CN113797226A - Ammonia borane/silicon ball/mesoporous silicon dioxide nano composite particle and preparation and application thereof - Google Patents

Ammonia borane/silicon ball/mesoporous silicon dioxide nano composite particle and preparation and application thereof Download PDF

Info

Publication number
CN113797226A
CN113797226A CN202111073604.5A CN202111073604A CN113797226A CN 113797226 A CN113797226 A CN 113797226A CN 202111073604 A CN202111073604 A CN 202111073604A CN 113797226 A CN113797226 A CN 113797226A
Authority
CN
China
Prior art keywords
sio
msio
nano
water
ammonia borane
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.)
Granted
Application number
CN202111073604.5A
Other languages
Chinese (zh)
Other versions
CN113797226B (en
Inventor
王烨颖
王依婷
刘毅
王伟恒
王镜
闫志强
俞磊
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
East China Normal University
Original Assignee
East China Normal University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by East China Normal University filed Critical East China Normal University
Priority to CN202111073604.5A priority Critical patent/CN113797226B/en
Publication of CN113797226A publication Critical patent/CN113797226A/en
Application granted granted Critical
Publication of CN113797226B publication Critical patent/CN113797226B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/22—Boron compounds
    • 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
    • A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6921—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere
    • A61K47/6923—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a particulate, a powder, an adsorbate, a bead or a sphere the form being an inorganic particle, e.g. ceramic particles, silica particles, ferrite or synsorb
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A61K9/5107—Excipients; Inactive ingredients
    • A61K9/5115—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y30/00—Nanotechnology for materials or surface science, e.g. nanocomposites
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y40/00—Manufacture or treatment of nanostructures
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B33/00—Silicon; Compounds thereof
    • C01B33/113—Silicon oxides; Hydrates thereof
    • C01B33/12—Silica; Hydrates thereof, e.g. lepidoic silicic acid
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B33/00—Silicon; Compounds thereof
    • C01B33/113—Silicon oxides; Hydrates thereof
    • C01B33/12—Silica; Hydrates thereof, e.g. lepidoic silicic acid
    • C01B33/18—Preparation of finely divided silica neither in sol nor in gel form; After-treatment thereof
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
    • C01B6/00—Hydrides of metals including fully or partially hydrided metals, alloys or intermetallic compounds ; Compounds containing at least one metal-hydrogen bond, e.g. (GeH3)2S, SiH GeH; Monoborane or diborane; Addition complexes thereof
    • C01B6/06—Hydrides of aluminium, gallium, indium, thallium, germanium, tin, lead, arsenic, antimony, bismuth or polonium; Monoborane; Diborane; Addition complexes thereof
    • C01B6/10—Monoborane; Diborane; Addition complexes thereof
    • C01B6/13—Addition complexes of monoborane or diborane, e.g. with phosphine, arsine or hydrazine
    • C—CHEMISTRY; METALLURGY
    • C01—INORGANIC CHEMISTRY
    • C01P—INDEXING SCHEME RELATING TO STRUCTURAL AND PHYSICAL ASPECTS OF SOLID INORGANIC COMPOUNDS
    • C01P2004/00—Particle morphology
    • C01P2004/01—Particle morphology depicted by an image
    • C01P2004/04—Particle morphology depicted by an image obtained by TEM, STEM, STM or AFM

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Nanotechnology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Inorganic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Epidemiology (AREA)
  • Physics & Mathematics (AREA)
  • General Physics & Mathematics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biomedical Technology (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • Neurology (AREA)
  • Biotechnology (AREA)
  • Manufacturing & Machinery (AREA)
  • Composite Materials (AREA)
  • General Engineering & Computer Science (AREA)
  • Neurosurgery (AREA)
  • Biophysics (AREA)
  • Materials Engineering (AREA)
  • Molecular Biology (AREA)
  • Medical Informatics (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Ceramic Engineering (AREA)
  • Optics & Photonics (AREA)
  • Silicon Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to ammonia borane/silicon spheres/mesoporous silicon dioxide nano composite particles and a preparation method and application thereof, wherein the chemical formula of the nano composite particles is AB/SiO2@mSiO2The preparation method is characterized in that a silicon dioxide ball is used as a substrate, mesoporous silicon dioxide is used as a shell, and a gas prodrug capable of generating hydrogen in an acidic microenvironment is loaded. The nano-composite particles are used as drug carriers, imaging diagnosis, gas therapy, anti-inflammation, synergistically enhance nerve function recovery, reduce fibrotic scarring, and promote nerve regeneration by inhibiting oxidative stress. Compared with the prior art, the AB/SiO of the invention2@mSiO2The nano composite particles have novel structures, have wide application prospects in aspects of gas prodrug loading, controllable release of gas, ultrasonic imaging and diagnosis and treatment of spinal cord injury, can transmit the gas prodrug to an injury pathological change part, diagnose and observe treatment conditions in real time through imaging, comprehensively adjust oxidation and inflammation imbalance in a microenvironment and effectively treat the spinal cord injury in a visualized manner.

Description

Ammonia borane/silicon ball/mesoporous silicon dioxide nano composite particle and preparation and application thereof
Technical Field
The invention belongs to the technical field of carriers for diagnosing and treating oxidative stress related diseases, and relates to ammonia borane/silicon spheres/mesoporous silicon dioxide nano composite particles, and preparation and application thereof.
Background
Spinal Cord Injury (SCI) is a devastating disease of the central nervous system that often results in refractory neurological dysfunction, loss of sensory and autonomic function to varying degrees that can lead to paralysis, and even death in the critically ill. Has the characteristics of complicated injury, long treatment and nursing period, high treatment cost, poor clinical prognosis and the like, not only causes health loss and quality of life pressure for individuals and families, but also causes great burden to health systems and social economy due to productivity loss and high nursing cost. However, the incidence of SCI continues to increase as the population ages and the use of motor vehicles continues to increase and become widespread. At present, no effective prevention and treatment means exist, and the method is a great medical problem facing the world. At the same time, the wide interest of bio-gaseous molecules, such as Nitric Oxide (NO), hydrogen (H) has been raised due to their high selectivity and low systemic toxicity, compared to highly cytotoxic pharmacotherapeutic agents2) Carbon monoxide (CO) and hydrogen sulfide (H)2S). The gas molecules existing in the nature or in the organism can affect the metabolism and maintain the steady state of the physiological functions of human beings. Wherein H2Because of its green, negligible side effects, hydrogen therapy has received extensive attention in the field of anti-inflammatory therapy as an emerging, promising therapeutic strategy against oxidative stress. In addition to being bio-permeable and bio-safe, H2It has been shown that ROS-induced cytotoxic and inflammatory responses in cells can be selectively mitigated, with important physiological functions for homeostatic regulation, including selective treatment of diseased cells and protection of normal cells. Thus, H2Are proposed as treatments for cancer and central nervous system injury. Inhalation H2Gas and drug delivery H-rich2Has been shown to protect neurons from SCI-induced apoptosis and protect mitochondrial structures, inhibiting reactive astrocytosis. However, how to construct nanoparticles incorporating gaseous molecules to achieve the damaged region H2The controllable release and the sufficient concentration of the active ingredients are problems to be solved urgently.
At present, an integrated carrier which integrates imaging diagnosis, pH response and gas treatment and realizes efficient antioxidant stress diagnosis and treatment is urgently needed.
Chinese patent application No. 201610315917.X discloses an amino-modified Fe with mesoporous structure3O4@SiO2@mSiO2Preparation and application of composite particles and Fe with mesoporous structure3O4@SiO2@mSiO2The preparation method of the composite particles comprises the following steps: mixing Fe3O4@SiO2Dispersing the powder in ethanol, deionized water, ammonia water andobtaining a sol solution from the mixed solution of the template agent; then tetraethyl orthosilicate is dripped to prepare Fe with mesoporous structure3O4@SiO2@mSiO2And (3) compounding the particles. However, the technical solution of this patent has the following technical problems: 1) fe3O4@SiO2@mSiO2The synthetic process of the composite particles is long and is not beneficial to the industrial scale-up operation. 2) Fe3O4@SiO2@mSiO2The intermediate layer of the composite particles is Fe3O4The core is coated with a layer of SiO2A layer of mesoporous SiO is coated on the base of the layer2Layer of SiO in between2The layer has no essential purpose and can be directly in Fe3O4Directly growing mesoporous SiO on the basis2The layers are synthesized in a simple manner. 3) Mesoporous SiO2Has limited adsorption capacity and limits Fe3O4@SiO2@mSiO2The composite particle is applied to the heavy metal adsorption in the water treatment technology.
The Chinese invention patent with the application number of 201711453083.X discloses an acid-response hydrogen-releasing nano-drug and a preparation method thereof, which are used for treating tumors. The anti-tumor drug is AB @ MSN nano-drug, and comprises a mesoporous silica carrier and H loaded in the mesoporous silica carrier and having an acid response characteristic2A prodrug. However, the technical solution of this patent has the following technical problems: 1) the particle size of the AB @ MSN nano-drug is about 50nm, and the AB @ MSN nano-drug with the size is injected into a human body and is easily absorbed by the liver and cannot exert the drug effect of the AB @ MSN nano-drug, so that the medical application is limited to a great extent; 2) CTAC can not be well removed by extracting the surfactant CTAC three times in total by using an ethanol solution of hydrochloric acid, and the formation of a mesoporous structure is further influenced; 3) whether hydrogen alone really has a good anticancer effect is being questioned and whether the observed inhibition of cancer growth is another secondary factor to be further investigated.
Disclosure of Invention
The invention aims to overcome the technical problems in the prior art, and provides ammonia borane/silicon spheres/mesoporous silica nano composite particles which are simple, convenient and mild in synthesis conditions, convenient in raw material source, controllable in size and pore diameter, excellent in acid response effect, free of biotoxicity and excellent in stability.
The invention also aims to provide a preparation method of the ammonia borane/silicon ball/mesoporous silica nano composite particle.
The invention further aims to provide application of the ammonia borane/silicon ball/mesoporous silica nano composite particle.
The patent starts from the oxidation resistance of hydrogen, finds another brand-new nano composite particle, inhibits oxidative stress reaction and promotes the treatment of nerve regeneration, and has good clinical transformation significance.
The purpose of the invention can be realized by the following technical scheme:
the ammonia borane/silicon ball/mesoporous silicon dioxide nano composite particle has a chemical formula of AB/SiO2@ mSiO2, which is a gas prodrug ammonia borane loaded with solid silica spheres as core and mesoporous silica as shell and capable of generating hydrogen in acidic environment.
Preferably, the diameter of the nanocomposite particle is 180-230 nm. More preferably 220 nm.
The preparation method of the ammonia borane/silicon ball/mesoporous silicon dioxide nano composite particle comprises the following steps:
1) preparing monodisperse solid silicon Spheres (SiO) by taking tetraethoxysilane as a silicon source through hydrolysis reaction in alkaline environment2)；
2) In the presence of a template agent, the SiO prepared in the step 1)2Coating a layer of thick silicon oxide on the surface of the nano-particles to prepare SiO2@SiO2Nanoparticles;
3) SiO prepared in the step 2)2@SiO2Nano particles form SiO with mesoporous structure by removing template agent through methanol2@mSiO2A nanoparticle;
4) SiO prepared in the step 3)2@mSiO2Nanometer particle loaded gas prodrug Ammonia Borane (AB), namely AB/SiO is prepared2@mSiO2A nanometer medicinal preparation.
Preferably, the first and second electrodes are formed of a metal,
the step 1) adopts a sol-gel method, and the process steps of the sol-gel method are as follows: in a reaction vessel, according to the measurement of the reaction process of tetraethyl orthosilicate and water, ethanol is used as a solvent, water is used as a medium to be mixed, ammonia water is used as a catalyst, the mixture is stirred for 8 to 25min at the temperature of between 20 and 40 ℃, then a certain amount of tetraethyl orthosilicate is dripped to carry out hydrolytic polymerization reaction, the mixture is stirred for 1 to 2.5h in a water bath at the temperature of between 20 and 40 ℃, then the final product is dispersed in a certain amount of water after alcohol washing and water washing, and finally, the monodisperse solid SiO is obtained by vacuum drying2Particles; the mass ratio of the ammonia water, the ethanol, the deionized water and the tetraethyl orthosilicate is 1-2.5: 40: 5-10: 1-4. More preferably, the dosage ratio of the ammonia water, the ethanol, the deionized water and the tetraethyl orthosilicate is 3.2 mL: 74 mL: 15mL of: 2.5-4.5 mL.
The specific process steps of the step 2) are as follows: adding template agent and triethanolamine into a certain amount of ultrapure water, stirring for 0.5-1.5h, and heating to 78-90 deg.C; then adding the SiO prepared in the step 1) and dispersed in deionized water2Stirring the nano particles and tetraethyl orthosilicate for 0.5-2h at 78-90 ℃ to wrap a thick layer of silicon dioxide, and washing and centrifuging to obtain SiO2@SiO2Nanoparticles; the template can be Cetyl Trimethyl Ammonium Chloride (CTAC) or Cetyl Trimethyl Ammonium Bromide (CTAB); the template agent, triethanolamine and SiO dispersed in deionized water2The dosage ratio of the nano particles to the tetraethyl orthosilicate is 0.8-1.5 g: 0.1-0.8 g: 5-15 mL: 1.5-2.5 mL. More preferably, the template agent, triethanolamine and SiO dispersed in deionized water2The dosage ratio of the nano particles to the tetraethyl orthosilicate is 1-1.5 g: 0.2-0.3 g: 8-15 mL: 1.5-2 mL.
The process for constructing the mesoporous structure by using the methanol template removal agent in the step 3) comprises the following steps: taking the obtained SiO2@SiO2Stirring nano particles with a certain amount of methanol containing 1% NaCl at 40-65 deg.C for 4-12h, centrifuging, washing with water for three times, and dispersing in water to obtain SiO with mesoporous structure2@mSiO2Composite nanoparticles.The amount of the methanol with 1% of NaCl can be determined according to SiO2The weight of the shell and the reaction time.
The process of the step 4) comprises the following steps: dissolving ammonia borane in SiO prepared in step 3)2@mSiO2Stirring the composite nano particle buffer solution for 30 to 40 hours at room temperature, then centrifugally washing the solution, and dispersing the solution in water to obtain the AB/SiO2@mSiO2Composite nanoparticles; the SiO2@mSiO2The mass concentration of the composite nano particles in the deionized water is 10-30mg/mL (preferably 20 mg/mL); the ammonia borane and SiO2@mSiO2The mass ratio of the composite nano particles is 4-15: 1 (preferably in a mass ratio of 4.5-7: 1).
The invention AB/SiO2@mSiO2The nano composite medicine is used as a medicine carrier, can efficiently encapsulate the gas prodrug, and has wide application prospect in the aspect of gas treatment. Meanwhile, the composition has strong acid responsiveness, can effectively and accurately treat spinal cord injury efficiently under pH sensitive release or ultrasonic controllable release at a lesion injury part, synergistically enhance nerve function recovery, reduce fibrotic scar formation, and promote nerve regeneration by inhibiting oxidative stress reaction.
Compared with the existing numerous nano-carriers, the AB/SiO of the invention2@mSiO2The research of the nano composite particle is more advanced because the nano composite particle is constructed based on SiO2，SiO2Has the advantages of controllable pore size, easy surface modification, no toxicity, no harm, good biocompatibility and the like, provides brand new thought and concept for the design of inorganic materials on the medical nano scale, and simultaneously, has the advantages of high compatibility and the like2The surface is modified, and the gas prodrug with biological function is coated, so that the visual treatment of the spinal cord injury can be efficiently and controllably realized.
The difference between the present invention and the prior patent 20165917. X is that: (1) is also mSiO2Is a shell, but the preparation method is completely different. The invention is that the silicon dioxide nanometer particle is used as the base body, a layer of silicon ball is coated outside, then the methanol removes the template agent to form the SiO with the mesoporous structure2@mSiO2。(2)mSiO2The use of (c) is different. The inventionSiO using mesopores2On the one hand, the use of SiO2Good biocompatibility as an excellent drug delivery system; on the other hand, the mesoporous structure is utilized to carry out good loading of the gas prodrug. (3) The application of nanoparticles is different. The nanoparticles of the present invention are useful for loading gaseous prodrugs, releasing hydrogen in an acidic environment for use as anti-inflammatory therapies.
Compared with the prior art, the invention has the following technical effects:
1) AB/SiO prepared by the invention2@mSiO2The nano composite particle reaction device and conditions are simple and convenient, the required raw materials have wide sources, the cost is low, the biocompatibility is good, in particular to the gas prodrug ammonia borane which has high hydrogen content (196 gH)2/kg), has good water solubility and dispersibility, is not biologically toxic and is stable to storage under normal conditions. The preparation period of the nano-carrier is greatly shortened, and finally, the nano-particles have high stability and are convenient to store;
2) AB/SiO prepared by the method of the invention2@mSiO2The particle size of the nano composite particles is 180-230nm, so that high permeability of a lesion and injury part can be well realized after the nano medicine enters an animal body.
3) AB/SiO prepared by the method of the invention2@mSiO2The mesoporous structure of the nano composite particles can better ensure the loading of the gas prodrug and can better realize anti-inflammatory treatment. AB/SiO prepared by the invention2@mSiO2The nano composite particles have flexible and adjustable pore size distribution, can well load gas prodrug Ammonia Borane (AB), simultaneously have pH response release and ultrasonic controllable drug release performances, and can accurately release H at lesion and injury parts2The effect of relieving spinal cord injury is achieved, and meanwhile, the nerve function recovery is synergistically enhanced, and the nerve regeneration is promoted.
From AB/SiO of example 12@mSiO2The low-power and high-power TEM results of the particle size of the composite nanoparticles are shown in FIG. 1, and it can be seen that AB/SiO2@mSiO2The particle size of the composite nano particle is about 220nm, and the particle size is very suitable for cell experiments and in vivo treatmentIn (1).
From AB/SiO of example 12@mSiO2H of composite nanoparticle2Release results fig. 2, it can be seen that there is essentially no significant H at pH 7.42And (4) releasing. Apparently, in an acidic environment H2The release rate is faster. Shows that under physiological conditions, AB/SiO2@mSiO2The composite nanoparticles cannot be decomposed into H2While acidic conditions can significantly promote H2And (4) releasing.
From AB/SiO of example 12@mSiO2The cytotoxicity evaluation results of the composite nanoparticles are shown in FIG. 3, and it can be seen that AB/SiO2@mSiO2The composite nanoparticles still have no obvious cytotoxicity at the concentration of 400 mu g/mL.
From AB/SiO of example 12@mSiO2The results of the evaluation of cell internalization of the composite nanoparticles are shown in FIG. 4, and it can be seen that AB/SiO2@mSiO2The composite nanoparticles continued to accumulate in the nucleus after 4 hours after incubation with the cells.
From AB/SiO of example 12@mSiO2In vivo antioxidant level evaluation results of the composite nanoparticles are shown in FIG. 5, and it can be seen that AB/SiO2@mSiO2The DHE staining intensity can be obviously reduced after the intervention of the composite nano particles, which shows that the AB/SiO2@mSiO2The compound nano particles effectively eliminate the excessive accumulation of ROS and relieve the spinal cord injury.
From AB/SiO of example 12@mSiO2In vivo nerve repair evaluation results of the composite nanoparticles FIG. 6, it can be seen that AB/SiO2@mSiO2The composite nano particle can obviously increase the expression of MBP protein, NF200 protein and beta iii-tubulin, and proves that AB/SiO2@mSiO2Has remarkable effects in preserving neurons and promoting axon regeneration, thereby promoting recovery of nerve function.
From AB/SiO of example 12@mSiO2The in vivo toxicity test result of the composite nanoparticle is shown in FIG. 7, and it can be seen that AB/SiO2@mSiO2The composite nano-drug has good biocompatibility and no obvious effectBiological toxicity, and is very promising for repairing spinal cord injury.
Drawings
FIG. 1 is a diagram of SiO in example 1 of the present invention2、SiO2@mSiO2TEM spectrum of nano particle, wherein a and b are dSiO respectively2The low-power TEM pattern and the high-power TEM pattern of the nano particles, c and d are respectively SiO2@mSiO2A low power TEM spectrum and a high power TEM spectrum of the nanoparticles;
FIG. 2 shows AB/SiO in example 1 of the present invention2@mSiO2pH-responsive hydrogen generation and release of composite nanoparticles;
FIG. 3 shows AB/SiO in example 1 of the present invention2@mSiO2Mouse microglia (Bv2 cell) survival rate of the composite nanoparticles at different concentrations;
FIG. 4 shows AB/SiO in example 1 of the present invention2@mSiO2In vitro confocal fluorescence images of Bv2 cells incubated for 2h and 4h with the composite nanoparticles. The scale bar is 50 μm;
FIG. 5 shows AB/SiO in example 1 of the present invention2@mSiO2The composite nanoparticles reduced the oxidative stress level of the injured spinal cord in SCI rats, DHE staining showing ROS production in 2dpi per group.
FIG. 6 shows AB/SiO in example 1 of the present invention2@mSiO2The composite nanoparticles affect western blot images and semi-quantitative levels of expression of Myelin Basic Protein (MBP), β iii-tubulin, and neurofilament protein-200 (NF200) in longitudinal spinal cord tissue.
FIG. 7 shows AB/SiO in example 1 of the present invention2@mSiO2Pathology H of major organs (including heart, liver, spleen, lung and kidney) collected 3 days after injection and untreated in vivo with composite nanoparticles&E staining the image.
Detailed Description
The invention is described in detail below with reference to the figures and specific embodiments.
The purchase sources of reagents involved in the examples of the present invention are described below:
tetraethyl orthosilicate, ethanol, ammonia, cetyltrimethylammonium chloride, triethanolamine, sodium chloride, methanol, and ammonia borane were all purchased from Shanghai Michelin Biotech. All antibodies were purchased from eboantibody (shanghai) trade ltd. BCA protein assay kit was purchased from siemer feishel technologies, fluorescent staining reagents and peroxidase-conjugated secondary antibodies were purchased from the pica biotechnology institute, and ECL kit was purchased from merck. All animal experimental protocols were approved by the ethical committee of the university of east china and were carried out according to the guidelines of the animal care and ethical committee of the university of east china.
Example 1
In this example, ammonia borane/silicon spheres/mesoporous silica nanocomposite particles (AB/SiO)2@mSiO2) The composite structure nano particle is prepared with solid silicon ball as core and silicon oxide as shell and methanol to eliminate template agent to obtain mesoporous SiO2@mSiO2And then loading the ammonia borane small molecule prodrug.
(1) The preparation method of the ammonia borane/silicon sphere/mesoporous silicon dioxide nano composite particle comprises the following steps:
(1-1) silica dSiO2Preparation of nanoparticles: adding 74mL of ethanol, 15mL of water and 3.2mL of ammonia water into a 100mL single-mouth bottle according to the measurement of the reaction process of tetraethyl orthosilicate and water, mixing, stirring for 20min at 30 ℃, then dripping 2.8mL of tetraethyl orthosilicate for hydrolytic polymerization reaction, stirring for 2h in a water bath at 30 ℃, then washing for 2 times by centrifugal alcohol and 1 time by water, dispersing the final product in water, and finally drying in vacuum to obtain monodisperse SiO2Particles;
(1-2) nanoparticle SiO2@SiO2The preparation of (1): the process of the step (2) comprises the following steps: to 50mL of ultrapure water, 1g of cetyltrimethylammonium chloride (CTAC) and 0.3g of Triethanolamine (TEA) were added, stirred for 1 hour, and heated to 80 ℃. Then, the above-mentioned 10mL of SiO dispersed in deionized water was added2Stirring the nano particles and 1.8mL tetraethyl orthosilicate for 1h at 80 ℃ to wrap a thick layer of silicon dioxide, washing with water, centrifuging, and dispersing in deionized water to obtain SiO2@SiO2Nanoparticles;
(1-3) nanoparticle SiO2@mSiO2The preparation of (1): taking the monodisperse SiO dispersed in deionized water2@SiO2Adding 50mL of methanol solution containing 1% NaCl into the nano particles to remove the template agent CTAC, stirring for 6h, then centrifugally washing for three times, and dispersing in water to obtain SiO with a mesoporous structure2@mSiO2Composite nanoparticles;
(1-4) nanocomposite particles AB/SiO2@mSiO2The preparation of (1): 180mg of ammonia borane was weighed and dissolved in 2mL (20mg/mL) of SiO2@mSiO2Stirring for 36h at room temperature in the composite nano particle buffer solution, and then washing for three times by centrifugal water to obtain AB/SiO2@mSiO2The composite nano particles are stored at 4 ℃ for later use.
(2)AB/SiO2@mSiO2The particle size of the composite nanoparticles is as follows: the low power and high power TEM are shown in FIG. 1, respectively, and AB/SiO can be seen2@mSiO2The particle size of the composite nanoparticle is about 220nm, and the particle size is very suitable for cell experiments and in vivo treatment.
(3)AB/SiO2@mSiO2H of composite nanoparticle2Releasing: by gas chromatography to obtain different volumes of H2The standard curve of (2). Buffers with pH 7.4 (normal tissue environment) and pH 6.6 (spinal cord injury microenvironment) were prepared separately and placed in a 100mL reactor equipped with a stirring device. Argon deoxygenation at room temperature for 40min, after removal of excess gas, 5mg AB/SiO was added to the reactor2@mSiO2A nanocomposite particle. Subsequently, 1mL of gas was withdrawn from the vessel at various time points and H was measured using a GC2060 system2The amount of (a) released.
As can be seen from fig. 2, there was substantially no significant H at pH 7.42And (4) releasing. Apparently, in an acidic environment H2The release rate is faster. Shows that under physiological conditions, AB/SiO2@mSiO2The composite nanoparticles cannot be decomposed into H2While acidic conditions can significantly promote H2And (4) releasing.
(4)AB/SiO2@mSiO2Composite nanoEvaluation of rice grain cytotoxicity: bv2 cells were seeded in 96-well plates with different concentrations of AB/SiO2@mSiO2After 24h incubation, cell viability was determined by standard Methylthiazoletetrazole (MTT) method (see FIG. 3 for results).
As can be seen from FIG. 3, AB/SiO2@mSiO2The composite nanoparticles still have no obvious cytotoxicity at the concentration of 400 mu g/mL.
(5)AB/SiO2@mSiO2Evaluation of cellular internalization of composite nanoparticles: in terms of in vitro cellular uptake, Bv2 cells were cultured in 12-well plates for 24 hours. Then, using a solution containing Cy5-AB/SiO2@mSiO2Fresh medium (500. mu.g/ml) was further incubated for 2h and 4 h. Followed by fixation with 4% paraformaldehyde solution for 15 minutes. Nuclei were then stained with Hoechst 33342 for 20min and washed 3 times with PBS. Finally, fluorescence images of the cells were observed using a Confocal Laser Scanning Microscope (CLSM).
As can be seen from FIG. 4, Cy5-AB/SiO2@mSiO2The panel showed red fluorescence due to Cy5, while the nuclei showed blue fluorescence due to Hoechst. After incubation for 2h, a relatively weak red fluorescence appeared in the cytoplasm, indicating that the complex nanoparticles were phagocytosed by Bv2 cells. With increasing incubation time, AB/SiO2@mSiO2The composite nanoparticles continued to accumulate in the nucleus after 4 hours after incubation with the cells. Indicating that more composite nanoparticles entered Bv2 cells. That is, AB/SiO2@mSiO2The composite nanoparticle can be delivered into a cell.
(6)AB/SiO2@mSiO2Evaluation of in vivo antioxidant levels of composite nanoparticles: 220g female rats are selected to establish a spinal cord injury model, and then the rats are randomly divided into the following groups: spinal cord injury groups (SCI groups) to which 10. mu.l of PBS was intrathecally administered 1 day (1dpi), 3dpi, and 7dpi after injury, and 10. mu.l of SiO2@mSiO2(500. mu.g/ml) of group (SiO2@mSiO2Group) and administration of 10. mu.l AB/SiO2@mSiO2(500. mu.g/ml) of group (AB/SiO2@mSiO2Groups). Spinal cord tissue from a 0.5 cm long area from the center of the lesion was harvested 7 dpi.Frozen sections were prepared and stained with the ROS fluorescent probe Dihydroethidium (DHE).
As can be seen in FIG. 5, tissue DHE fluorescence expression is evident in the SCI group, indicating high ROS levels in spinal cord injury, SiO alone2@mSiO2Group intervention did not affect DHE fluorescence expression. And AB/SiO2@mSiO2The DHE staining intensity can be obviously reduced after the intervention of the composite nano particles, which shows that the AB/SiO2@mSiO2The compound nano particles effectively eliminate the excessive accumulation of ROS and relieve the spinal cord injury.
(7)AB/SiO2@mSiO2In vivo nerve repair evaluation of composite nanoparticles: 120 female rats (-220 g) were selected to build a spinal cord injury model, and then the rats were randomly divided into four groups: only laminectomy group (sham group, n 30); spinal cord injury group injected with PBS only (SCI group, n-30), administration with SiO2@mSiO2Group of composite nanoparticles (SiO)2@mSiO2Group, n ═ 30) and AB/SiO2@mSiO2Group of composite nanoparticles (AB/SiO)2@mSiO2Group, n ═ 30). SCI group, SiO2@mSiO2Group AB/SiO2@mSiO2Groups were intrathecally administered with 10. mu.l of PBS and SiO at 1 day (1dpi), 3dpi, and 7dpi after injury2@mSiO2(500. mu.g/ml) and AB/SiO2@mSiO2(500. mu.g/ml) composite nanoparticles. Spinal cord tissue from a 0.5 cm long area from the center of the lesion was harvested 7 dpi. Total protein was isolated by homogenizing the tissue in cold lysis buffer. After quantifying the protein concentration with the BCA protein assay kit, the proteins were separated by SDS-PAGE and transferred onto PVDF membrane. PVDF membrane was blocked with 5% Bovine Serum Albumin (BSA) and incubated with primary antibody. After washing the membranes, incubated with species-matched peroxidase-conjugated secondary antibodies for 2 hours at room temperature, ECL kit was used to visualize immunoreactive bands. Finally, the band density was calculated using ImageJ software.
MBP protein, neurofilament protein-200 (NF200) and β iii-tubulin are indicators of damaged area neurons and regenerated axons after SCI. As can be seen from FIG. 6, MBP protein, NF200 egg, of SCI groupSignificantly lower expression of white and beta iii-tubulin, SiO alone2@mSiO2Group intervention did not affect the expression of these proteins. However, with PBS and SiO2@mSiO2Group comparison, AB/SiO2@mSiO2The composite nano particle can obviously increase the expression of MBP protein, NF200 protein and beta iii-tubulin, and proves that AB/SiO2@mSiO2Has remarkable effects in preserving neurons and promoting axon regeneration, thereby promoting recovery of nerve function.
(8)AB/SiO2@mSiO2In vivo toxicity testing of composite nanoparticles: SD rats weighing about 220g were obtained from Shanghai laboratory animal center of Chinese academy of sciences. Injecting AB/SiO through tail vein2@mSiO2(dispersed in 100. mu.L of physiological saline) and the same volume of physiological saline was injected as a control group. After 3 days, the mice were sacrificed, and their main internal organs (heart, liver, spleen, lung and kidney) were collected and observed under an optical microscope for H&E staining the tissue sections.
As can be seen from FIG. 7, the tissue sections H of the experimental group and the control group&E staining did not show significant organ damage or inflammatory lesions, which further indicates AB/SiO2@mSiO2The composite nano-drug has good biocompatibility and no obvious biotoxicity, and is very promising for repairing spinal cord injury.
Example 2
The preparation method of the ammonia borane/silicon spheres/mesoporous silica nanocomposite particle of the embodiment is basically the same as that of the embodiment 1, except that:
in step (1-1), the amount of tetraethyl orthosilicate added was 2.5 mL.
In the step (1-2), Triethanolamine (TEA) was added in an amount of 0.2g, and monodisperse SiO was dispersed in deionized water2The amount of nanoparticles added was 8 mL.
In step (1-3), 40mL of a 1% NaCl solution in methanol was added.
In the step (1-4), the ammonia borane is added in an amount of 200mg and SiO2@mSiO2The composite nanoparticles were 1.5 mL.
The detection result and performance of the ammonia borane/silicon spheres/mesoporous silica nanocomposite particle obtained in this example 2 are substantially the same as those of example 1.
Example 3
The preparation method of the ammonia borane/silicon spheres/mesoporous silica nanocomposite particle of the embodiment is basically the same as that of the embodiment 1, except that:
in step (1-1), the amount of tetraethyl orthosilicate added was 4.5 mL.
In the step (1-2), cetyltrimethylammonium chloride was added in an amount of 1.5g, and the monodisperse SiO solution was dispersed in deionized water2The amount of nanoparticles added was 15 mL.
In step (1-3), the amount of 1% NaCl in methanol was 65 mL.
In the step (1-4), the ammonia borane is added in an amount of 300mg and SiO2@mSiO2The composite nanoparticles were 2.5 mL.
The detection result and performance of the ammonia borane/silicon spheres/mesoporous silica nanocomposite particle obtained in this example 3 are substantially the same as those of example 1.
The embodiments described above are described to facilitate an understanding and use of the invention by those skilled in the art. It will be readily apparent to those skilled in the art that various modifications to these embodiments may be made, and the generic principles described herein may be applied to other embodiments without the use of the inventive faculty. Therefore, the present invention is not limited to the above embodiments, and those skilled in the art should make improvements and modifications within the scope of the present invention based on the disclosure of the present invention.

Claims (8)

1. The ammonia borane/silicon ball/mesoporous silicon dioxide nano composite particle is characterized in that the chemical formula of the nano composite particle is AB/SiO2@ mSiO2, which is a gas prodrug ammonia borane loaded with solid silica spheres as core and mesoporous silica as shell and capable of generating hydrogen in acidic environment.
2. The ammonia borane/silicon sphere/mesoporous silica nanocomposite particle according to claim 1, wherein the diameter of the nanocomposite particle is 180-230 nm.
3. The method for preparing ammonia borane/silicon spheres/mesoporous silica nanocomposite particles according to claim 1, which specifically comprises the following steps:
1) preparing monodisperse solid silicon dioxide SiO by taking tetraethoxysilane as raw material through hydrolysis reaction in alkaline environment2A nanoparticle;
2) in a template agent solution, the SiO prepared in the step 1)2Coating a layer of thick silicon oxide on the surface of the nano-particles to prepare SiO2@SiO2Nanoparticles;
3) SiO prepared in the step 2)2@SiO2The nano particles remove the template agent through methanol to construct SiO with a mesoporous structure2@mSiO2A nanoparticle;
4) SiO prepared in the step 3)2@mSiO2The nano particles are coated with gas prodrug ammonia borane AB to prepare AB/SiO2@mSiO2Composite nanoparticles.
4. The method for preparing ammonia borane/silicon spheres/mesoporous silica nanocomposite particles according to claim 3, wherein a sol-gel method is adopted in the step 1), and the process steps of the sol-gel method are as follows: in a reaction vessel, according to the measurement of the reaction process of tetraethyl orthosilicate and water, ethanol is used as a solvent, water is used as a medium to be mixed, ammonia water is used as a catalyst, the mixture is stirred for 8 to 25min at the temperature of between 20 and 40 ℃, then a certain amount of tetraethyl orthosilicate is dripped to carry out hydrolytic polymerization reaction, the mixture is stirred for 1 to 2.5h in a water bath at the temperature of between 20 and 40 ℃, then the final product is dispersed in a certain amount of water after alcohol washing and water washing, and finally, the monodisperse solid SiO is obtained by vacuum drying2Particles; the mass ratio of the ammonia water, the ethanol, the deionized water and the tetraethyl orthosilicate is 1-2.5: 40: 5-10: 1-4.
5. The ammonia boron of claim 3The preparation method of the alkane/silicon spheres/mesoporous silica nano composite particles is characterized in that the specific process steps of the step 2) are as follows: adding template agent and triethanolamine into a certain amount of ultrapure water, stirring for 0.5-1.5h, and heating to 78-90 deg.C; then adding the SiO prepared in the step 1) and dispersed in deionized water2Stirring the nano particles and tetraethyl orthosilicate for 0.5-2h at 78-90 ℃ to wrap a thick layer of silicon dioxide, and washing and centrifuging to obtain SiO2@SiO2Nanoparticles;
the template agent is Cetyl Trimethyl Ammonium Chloride (CTAC) or Cetyl Trimethyl Ammonium Bromide (CTAB); the dosage ratio of the template agent, triethanolamine, SiO2 nano particles dispersed in deionized water and tetraethyl orthosilicate is 0.8-1.5 g: 0.1-0.8 g: 5-15 mL: 1.5-2.5 mL.
6. The method for preparing ammonia borane/silicon spheres/mesoporous silica nanocomposite particles according to claim 3, wherein the process for constructing the mesoporous structure by using the methanol template removal agent in the step 3) comprises the following steps: taking the obtained SiO2@SiO2Stirring nano particles with a certain amount of methanol containing 1% NaCl at 40-65 deg.C for 4-12h, centrifuging, washing with water for three times, and dispersing in water to obtain SiO with mesoporous structure2@mSiO2Composite nanoparticles.
7. The method for preparing ammonia borane/silicon spheres/mesoporous silica nanocomposite particles according to claim 3, wherein the process step of the step 4) is as follows: dissolving ammonia borane in SiO prepared in step 3)2@mSiO2Stirring the composite nano particle buffer solution for 30 to 40 hours at room temperature, then centrifugally washing the solution, and dispersing the solution in water to obtain the AB/SiO2@mSiO2Composite nanoparticles;
the SiO2@mSiO2The mass concentration of the composite nano particles in deionized water is 10-30 mg/mL; the ammonia borane and SiO2@mSiO2The mass ratio of the composite nano particles is 4-15: 1.
8. use of ammonia borane/silicon spheres/mesoporous silica nanocomposite particles according to claim 1 or 2 or ammonia borane/silicon spheres/mesoporous silica nanocomposite particles prepared by the method according to any one of claims 3 to 7 for the preparation of a supported gas prodrug and a gas therapeutic agent for delivery of the gas prodrug to the site of injury for effective treatment of spinal cord injury by modulation of inflammatory imbalance.
CN202111073604.5A 2021-09-14 2021-09-14 Ammonia borane/silicon sphere/mesoporous silica nano composite particle, preparation and application thereof Active CN113797226B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202111073604.5A CN113797226B (en) 2021-09-14 2021-09-14 Ammonia borane/silicon sphere/mesoporous silica nano composite particle, preparation and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202111073604.5A CN113797226B (en) 2021-09-14 2021-09-14 Ammonia borane/silicon sphere/mesoporous silica nano composite particle, preparation and application thereof

Publications (2)

Publication Number Publication Date
CN113797226A true CN113797226A (en) 2021-12-17
CN113797226B CN113797226B (en) 2023-09-19

Family

ID=78895197

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202111073604.5A Active CN113797226B (en) 2021-09-14 2021-09-14 Ammonia borane/silicon sphere/mesoporous silica nano composite particle, preparation and application thereof

Country Status (1)

Country Link
CN (1) CN113797226B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114886916A (en) * 2022-02-15 2022-08-12 中国科学院上海硅酸盐研究所 Hydrolysis hydrogen production nano reactor and preparation method and application thereof

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102275936A (en) * 2011-06-09 2011-12-14 华东师范大学 Preparation method of mesoporous spherical Sio2 nanoparticles
CN102836710A (en) * 2012-09-28 2012-12-26 黑龙江大学 Preparation method of silica core/mesoporous silica shell-supported gold nano-particle microspheres
CN103387829A (en) * 2013-07-02 2013-11-13 南京邮电大学 Phosphorescence silica nanometer probe with core shell composition and preparation method thereof
CN103641122A (en) * 2013-11-15 2014-03-19 华东师范大学 Preparation method for multilevel mesoporous silica nanoparticles
CN107790075A (en) * 2016-09-06 2018-03-13 南京理工大学 A kind of magnetic mesoporous SiO of nucleocapsid shell structure2The preparation method of nano-particle
CN108042810A (en) * 2017-12-28 2018-05-18 深圳大学 Hydrogen Nano medication and preparation method thereof is released in a kind of acid response
CN108514884A (en) * 2018-03-29 2018-09-11 延安大学 A kind of magnetic coupling catalysis material and preparation method thereof
CN108821296A (en) * 2018-06-13 2018-11-16 华东师范大学 A kind of preparation method of mesoporous spherical nano Sio 2 particle
CN110302381A (en) * 2019-07-24 2019-10-08 南京工业大学 A kind of mesoporous silica nanospheres and preparation method thereof of surface modification carborane
CN112618514A (en) * 2020-04-13 2021-04-09 华东师范大学 Ammonia borane/hollow mesoporous polydopamine/polyethylene glycol nano composite particle and preparation and application thereof

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102275936A (en) * 2011-06-09 2011-12-14 华东师范大学 Preparation method of mesoporous spherical Sio2 nanoparticles
CN102836710A (en) * 2012-09-28 2012-12-26 黑龙江大学 Preparation method of silica core/mesoporous silica shell-supported gold nano-particle microspheres
CN103387829A (en) * 2013-07-02 2013-11-13 南京邮电大学 Phosphorescence silica nanometer probe with core shell composition and preparation method thereof
CN103641122A (en) * 2013-11-15 2014-03-19 华东师范大学 Preparation method for multilevel mesoporous silica nanoparticles
CN107790075A (en) * 2016-09-06 2018-03-13 南京理工大学 A kind of magnetic mesoporous SiO of nucleocapsid shell structure2The preparation method of nano-particle
CN108042810A (en) * 2017-12-28 2018-05-18 深圳大学 Hydrogen Nano medication and preparation method thereof is released in a kind of acid response
CN108514884A (en) * 2018-03-29 2018-09-11 延安大学 A kind of magnetic coupling catalysis material and preparation method thereof
CN108821296A (en) * 2018-06-13 2018-11-16 华东师范大学 A kind of preparation method of mesoporous spherical nano Sio 2 particle
CN110302381A (en) * 2019-07-24 2019-10-08 南京工业大学 A kind of mesoporous silica nanospheres and preparation method thereof of surface modification carborane
CN112618514A (en) * 2020-04-13 2021-04-09 华东师范大学 Ammonia borane/hollow mesoporous polydopamine/polyethylene glycol nano composite particle and preparation and application thereof

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
ZHAOKUI JIN ET AL: "Nanocapsule-mediated sustained H2 release in the gut ameliorates metabolic dysfunction-associated fatty liver disease", 《BIOMATERIAL》, vol. 276, pages 12130 *
孙学军: "《氢分子生物学》", 30 April 2013, pages: 164 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114886916A (en) * 2022-02-15 2022-08-12 中国科学院上海硅酸盐研究所 Hydrolysis hydrogen production nano reactor and preparation method and application thereof

Also Published As

Publication number Publication date
CN113797226B (en) 2023-09-19

Similar Documents

Publication Publication Date Title
Jiang et al. Intelligent MoS2–CuO heterostructures with multiplexed imaging and remarkably enhanced antitumor efficacy via synergetic photothermal therapy/chemodynamic therapy/immunotherapy
Fei et al. Targeted GSH-exhausting and hydroxyl radical self-producing manganese–silica nanomissiles for MRI guided ferroptotic cancer therapy
Jin et al. Antitumor immunity triggered by photothermal therapy and photodynamic therapy of a 2D MoS2 nanosheet-incorporated injectable polypeptide-engineered hydrogel combinated with chemotherapy for 4T1 breast tumor therapy
CN107349211B (en) Hollow MnO2Composite nano material, preparation method and application thereof
Li et al. Understanding the mechanisms of silica nanoparticles for nanomedicine
CN113384555B (en) Protein-coated copper-based nanocrystalline medicament, and preparation method and application thereof
US11364312B2 (en) Platinum sulfide protein nanoparticle having near-infrared photothermal effect and multimodal imaging function, preparation method therefor and application thereof
CN110893237B (en) Application of copper-palladium alloy nanoparticles and autophagy inhibitor in preparation of medicine or kit for killing tumors based on photothermal effect
CN113521098B (en) Platinum (IV) and cRGD modified GA/Fe nano-particle carried doxorubicin and method for targeted therapy of tumors by using same
Dai et al. SiO2-coated magnetic nano-Fe3O4 photosensitizer for synergistic tumour-targeted chemo-photothermal therapy
Shi et al. MRI-guided dual-responsive anti-tumor nanostructures for synergistic chemo-photothermal therapy and chemodynamic therapy
CN112107556A (en) Nanometer medicine containing arsenic and its prepn
CN107049951B (en) Preparation and triple integrated application of thermosensitive liposome carrying hollow gold nanoparticles and tumor therapeutic agent together
Wang et al. Novel bone tumor cell targeting nanosystem for chemo-photothermal therapy of malignant bone tumors
CN113797226B (en) Ammonia borane/silicon sphere/mesoporous silica nano composite particle, preparation and application thereof
CN104288093B (en) Application of the nano drug transdermal preparation in tumour
Kang et al. Flexible human serum albumin nanocapsules to enhance drug delivery and cellular uptake for photodynamic/chemo cancer therapy
Zhou et al. DNA-templated porous nanoplatform towards programmed “double-hit” cancer therapy via hyperthermia and immunogenicity activation
Meng et al. An NIR-II light-responsive nanoplatform for photothermal and enhanced photodynamic synergistic therapy toward drug-resistant bacterial infection and hypoxia relief in subcutaneous wound healing
CN110251672B (en) Nano diagnosis and treatment agent and preparation method and application thereof
Guo et al. The facile formation of hierarchical mesoporous silica nanocarriers for tumor-selective multimodal theranostics
WO2023193389A1 (en) Resveratrol-lecithin nanoparticle, method for preparing same, and use thereof
Shi et al. Functionalized europium-doped hollow mesoporous silica nanospheres as a cell imaging and drug delivery agents
Lin et al. Folic acid-mediated MSNs@ Ag@ Geb multifunctional nanocomposite heterogeneous platform for combined therapy of non-small cell lung cancer
CN114983967B (en) Humic acid-Gd nano-carrier, preparation method and application thereof in drug delivery

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
GR01 Patent grant
GR01 Patent grant