化石墨烯与多巴胺盐酸盐的质量比为1~3:1;加入多巴胺盐酸盐后60~70℃反应12~24小时。5. The preparation method according to claim 3, characterized in that, in step S1, the mass ratio of graphene oxide to dopamine hydrochloride is 1-3:1; after adding dopamine hydrochloride, react at 60-70°C for 12 ~24 hours. 6.根据权利要求3所述的制备方法,其特征在于,步骤S2中,所述阳离子表面活性剂选自十六烷基三甲基溴化铵、十六烷基三甲基氯化铵、阳离子聚丙烯酰胺、苯扎氯铵、苯扎溴铵,阳离子表面活性剂在水溶液中的浓度为0.002~0.2mol/L。6. preparation method according to claim 3, is characterized in that, in step S2, described cationic surfactant is selected from hexadecyl trimethyl ammonium bromide, cetyl trimethyl ammonium chloride, The concentration of cationic polyacrylamide, benzalkonium chloride, benzalkonium bromide, and cationic surfactant in the aqueous solution is 0.002-0.2mol/L. 7.根据权利要求3所述的制备方法,其特征在于,步骤S2中,所述聚多巴胺包覆还原氧化石墨烯分散在水溶液中的浓度为0.005~1mg/mL,所述有机硅烷与聚多巴胺包覆还原氧化石墨烯的质量比为0.1~1。7. The preparation method according to claim 3, characterized in that, 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 organosilane and polydopamine The mass ratio of the coated reduced graphene oxide is 0.1-1. 8.根据权利要求3所述的制备方法,其特征在于,步骤S2中,所述有机硅烷为正硅酸乙酯、3-氨丙基三乙氧基硅烷、γ-巯丙基三甲氧基硅烷中的一种或多种。8. The preparation method according to claim 3, characterized in that, in step S2, the organosilane is ethyl orthosilicate, 3-aminopropyltriethoxysilane, γ-mercaptopropyltrimethoxy One or more of silanes. 9.根据权利要求3所述的制备方法,其特征在于,步骤S2反应后用甲醇和/或乙醇洗涤产物、离心分离。9. The preparation method according to claim 3, characterized in that, after the reaction in step S2, the product is washed with methanol and/or ethanol, and centrifuged. 10.权利要求1或2所述的基于石墨烯的药物载体在制备光热治疗试剂中的应用。10. The application of the graphene-based drug carrier according to claim 1 or 2 in the preparation of photothermal therapy reagents.
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