CN111803629A - Organic-inorganic hybrid multifunctional biological material based on nano cellulose crystals and preparation method and application thereof - Google Patents
Organic-inorganic hybrid multifunctional biological material based on nano cellulose crystals and preparation method and application thereof Download PDFInfo
- Publication number
- CN111803629A CN111803629A CN202010492059.2A CN202010492059A CN111803629A CN 111803629 A CN111803629 A CN 111803629A CN 202010492059 A CN202010492059 A CN 202010492059A CN 111803629 A CN111803629 A CN 111803629A
- Authority
- CN
- China
- Prior art keywords
- cnc
- pda
- nano
- organic
- inorganic hybrid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000013078 crystal Substances 0.000 title claims abstract description 68
- 229920001046 Nanocellulose Polymers 0.000 title claims abstract description 50
- 239000012620 biological material Substances 0.000 title claims abstract description 29
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 229920001690 polydopamine Polymers 0.000 claims abstract description 106
- 229920002678 cellulose Polymers 0.000 claims abstract description 40
- 239000001913 cellulose Substances 0.000 claims abstract description 40
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 40
- 239000002086 nanomaterial Substances 0.000 claims abstract description 33
- 239000000463 material Substances 0.000 claims abstract description 30
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 22
- 238000003384 imaging method Methods 0.000 claims abstract description 19
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 6
- 239000000758 substrate Substances 0.000 claims abstract description 4
- 230000008878 coupling Effects 0.000 claims abstract description 3
- 238000010168 coupling process Methods 0.000 claims abstract description 3
- 238000005859 coupling reaction Methods 0.000 claims abstract description 3
- 239000000243 solution Substances 0.000 claims description 45
- 239000006185 dispersion Substances 0.000 claims description 39
- 239000007788 liquid Substances 0.000 claims description 36
- 238000003756 stirring Methods 0.000 claims description 32
- 238000006243 chemical reaction Methods 0.000 claims description 27
- 239000002244 precipitate Substances 0.000 claims description 18
- 229910021642 ultra pure water Inorganic materials 0.000 claims description 18
- 239000012498 ultrapure water Substances 0.000 claims description 18
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 16
- 239000010931 gold Substances 0.000 claims description 16
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 12
- 239000007853 buffer solution Substances 0.000 claims description 11
- 239000003814 drug Substances 0.000 claims description 9
- 239000012467 final product Substances 0.000 claims description 9
- 229910052737 gold Inorganic materials 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 8
- 229960005070 ascorbic acid Drugs 0.000 claims description 8
- 235000010323 ascorbic acid Nutrition 0.000 claims description 8
- 239000011668 ascorbic acid Substances 0.000 claims description 8
- 239000002105 nanoparticle Substances 0.000 claims description 8
- 238000007626 photothermal therapy Methods 0.000 claims description 8
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 8
- 239000011259 mixed solution Substances 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 4
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 2
- 238000001132 ultrasonic dispersion Methods 0.000 claims 1
- 230000015784 hyperosmotic salinity response Effects 0.000 abstract description 11
- 230000000694 effects Effects 0.000 abstract description 10
- 238000010521 absorption reaction Methods 0.000 abstract description 6
- 150000003839 salts Chemical class 0.000 abstract description 5
- 241001301450 Crocidium multicaule Species 0.000 abstract 1
- 210000004027 cell Anatomy 0.000 description 16
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 14
- 239000002245 particle Substances 0.000 description 11
- 229960003638 dopamine Drugs 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 5
- 238000005286 illumination Methods 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- 230000008569 process Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- YMHOBZXQZVXHBM-UHFFFAOYSA-N 2,5-dimethoxy-4-bromophenethylamine Chemical compound COC1=CC(CCN)=C(OC)C=C1Br YMHOBZXQZVXHBM-UHFFFAOYSA-N 0.000 description 3
- 241000545067 Venus Species 0.000 description 3
- 238000005054 agglomeration Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 231100000135 cytotoxicity Toxicity 0.000 description 3
- 230000003013 cytotoxicity Effects 0.000 description 3
- 238000007865 diluting Methods 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 238000009210 therapy by ultrasound Methods 0.000 description 3
- 210000004881 tumor cell Anatomy 0.000 description 3
- 238000004506 ultrasonic cleaning Methods 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000703 high-speed centrifugation Methods 0.000 description 2
- 239000007777 multifunctional material Substances 0.000 description 2
- 231100000956 nontoxicity Toxicity 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000003223 protective agent Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 125000002353 D-glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 241000219146 Gossypium Species 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- 239000002262 Schiff base Substances 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- 238000003917 TEM image Methods 0.000 description 1
- 241000251555 Tunicata Species 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000956 alloy Substances 0.000 description 1
- 229910045601 alloy Inorganic materials 0.000 description 1
- 238000012984 biological imaging Methods 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical group OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 230000031700 light absorption Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000002159 nanocrystal Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000012634 optical imaging Methods 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000007669 thermal treatment Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 238000012285 ultrasound imaging Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Images
Classifications
-
- 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
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/59—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/60—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
-
- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/61—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/221—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by the targeting agent or modifying agent linked to the acoustically-active agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Acoustics & Sound (AREA)
- Physics & Mathematics (AREA)
- Radiology & Medical Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Abstract
The invention discloses an organic-inorganic hybrid multifunctional biomaterial based on nanocellulose crystal and a preparation method and application thereof, the material mainly Comprises Nanocellulose Crystal (CNC), Polydopamine (PDA) and gold nano star (AuNSs), the nanocellulose crystal is used as a substrate material, the polydopamine is used as a coupling material and can be used as a bridge beam connected between the nanocellulose crystal and the nano gold star, and the surface of the organic-inorganic hybrid nanomaterial is modified with polyethylene glycol molecules with certain functional end groups so as to ensure the salt tolerance and expandability of the nanomaterial in the internal environment of a living body. The material disclosed by the invention is simple to prepare and convenient to use, can greatly improve the salt resistance of the nano-crystalline cellulose, has strong absorption in a near-infrared region, has good biocompatibility and obvious photoacoustic signals and photothermal effect, and can realize the purposes of tumor imaging and tumor treatment.
Description
Technical Field
The invention relates to an organic-inorganic hybrid nano material used in the technical field of optoacoustic and photothermal, in particular to an organic-inorganic hybrid multifunctional biological material based on nanocellulose crystals and a preparation method and application thereof.
Background
The nano cellulose crystal (CNC) is a nano material formed by linear high polymer formed by D-glucose units connected by 1, 4-beta glycosidic bonds, and is extracted from green terrestrial and submarine plants and animal bodies, such as wood, cotton, bacteria, tunicates, and the like. Based on the rapid development of new biological economy, the high specific surface area, high crystallinity, high strength, biodegradability, nontoxicity, green environmental protection and other unique properties of CNC attract a lot of attention, and the demand thereof is increasing. Gold nanoparticles (AuNPs) are one of important members of a nano family, have the advantages of low toxicity, easiness in surface modification, strong biocompatibility, unique optical property and the like, and can finely regulate and control the particle size, the shape and the surface performance.
Photoacoustic imaging (PAI) is an emerging nonradiative, non-destructive imaging technique in the biomedical field that combines the high contrast, high resolution (220nm) of optical imaging with the high penetration (5cm) of ultrasound imaging. The principle is that biological tissues absorb light energy under the irradiation of pulse laser to convert the light energy into heat energy, so that the volume is periodically expanded, and the generated ultrasonic signals are collected to reconstruct an image of the biological tissues. Different tissues will then generate ultrasound of different intensities, which can be used to distinguish between normal and diseased tissue.
Photothermal therapy (PTT) is a widely used tumor treatment technique that uses light absorbers to generate heat to kill tumor cells. The gold nanoparticles have excellent photo-thermal conversion capacity due to the plasma resonance characteristics of the gold nanoparticles, the particles have strong absorption in a near-infrared region by adjusting the morphology of the nano-Au star particles, the requirements of organisms are met, the photo-thermal conversion efficiency is greatly improved, the nano-Au star has excellent photo-thermal effect, but the nano-Au star is easy to agglomerate due to the lack of a protective agent, and most of the protective agents have high biotoxicity.
Disclosure of Invention
The purpose of the invention is as follows: aiming at the problems that the salt tolerance of the nano-crystalline cellulose is low in physiological environment and the application of the nano-crystalline cellulose in biological imaging and treatment is greatly limited by the defect, the invention provides the organic-inorganic hybrid multifunctional biomaterial based on the nano-crystalline cellulose, which can greatly improve the salt tolerance of the nano-crystalline cellulose and has the functions of photo-thermal effect and photo-acoustic imaging.
The invention also provides a preparation method and application of the organic-inorganic hybrid multifunctional biomaterial based on the nano cellulose crystal.
The technical scheme is as follows: in order to achieve the above object, the organic-inorganic hybrid multifunctional biomaterial based on nanocellulose crystal according to the present invention is mainly Composed of Nanocellulose Crystal (CNC), Polydopamine (PDA) and gold nanostar (auss), wherein the nanocellulose crystal is used as a substrate material, the polydopamine is a coupling material and can be used as a bridge beam connected between the nanocellulose crystal and the nanostar, and the surface of the material is modified with polyethylene glycol molecules having certain functional end groups (amino and thiol) to ensure the salt tolerance and expandability of the nanomaterial in the in vivo environment.
The preparation method of the organic-inorganic hybrid multifunctional biomaterial based on the nano cellulose crystal comprises the following steps:
(1) the method is characterized in that compared with the existing preparation method, the method greatly shortens the reaction time and greatly improves the uniformity of a polydopamine layer wrapped on the surface;
specifically, the solution dispersed with 8-10 mg/mL of nano-cellulose crystals is subjected to ultrasonic treatment for 30-50 min by using a cell crushing instrument to obtain a uniformly dispersed nano-cellulose crystal solution; adding the nano-cellulose crystal dispersion liquid into a Tris-HCl buffer solution with the pH value of 8-10, wherein the concentration of CNC is 1-1.5 mg/mL, adding dopamine, wherein the concentration of dopamine is 1-1.5 mg/mL, placing a reaction system in an ultrasonic cleaning instrument for ultrasonic reaction for 2 hours, centrifuging at a high speed, taking a precipitate, purifying for 3 times, and preparing to obtain 1-1.5 mg/mL polydopamine modified nano-cellulose crystal particle CNC @ PDA NPs dispersion liquid;
(2) dispersing CNC @ PDA NPs into a buffer solution, and adding mPEG5000-NH2Stirring for reaction, centrifugally purifying after the reaction is finished, and removing excessive mPEG5000-NH2Preparing nano-cellulose/polydopamine (CNC @ PDA @ PEG NPs) dispersion liquid of the polydopamine surface modified mPEG5000-NH2 by using a catechol structure rich on the surface of the polydopamine to perform Schiff base reaction and Michael addition reaction with amino;
(3) placing the CNC @ PDA @ PEG NPs dispersion liquid prepared in the step (2) into a water bath for stirring, slowly adding a chloroauric acid solution, and growing gold nano seeds (AuSeeds) on the surface of the PDA in situ by utilizing the reducibility and the electrostatic adsorption capacity of the PDA, so as to prepare an organic-inorganic hybrid nanoparticle CNC @ PDA @ AuSeeds NPs dispersion liquid;
(4) stirring the dispersion liquid of the CNC @ PDA @ AuSeeds NPs at normal temperature, adding chloroauric acid, adding a mixed solution of HCl, silver nitrate and ascorbic acid, stopping stirring after the solution is changed from brown to blue gray, centrifuging, taking precipitate, and dispersing with ultrapure water to obtain the dispersion liquid of the organic-inorganic hybrid nano material CNC @ PDA @ AuNSs NPs of the polydopamine surface modified nano Venus point (AuNSs);
(5) adding mPEG5000-SH into the CNC @ PDA @ AuNSs NPs dispersion, and oscillating at room temperature; and centrifuging and purifying to obtain a final product CNC @ PDA @ AuNSs @ PEG NPs, namely the organic-inorganic hybrid multifunctional biomaterial based on the nano-cellulose crystal.
Dispersing CNC @ PDA NPs into Tris-HCl buffer solution with the pH value of 8-10 in the step (2), and finally enabling the concentration of the CNC @ PDA to be 1-1.5mg/mL, adding mPEG5000-NH2Final mPEG5000-NH2The concentration is 1-1.5 mg/mL, the mixture is stirred and reacted for 8-24 hours at the temperature of 40-60 ℃ at the speed of 300-400 r/min, after the reaction is finished, high-speed centrifugation (18000-20000 rpm) is carried out, precipitates are taken and re-dispersed with ultrapure water, and the excessive mPEG5000-NH is removed2And purifying for 3 times.
Preferably, CNC @ PDA NPs are dispersed in 10mL Tris-HCl buffer solution with pH 8.5, and mPEG5000-NH is added2Final mPEG5000-NH2The concentration is 1.5mg/mL, the reaction is carried out for 12h under the stirring at 50 ℃, the high-speed centrifugation and purification are carried out for 3 times, and the excessive mPEG5000-NH is removed2Preparing to obtain polydopamine surface modified mPEG5000-NH2The nano-crystalline cellulose particles CNC @ PDA @ PEG NPs.
Wherein, 10-11 mL of the CNC @ PDA @ PEGNPs solution prepared in the step (2) with the concentration of 1-1.5 mg/mL is placed in a water bath kettle at the temperature of 40-60 ℃ and stirred at a high speed of 1000-1200 r/min, 10-20 mu L of 1% (w/w) chloroauric acid solution is slowly added, stirring is kept at 1000-1200 r/min in the adding process, and stirring is stopped after reaction is carried out for 1-1.5 h.
Preferably, the CNC @ PDA @ PEG NPs solution is placed in a 50 ℃ water bath and stirred at a high speed, and the chloroauric acid solution is slowly added.
Wherein 10-11 mL of CNC @ PDA @ AuSeeds NPs solution with the concentration of 0.5-0.6 mg/mL is stirred at high speed of 1000-1200 r/min at normal temperature in the step (4), 0.8-1 mL of 5mM chloroauric acid is added, 15-25 muL of 1MHCl, 0.5-0.7 mL of 2mM silver nitrate and 0.1-0.3 mL0.1M ascorbic acid mixed solution are added, and stirring is continuously carried out in the process until the solution is changed from brownish red to blue gray, and then the stirring is stopped.
Preferably, the CNC @ PDA @ Au NPs solution is stirred at a high speed at normal temperature, chloroauric acid is firstly added, then an HCl solution is added, finally silver nitrate and ascorbic acid solutions in a certain proportion are rapidly added, the solution is changed from brown to blue gray, and stirring is stopped.
In the step (5), mPEG5000-SH with the final concentration of 1.0-1.5 mg/mL is added into 10-11 mL of CNC @ PDA @ AuNSs NPs solution with the concentration of 1.0-1.5 mg/mL, and the mixture is shaken at the room temperature of 180-200 rpm for 8-10 h; and after the reaction is finished, centrifuging to remove the upper layer liquid, taking the precipitate, and redispersing the precipitate with ultrapure water to obtain the final product CNC @ PDA @ AuNSs @ PEG NPs.
Preferably, in step (5), a final concentration of 1.5mg/mLmPEG5000-SH is added to the CNC @ PDA @ AuNSs NPs dispersion and shaken at room temperature and 200rpm for 8 h.
The organic-inorganic hybrid multifunctional biomaterial based on the nano cellulose crystal has excellent light absorption capacity within the wavelength range of 700-1000nm, and has good response to photoacoustic laser.
The organic-inorganic hybrid multifunctional biomaterial based on the nano cellulose crystal has excellent salt tolerance, and can stably exist in 0.01M PBS buffer solution for cell culture for a long time (more than or equal to 7 days) without agglomeration.
The invention relates to application of an organic-inorganic hybrid multifunctional biomaterial based on nano cellulose crystals in preparation of a photoacoustic imaging drug.
Further, the organic-inorganic hybrid multifunctional biomaterial based on the nano cellulose crystal is applied to the preparation of tumor photoacoustic imaging drugs.
The invention relates to application of an organic-inorganic hybrid multifunctional biomaterial based on nano cellulose crystals in preparing a medicament for photothermal therapy.
Further, the application of the organic-inorganic hybrid multifunctional biomaterial based on the nano cellulose crystal in preparing a tumor photothermal therapy medicine.
The invention relates to application of an organic-inorganic hybrid multifunctional biomaterial based on nano cellulose crystals in preparation of a medicine or a reagent for photoacoustic imaging of living tumors.
The invention relates to an organic-inorganic hybrid multifunctional biomaterial (CNC @ PDA @ AuNSs @ PEG NPs) based on a nano cellulose crystal, which is applied to photoacoustic imaging and tumor photothermal therapy, in particular to photoacoustic imaging research and photothermal therapy of tumors, and specifically comprises the following steps: performing sample photoacoustic imaging on the CNC @ PDA @ AuNSs @ PEG NPs; the compound is applied to tumor cells, generates photothermal effect under the irradiation of near-infrared laser, kills the tumor cells and realizes tumor photothermal treatment.
According to the invention, nano-crystalline cellulose (CNC) is used as a template, a layer of polydopamine is wrapped on the surface of the CNC, nano-Au star is adsorbed on the polydopamine through static electricity, a large number of long-chain PEG modified on the polydopamine on the surface of the CNC improves the anti-agglomeration performance of the naked CNC, and the nano-Au star is fixed on the polydopamine on the surface of the CNC, so that the problem that the Au nano-Au star is easy to agglomerate is avoided, and in addition, the material is endowed with excellent photo-thermal performance.
The diameter of the selected nano-crystalline cellulose is 3-10 nm, the length of the selected nano-crystalline cellulose is 100-500 nm, and the suspension liquid of the nano-crystalline cellulose has excellent stability. By utilizing the hybridization of nano-gold particles (AuNSs) and nano-cellulose crystals, the obtained material has the characteristics of non-toxicity, degradability and the like of the nano-cellulose crystals and has stronger absorption in near infrared.
According to the invention, nano-crystalline cellulose (CNC) is used as a substrate material, dopamine monomer is introduced to be self-polymerized on the surface of the nano-crystalline cellulose to form a poly-dopamine shell layer, nano-Venus particles are modified on the poly-dopamine shell layer to enhance the absorption strength, and long-chain polyethylene glycol (PEG) is modified to increase the biocompatibility and salt tolerance, so that the organic-inorganic hybrid multifunctional biological material is obtained.
Has the advantages that: compared with the prior art, the invention has the following advantages:
1. the organic-inorganic hybrid multifunctional biomaterial (CNC @ PDA @ AuNSs @ PEG NPs) based on the nano-crystalline prepared by the invention integrates the excellent template property of the nano-crystalline, the high biocompatibility of polydopamine, and the excellent photo-thermal effect and photo-acoustic response of gold nanoparticles;
2. the organic-inorganic hybrid multifunctional biomaterial (CNC @ PDA @ AuNSs @ PEG NPs) based on the nano-cellulose crystal has the advantages of simple preparation process, mild experimental conditions, only water bath, simple purification method and only centrifugation, and has higher uniformity of a polydopamine layer on the surface of CNC @ PDA prepared by ultrasonic compared with the existing method for wrapping PDA on the surface of CNC;
3. the nano-cellulose-based crystal prepared by the inventionThe organic-inorganic hybrid multifunctional biomaterial (CNC @ PDA @ AuNSs @ PEG NPs) is sequentially modified by a large amount of mPEG5000-NH2The mPEG5000-SH greatly improves the problem of low salt tolerance of the nano-crystalline cellulose in physiological environment, and greatly expands the biological application after improving the salt tolerance of the nano-crystalline cellulose;
4. the organic-inorganic hybrid multifunctional biomaterial (CNC @ PDA @ AuNSs @ PEG NPs) based on the nano-crystalline cellulose prepared by the invention has excellent biocompatibility and almost negligible cytotoxicity;
5. the CNC @ PDA @ AuNSs @ PEG NPs prepared by the invention has strong and wide near-infrared absorption, so that the CNC @ PDA @ AuNSs @ PEG NPs have photoacoustic response in a near-infrared region, and simultaneously have excellent photothermal effect by matching with the plasma resonance effect of alloy nanoparticles, thereby being an excellent multifunctional nano material integrating imaging and treatment based on nano cellulose crystals.
Drawings
FIG. 1 is a process for preparing organic-inorganic multifunctional hybrid nanomaterial based on nanocellulose crystal in example 1 of the present invention;
FIG. 2 is a representation of UV-Vis of the organic-inorganic multifunctional hybrid nanomaterial based on nanocellulose crystal in example 1 of the present invention;
FIG. 3 is a TEM image of the organic-inorganic hybrid multifunctional nanomaterial based on nanocellulose crystal in example 1 of the present invention;
FIG. 4 is a graph of photoacoustic signal versus concentration of organic-inorganic hybrid multifunctional nanomaterial based on nanocellulose crystal and a photoacoustic imaging graph of a sample in example 2 of the present invention;
FIG. 5 is a graph of in vitro photo-thermal temperature rise of organic-inorganic hybrid multifunctional nano-materials based on nano-crystalline cellulose in example 3 of the present invention;
FIG. 6 is a cytotoxicity diagram of organic-inorganic hybrid multifunctional nanomaterial based on nanocellulose crystal in example 4 of the present invention;
FIG. 7 is a graph showing the photothermal treatment effect of cancer cells of the organic-inorganic hybrid multifunctional nanomaterial based on nanocellulose crystal in example 5 of the present invention (indicators are AM and PI, excitation wavelengths are 488nm and 515nm, respectively, and emission wavelengths are 500-550 nm and 600-650 nm, respectively);
FIG. 8 is a graph showing the improvement of salt tolerance of the organic-inorganic hybrid multifunctional nanomaterial based on nanocellulose crystal in example 6 of the present invention;
fig. 9 is a photoacoustic image of the tumor of the organic-inorganic hybrid multifunctional nanomaterial based on nanocellulose crystal in example 6 of the present invention.
Detailed Description
The invention will be better understood from the following examples. It is easily understood by those skilled in the art that the descriptions of the embodiments are only for illustrating the present invention and should not be construed as limiting the present invention as detailed in the claims. Materials, reagents and the like used in the following examples are commercially available unless otherwise specified. The experimental procedures, in which specific conditions are not indicated in the examples, are generally carried out under conventional conditions or conditions recommended by the manufacturer.
Example 1:
the preparation process is shown in figure 1, and the preparation method of the organic-inorganic hybrid multifunctional nano material based on the cellulose nanocrystals comprises the following steps: (wherein the concentration of the solution or dispersion prepared in each step is calculated on the basis of CNC)
(1) Carrying out ultrasonic treatment on high-concentration (10mg/mL) Cellulose Nanocrystalline (CNC) aqueous solution dispersion liquid at 100kHz for 30min by using a cell crushing instrument to obtain uniformly dispersed CNC dispersion liquid;
(2) diluting 10mg/mL CNC dispersion liquid to 1mg/mL with Tris-HCl (10mM, pH 8.5) buffer solution, adding dopamine to ensure that the concentration of the dopamine in the system is 1mg/mL, placing the reaction system in an ultrasonic cleaning instrument for 50kHz ultrasonic reaction for 3h, centrifuging at a high speed (20000rpm, 20min), taking the upper layer for purification for 3 times, and preparing to obtain the polydopamine modified nano-cellulose crystal particle @ CNC PDA NPs dispersion liquid;
(3) centrifuging and re-dispersing the CNC @ PDA NPs dispersion liquid in the step (2) into 10mM Tris-HCl buffer solution with the pH value of 8.5, wherein the final concentration of the CNC @ PDA is 1mg/mL, and adding mPEG5000-NH2Ensuring mPEG5000-NH2The final concentration of the reaction solution is 1.5mg/mL, the reaction solution is stirred at a low speed of 400r/min at 50 ℃ for 12 hours, the reaction solution is centrifuged at a high speed (20000rpm, 30 minutes) to take precipitates, the precipitates are dispersed by ultrapure water, the purification is carried out for 3 times, and the excessive mPEG5000-NH is removed2Preparing to obtain polydopamine surface modified mPEG5000-NH2The dispersion liquid of nano-cellulose crystal particles (CNC @ PDA @ SH-PEG);
(4) placing 10mL of dispersion liquid with the concentration of 1/mL in the step (3) into a 50 ℃ water bath kettle, stirring at a high speed of 1000r/min, slowly adding 10 mu L of 1% (w/w) chloroauric acid solution, keeping stirring at 1000r/min in the adding process, stopping stirring after reacting for 1h, and standing for 30min to prepare the organic-inorganic hybrid nano-particle CNC @ PDA @ AuSeeds NPs dispersion liquid of the poly-dopamine surface-modified nano-gold spheres;
(5) stirring 10mL of CNC @ PDA @ AuSeeds NPs solution with the concentration of 0.5mg/mL at a high speed at the normal temperature of 1000r/min, adding 1mL of 5mM chloroauric acid, adding 20 mu L of 1M hydrochloric acid solution to adjust the pH value of the system to subacidity, simultaneously quickly adding 0.6mL of mixed solution of 2mM silver nitrate and 0.2mL of 0.1M ascorbic acid, keeping the violent stirring at 1000r/min in the reaction process, stopping stirring after the solution changes from brownish red to blue gray, centrifugally removing the upper layer liquid, dispersing the precipitate by using ultra-pure water, and preparing the organic-inorganic hybrid nano material CNC @ PDA @ AuNSs NPs dispersion liquid of polydopamine surface modified nano Venus (AuNSs);
(6) adding mPEG5000-SH into 10mL of CNC @ PDA @ AuNSs NPs solution with the concentration of 1.0mg/mL, ensuring that the final concentration of the mPEG5000-SH is 1.5mg/mL, oscillating and reacting at room temperature of 200rpm for 8 hours, and further improving the salt resistance of the material; and (3) washing the obtained product with ultrapure water, centrifuging (4000rpm for 20min), taking precipitate, dispersing the precipitate with 10mL of ultrapure water, purifying for 3 times to obtain a dispersion liquid of a final product, namely the organic-inorganic hybrid multifunctional material CNC @ PDA @ AuNSs @ PEG NPs, with the concentration of 1.0mg/mL, preserving for later use, and diluting or concentrating the final product with the ultrapure water in a subsequent experiment.
The UV-Vis characterization is carried out on the final product CNC @ PDA @ AuNSs @ PEG NPs, the result is shown in figure 2, and the CNC @ PDA @ AuNSs @ PEG has a wide absorption band in the range of 500-900 nm. The final product CNC @ PDA @ AuNSs @ PEG NPs was topographically characterized using a Transmission Electron Microscope (TEM), and it can be seen from fig. 3 that a large number of nanogold particles (dark color) are distributed on the rod-like nanocellulose crystal (light color).
Example 2
In-vitro photoacoustic signal test of the organic-inorganic hybrid nanomaterial based on the nanocellulose crystal:
the organic-inorganic hybrid multifunctional nanomaterial based on nanocellulose crystal prepared in example 1 was configured with ultrapure water as solvent in the following concentration gradient: 0.1mg/mL, 0.32mg/mL, 3.16mg/mL, 6mg/mL, 8mg/mL, 10mg/mL, the above-mentioned concentration material was placed in a centrifuge tube using a wavelength of 720nm and a power density of 0.5W/cm2The laser collects photoacoustic signals, and different wavelengths are selected to collect photoacoustic signals by 0.4 mg/mL. The results are shown in fig. 4, wherein (a) shows that the concentration of the material is in linear relation with the photoacoustic intensity, and (b) and (c) are respectively 2D and 3D photoacoustic imaging graphs of the material in the cuvette, wherein white bright spots are photoacoustic responses generated after the material is irradiated by laser, and fig. 4 shows that the organic-inorganic hybrid nano-material based on the nano-cellulose crystal has excellent photoacoustic signals.
Example 3
The in vitro photo-thermal performance test of the organic-inorganic hybrid nano material based on the nano cellulose crystal comprises the following steps:
the organic-inorganic hybrid multifunctional nanomaterial solution based on nanocellulose crystal prepared in example 1 was prepared with ultrapure water with the following concentration gradient: 0.05mg/mL, 0.1mg/mL, 0.15mg/mL, 0.2mg/mL, and using ultrapure water as a control, the above concentrations of materials were placed in a centrifuge tube using a wavelength of 635nm and a power density of 0.5W/cm2Irradiating for 6 min. As shown in FIG. 5, it can be seen that the temperature rise of pure water under laser irradiation is very small, while the temperature rises to different degrees in materials with different concentrations after laser irradiation, and the temperature rise of 0.2mg/mL material can reach 30 ℃, and FIG. 5 shows that the organic-inorganic hybrid nanomaterial based on nanocellulose crystals has excellent photothermal properties.
Example 4
And (3) testing cytotoxicity of the organic-inorganic hybrid nano material based on the nano cellulose crystal:
the organic-inorganic hybrid multifunctional nanomaterial solution based on nanocellulose crystals prepared in example 1 was configured using an incomplete culture solution with the following concentration gradient: 0.03mg/mL, 0.06mg/mL, 0.12mg/mL, 0.25mg/mL, 0.5 mg/mL. The Hela cells are placed in a 96-well plate, after the cells are cultured for 24 hours and adhere to the wall, culture solution in the wells is changed into materials with the same quantity and the concentration, one material is kept as a control group, and after the cells and the materials are incubated for 24 hours, MTT reagent is added for incubation for 4 hours. The results are shown in fig. 6, the cell activity is higher than 75%, and fig. 6 shows that the organic-inorganic hybrid nano-material based on nano-cellulose crystal is almost non-toxic.
Example 5
Testing the photo-thermal treatment effect of the cancer cells of the organic-inorganic hybrid nano material based on the nano cellulose crystal:
hela cells were cultured in a confocal dish for 24 hours to allow the cells to be completely attached to the wall, the culture solution in the dish was changed to a culture solution mixed with the material prepared in example 1 (the concentration of the material in the culture solution is 0.25mg/mL) and incubated for 24 hours, the culture solution in the dish was changed to an incomplete culture solution, and the wavelength was 635nm, and the power density was 0.5W/cm2Irradiating for 2min, incubating for 4h after the irradiation is finished, and then performing fluorescence imaging after the AM/PI staining method. As shown in fig. 7, AM can stain living cells, while PI can stain dead cells, (a) and (b) are AM/PI staining without illumination group, illumination money shows strong AM fluorescence, which indicates that most of cancer cells survive before illumination, (c) and (d) are AM/PI staining after laser illumination, and fluorescence showing strong PI after illumination indicates that most of cancer cells die, which indicates that the organic-inorganic hybrid nanomaterial based on nanocellulose crystals has a good photothermal killing effect on cancer cells.
Example 6
The salt resistance test of the organic-inorganic hybrid nano material based on the nano cellulose crystal comprises the following steps:
the salt resistance of CNC, CNC @ PDA @ PEG and CNC @ PDA @ AuNSs @ PEG were compared, 500. mu.L of 0.01M PBS was added to each of the three materials at 500. mu.L of 1mg/mL, and the three materials were followed up and observed. As shown in FIG. 8, it can be seen that the CNC dispersion was clear and transparent (CNC in FIG. 8) and became cloudy and opaque immediately after PBS was added (CNC + PBS in FIG. 8), while the CNC @ PDA @ PEG made by CNC had significantly improved salt tolerance, specifically 500 μ L1mg/mL CNC @ PDA @ PEG with 500 μ L0.01M PBS added until 120h before significant agglomeration began (CNC @ PDA @ PEG + PBS 120h in FIG. 8), and the CNC @ PDA @ AuNSs @ PEG finally made had significantly improved salt tolerance, specifically 500 μ L1mg/mL CNC @ AuNSs @ PEG with 500 μ L0.01M PBS added to it which remained clear and transparent (third line in FIG. 8).
Example 7
Tumor imaging of organic-inorganic hybrid nanomaterials based on nanocellulose crystals:
1mL of 1mg/mL CNC @ PDA @ AuNSs @ PEG dispersion liquid is subcutaneously injected into a tumor part of a mouse by 250 mu L every 1h for four times, the mouse is placed in a small animal photoacoustic imaging instrument after the injection is finished for 2h and photoacoustic imaging is carried out by adopting 720nm laser to obtain a graph 9, the graph is distinguished from a black area, white bright spots are tumor tissues, the blood vessel distribution of the tumor tissue part can be clearly seen, and the CNC @ PDA @ AuNSs @ PEG can be applied to the photoacoustic imaging of living tumors.
Example 8
(1) Carrying out ultrasonic treatment on high-concentration (10mg/mL) Cellulose Nanocrystalline (CNC) aqueous solution dispersion liquid at 100kHz for 30min by using a cell crushing instrument to obtain uniformly dispersed CNC dispersion liquid;
(2) diluting 10mg/mL CNC dispersion liquid to 1.5mg/mL with Tris-HCl (10mM, pH 8) buffer solution, adding dopamine to ensure that the concentration of the dopamine in the system is 1.5mg/mL, placing the reaction system in an ultrasonic cleaning instrument for 50kHz ultrasonic reaction for 3h, centrifuging at high speed (18000rpm for 20min), taking the upper layer for purification for 3 times, and preparing to obtain the poly-dopamine modified nano-cellulose crystal particle CNC @ PDA NPs dispersion liquid;
(3) centrifuging and re-dispersing the CNC @ PDA NPs dispersion liquid in the step (2) into 10mM Tris-HCl buffer solution with the pH value of 8.5, wherein the final concentration of the CNC @ PDA is 1.5mg/mL, and adding mPEG5000-NH2Ensuring mPEG5000-NH2The final concentration of (2) is 1mg/mL, the reaction is carried out at 60 ℃ under the low-speed stirring of 400r/min for 8h, and the precipitate is centrifuged at high speed (18000rpm, 20min) to obtainDispersing with ultrapure water, purifying for 3 times, and removing excessive mPEG5000-NH2Preparing to obtain polydopamine surface modified mPEG5000-NH2The dispersion of nanocellulose crystal particles of (a);
(4) placing 10mL of dispersion liquid with the concentration of 1.5mg/mL in the step (3) into a 50 ℃ water bath kettle and stirring at a high speed of 1200r/min, slowly adding 20 mu L of 1% (w/w) chloroauric acid solution, keeping stirring at 1200r/min in the adding process, stopping stirring after reacting for 1.5h, and standing for 30-40 min to prepare the organic-inorganic hybrid nano-particle @ CNC PDA @ AuSeeds NPs dispersion liquid of the polydopamine surface modification nano-gold ball;
(5) stirring 10mL of CNC @ PDA @ AuSeeds NPs solution with the concentration of 0.75mg/mL at high speed at the normal temperature of 1200r/min, adding 0.8mL of 5mM chloroauric acid, adding 15 μ L of 1M hydrochloric acid solution to adjust the pH value of the system to be weakly acidic, simultaneously quickly adding 0.5mL of mixed solution of 2mM silver nitrate and 0.1mL of 0.1M ascorbic acid, keeping 1200r/min of vigorous stirring in the reaction process, stopping stirring after the color of the solution is changed from brownish red to blue gray, centrifugally removing the upper layer liquid, dispersing the precipitate by using ultrapure water, and preparing the organic-inorganic hybrid nano material CNC @ PDA @ AuNSNPs dispersion liquid of the polydopamine surface modified nano Venus (AuNSs);
(6) adding mPEG5000-SH into 10mL of CNC @ PDA @ AuNSs NPs solution with the concentration of 1.5mg/mL, ensuring that the final concentration of the mPEG5000-SH is 1.5mg/mL, and carrying out oscillation reaction at room temperature of 180rpm for 10 hours, thereby further improving the salt resistance of the material; and (3) washing the obtained product with ultrapure water, centrifuging (4000-5000), taking precipitate, dispersing the precipitate with 10mL of ultrapure water again, and purifying for 3 times to obtain a final product, namely the organic-inorganic hybrid multifunctional material CNC @ PDA @ AuNSs @ PEG NPs with the concentration of 1.5 mg/mL.
Example 9
Example 9 the same procedure as in example 1 was conducted except that in step (3), 5mM chloroauric acid (1 mL) was added, 5mM HCl (25. mu.L), 2mM silver nitrate (0.7 mL), and ascorbic acid (0.3 mL, 0.1M) were added, and stirring was continued until the solution changed from reddish brown to grayish blue in step (5) with stirring at a low speed of 300r/min for 24 hours.
The above description is only of the preferred embodiments of the present invention, and it should be noted that: it will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the principles of the invention and these are intended to be within the scope of the invention.
Claims (10)
1. The organic-inorganic hybrid multifunctional biomaterial based on the nano-cellulose crystal is characterized by mainly comprising the nano-cellulose crystal (CNC), Polydopamine (PDA) and gold nano-stars (AuNSs), wherein the nano-cellulose crystal is used as a substrate material, the polydopamine is used as a coupling material and used as a bridge connected between the nano-cellulose crystal and the nano-stars, and the surface of the material is modified with polyethylene glycol molecules with functional end groups.
2. The preparation method of the organic-inorganic hybrid multifunctional biomaterial based on the nanocellulose crystal as claimed in claim 1, characterized by comprising the following steps:
(1) preparing nano-cellulose/polydopamine (CNC @ PDANPs) dispersion liquid by adopting an ultrasonic dispersion method;
(2) dispersing CNC @ PDA NPs into a buffer solution, and adding mPEG5000-NH2Stirring for reaction, centrifugally purifying after the reaction is finished, and removing excessive mPEG5000-NH2To prepare polydopamine surface modified mPEG5000-NH2The nanocellulose/polydopamine (CNC @ PDA @ PEG NPs) dispersion of (a);
(3) placing the CNC @ PDA @ PEG NPs solution prepared in the step (2) into a water bath for stirring, and slowly adding a chloroauric acid solution to prepare an organic-inorganic hybrid nanoparticle (CNC @ PDA @ AuSeeds NPs) dispersion liquid;
(4) stirring the dispersion liquid of CNC @ PDA @ AuSeeds NPs at normal temperature, adding chloroauric acid, adding a mixed solution of HCl, silver nitrate and ascorbic acid, stopping stirring after the solution is changed from brown to blue gray, centrifugally removing upper-layer liquid, dispersing precipitates by using ultrapure water to prepare an organic-inorganic hybrid nano material (CNC @ PDA @ AuNSsNPs) dispersion liquid of polydopamine surface modified nano-gold stars (AuNSs);
(5) adding mPEG5000-SH into the CNC @ PDA @ AuNSs NPs dispersion, and oscillating at room temperature; and centrifuging and purifying to obtain a final product CNC @ PDA @ AuNSs @ PEG NPs, namely the organic-inorganic hybrid multifunctional biomaterial based on the nano-cellulose crystal.
3. The preparation method of claim 2, wherein the step (2) comprises dispersing CNC @ PDA NPs into Tris-HCl buffer solution with pH of 8-10 to obtain a final concentration of 1-1.5 mg/mL, and adding mPEG5000-NH2Final mPEG5000-NH2The concentration is 1-1.5 mg/mL, the mixture is stirred and reacted for 8-24 hours at the temperature of 40-60 ℃, after the reaction is finished, the mixture is centrifuged at high speed, precipitates are taken out and redispersed by ultrapure water, and excessive mPEG5000-NH is removed2。
4. The preparation method of claim 2, wherein the CNC @ PDA @ PEG NPs dispersion prepared in step (2) and having a concentration of 1-1.5 mg/mL is placed in a water bath kettle at 40-60 ℃ and stirred at a high speed in step (3), 1% (w/w) chloroauric acid solution is slowly added, stirring is kept during the addition, and stirring is stopped after the reaction is carried out for 1-1.5 h.
5. The method according to claim 2, wherein in the step (4), the CNC @ PDA @ AuSeeds NPs solution is stirred at a high speed at normal temperature, chloroauric acid is added, HCl is added, a mixed solution of silver nitrate and ascorbic acid is rapidly added, and stirring is continued until the solution changes from red brown to blue gray, and then is stopped.
6. The preparation method of claim 2, wherein mPEG5000-SH is added to the dispersion of 1.0-1.5 mg/mLCNC @ PDA @ AuNSs NPs in the step (5), and the final concentration of mPEG5000-SH is 1.0-1.5 mg/mL and the mixture is shaken at room temperature for 8-10 h; and after the reaction is finished, centrifuging to remove the upper layer liquid, taking the precipitate, and redispersing the precipitate with ultrapure water to obtain the final product CNC @ PDA @ AuNSs @ PEG NPs.
7. Use of the nanocellulose crystal-based organic-inorganic hybrid multifunctional biomaterial of claim 1 in the preparation of a photoacoustic imaging drug.
8. The use according to claim 7, characterized in that the organic-inorganic hybrid multifunctional biomaterial based on nanocellulose crystals is used for preparing drugs for photoacoustic imaging of tumors.
9. Use of the nanocellulose crystal-based organic-inorganic hybrid multifunctional biomaterial of claim 1 for the preparation of a medicament for photothermal therapy.
10. The use according to claim 7, characterized in that the organic-inorganic hybrid multifunctional biomaterial based on nanocellulose crystals is used for preparing a medicament for tumor photothermal therapy.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010492059.2A CN111803629A (en) | 2020-06-02 | 2020-06-02 | Organic-inorganic hybrid multifunctional biological material based on nano cellulose crystals and preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010492059.2A CN111803629A (en) | 2020-06-02 | 2020-06-02 | Organic-inorganic hybrid multifunctional biological material based on nano cellulose crystals and preparation method and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111803629A true CN111803629A (en) | 2020-10-23 |
Family
ID=72847901
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010492059.2A Pending CN111803629A (en) | 2020-06-02 | 2020-06-02 | Organic-inorganic hybrid multifunctional biological material based on nano cellulose crystals and preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111803629A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113368077A (en) * | 2021-04-27 | 2021-09-10 | 山东师范大学 | Polydopamine-modified nano covalent organic framework and preparation method and application thereof |
| CN113521304A (en) * | 2021-07-09 | 2021-10-22 | 华南理工大学 | Double-curative-effect anti-tumor drug based on nano-cellulose load and preparation method thereof |
| CN114958713A (en) * | 2022-05-31 | 2022-08-30 | 杭州赫贝科技有限公司 | Three-dimensional cell culture support of tubular structure |
| IT202200011450A1 (en) | 2022-05-31 | 2023-12-01 | St Europeo Di Oncologia S R L | Hybrid multifunctional cellulose-gold nanocrystal nanoplatform and its use in medicine |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104083760A (en) * | 2014-07-01 | 2014-10-08 | 中国人民解放军南京军区南京总医院 | PH-sensitive nanometer gold star material as well as preparation method and application thereof |
| US20170142975A1 (en) * | 2014-07-22 | 2017-05-25 | Celluforce Inc. | Polydopamine functionalized cellulose nanocrystals (pd-cncs) and uses thereof |
| CN108424522A (en) * | 2018-04-13 | 2018-08-21 | 河南省科学院能源研究所有限公司 | A kind of nano-cellulose/poly-dopamine/polyethylene glycol composite material and preparation method |
| CN110384806A (en) * | 2019-08-26 | 2019-10-29 | 西南大学 | Carry medicine poly-dopamine/dendrimer-gold nano grain preparation and application |
-
2020
- 2020-06-02 CN CN202010492059.2A patent/CN111803629A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104083760A (en) * | 2014-07-01 | 2014-10-08 | 中国人民解放军南京军区南京总医院 | PH-sensitive nanometer gold star material as well as preparation method and application thereof |
| US20170142975A1 (en) * | 2014-07-22 | 2017-05-25 | Celluforce Inc. | Polydopamine functionalized cellulose nanocrystals (pd-cncs) and uses thereof |
| CN108424522A (en) * | 2018-04-13 | 2018-08-21 | 河南省科学院能源研究所有限公司 | A kind of nano-cellulose/poly-dopamine/polyethylene glycol composite material and preparation method |
| CN110384806A (en) * | 2019-08-26 | 2019-10-29 | 西南大学 | Carry medicine poly-dopamine/dendrimer-gold nano grain preparation and application |
Non-Patent Citations (2)
| Title |
|---|
| FENGYANG WANG等: "Polydopamine-Functionalized Graphene Oxide Loaded with Gold Nanostars and Doxorubicin for Combined Photothermal and Chemotherapy of Metastatic Breast Cancer", 《ADV. HEALTHCARE MATER》 * |
| JIBIN SONG等: "New Generation of Gold Nanoshell-Coated Esophageal Stent: Preparation and Biomedical Applications", 《ACS APPL. MATER. INTERFACES》 * |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113368077A (en) * | 2021-04-27 | 2021-09-10 | 山东师范大学 | Polydopamine-modified nano covalent organic framework and preparation method and application thereof |
| CN113368077B (en) * | 2021-04-27 | 2022-06-21 | 山东师范大学 | Polydopamine-modified nano covalent organic framework and preparation method and application thereof |
| CN113521304A (en) * | 2021-07-09 | 2021-10-22 | 华南理工大学 | Double-curative-effect anti-tumor drug based on nano-cellulose load and preparation method thereof |
| CN113521304B (en) * | 2021-07-09 | 2023-12-12 | 华南理工大学 | Dual-curative-effect anti-tumor drug based on nanocellulose load and preparation method thereof |
| CN114958713A (en) * | 2022-05-31 | 2022-08-30 | 杭州赫贝科技有限公司 | Three-dimensional cell culture support of tubular structure |
| IT202200011450A1 (en) | 2022-05-31 | 2023-12-01 | St Europeo Di Oncologia S R L | Hybrid multifunctional cellulose-gold nanocrystal nanoplatform and its use in medicine |
| WO2023233281A1 (en) | 2022-05-31 | 2023-12-07 | Università Degli Studi Di Firenze | Multifunctional hybrid cellulose nanocrystals-gold nanoplatform and use thereof in medicine |
| CN114958713B (en) * | 2022-05-31 | 2024-02-20 | 杭州赫贝科技有限公司 | Three-dimensional cell culture support of tubular structure |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN111803629A (en) | Organic-inorganic hybrid multifunctional biological material based on nano cellulose crystals and preparation method and application thereof | |
| Yang et al. | A single 808 nm near-infrared light-mediated multiple imaging and photodynamic therapy based on titania coupled upconversion nanoparticles | |
| CN108578716B (en) | Polydopamine-coated magnetic mesoporous silica nano material and preparation and application thereof | |
| CN109364245A (en) | A kind of poly-dopamine nanometer diagnosis and treatment agent and preparation method thereof | |
| CN112641946A (en) | Polydopamine-coated gold nano-composite, preparation method thereof and application thereof in multi-modal tumor diagnosis and treatment | |
| CN112007170B (en) | Immune adjuvant functionalized metal organic framework material and preparation method and application thereof | |
| CN111358964A (en) | Magnetic octahedral platinum-doped gold nanoshell, and preparation method and application thereof | |
| CN116654986B (en) | Manganese sulfide nanoflower integrated diagnosis and treatment preparation and preparation method and application thereof | |
| CN105288625B (en) | A kind of porous Bi2Se3Nanosponges material, its preparation method and application | |
| CN108578427B (en) | Folic acid modified gold nanoparticle, preparation method thereof and application of gold nanoparticle in preparation of radiosensitization treatment drug | |
| Luo et al. | Rose bengal-modified gold nanorods for PTT/PDT antibacterial synergistic therapy | |
| CN116477668B (en) | Two-dimensional ferric sulfide nano-sheet and preparation method and application thereof | |
| CN110743013B (en) | Up-conversion nano composite material for dual-power cooperative treatment, preparation method and application | |
| Jin et al. | A biodegradable multifunctional nanoplatform based on antimonene nanosheets for synergistic cancer phototherapy and dual imaging | |
| CN110755640B (en) | Preparation method and application of gold-platinum composite nano diagnosis and treatment agent | |
| CN110559453B (en) | Magnetic nano-particles for imaging guidance and preparation method thereof | |
| Yang et al. | Smart supramolecular nanosystems for bioimaging and drug delivery | |
| CN106860865B (en) | A kind of Ni0.85Se nano material and its preparation method and application | |
| CN107303388B (en) | Diagnostic and therapeutic preparation based on near-infrared dye-hyaluronic acid complex | |
| CN113633789B (en) | Liquid metal nano probe integrating light acoustic imaging and drug inclusion and preparation method thereof | |
| CN106492236B (en) | A kind of multifunctional nano probe and its preparation method and application | |
| Wei et al. | Carbon dots based on targeting unit inheritance strategy for Golgi apparatus-targeting imaging | |
| CN111110864A (en) | Organic conjugated small molecule nano particle and preparation method and application thereof | |
| JP3826402B2 (en) | Dispersion containing photocatalytic titanium dioxide composite fine particles | |
| JP2008094816A (en) | Ultrasonic cancer therapy promoter |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20201023 |
|
| RJ01 | Rejection of invention patent application after publication |