[go: up one dir, main page]

CN111643673A - Tumor-targeted nano-drug simultaneously encapsulating photosensitizer and protein and application thereof - Google Patents

Tumor-targeted nano-drug simultaneously encapsulating photosensitizer and protein and application thereof Download PDF

Info

Publication number
CN111643673A
CN111643673A CN202010653123.0A CN202010653123A CN111643673A CN 111643673 A CN111643673 A CN 111643673A CN 202010653123 A CN202010653123 A CN 202010653123A CN 111643673 A CN111643673 A CN 111643673A
Authority
CN
China
Prior art keywords
drug
nano
tumor
protein
photosensitizer
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
CN202010653123.0A
Other languages
Chinese (zh)
Other versions
CN111643673B (en
Inventor
张晓龙
曾永毅
刘小龙
丁磊
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.)
Mengchao Hepatobiliary Hospital Of Fujian Medical University (fuzhou Hospital For Infectious Diseases)
Original Assignee
Mengchao Hepatobiliary Hospital Of Fujian Medical University (fuzhou Hospital For Infectious Diseases)
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 Mengchao Hepatobiliary Hospital Of Fujian Medical University (fuzhou Hospital For Infectious Diseases) filed Critical Mengchao Hepatobiliary Hospital Of Fujian Medical University (fuzhou Hospital For Infectious Diseases)
Priority to CN202010653123.0A priority Critical patent/CN111643673B/en
Priority to PCT/CN2020/112583 priority patent/WO2022007153A1/en
Publication of CN111643673A publication Critical patent/CN111643673A/en
Application granted granted Critical
Publication of CN111643673B publication Critical patent/CN111643673B/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
    • 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
    • A61K47/54—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 compound
    • A61K47/545—Heterocyclic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/41—Porphyrin- or corrin-ring-containing peptides
    • A61K38/415—Cytochromes
    • 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
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • 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
    • A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
    • A61K41/0071—PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines
    • 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
    • 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
    • A61K47/6927—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 a solid microparticle having no hollow or gas-filled cores
    • A61K47/6929—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 a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
    • 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
    • A61K47/6927—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 a solid microparticle having no hollow or gas-filled cores
    • A61K47/6929—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 a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle
    • A61K47/6931—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 a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer
    • A61K47/6939—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 a solid microparticle having no hollow or gas-filled cores the form being a nanoparticle, e.g. an immuno-nanoparticle the material constituting the nanoparticle being a polymer the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
    • A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
    • A61K49/0036—Porphyrins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K49/00—Preparations for testing in vivo
    • A61K49/001—Preparation for luminescence or biological staining
    • A61K49/0013—Luminescence
    • A61K49/0017—Fluorescence in vivo
    • A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
    • A61K49/0045—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent agent being a peptide or protein used for imaging or diagnosis in vivo
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Nanotechnology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Biochemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Crystallography & Structural Chemistry (AREA)
  • Biomedical Technology (AREA)
  • Physics & Mathematics (AREA)
  • Manufacturing & Machinery (AREA)
  • Pathology (AREA)
  • Radiology & Medical Imaging (AREA)
  • Biotechnology (AREA)
  • Medical Informatics (AREA)
  • General Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Condensed Matter Physics & Semiconductors (AREA)
  • Organic Chemistry (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)

Abstract

The invention discloses a tumor-targeted nano-drug simultaneously encapsulating a photosensitizer and protein and application thereof in preparing an anti-tumor drug. The tumor targeted nano-drug has the characteristics of active targeting of tumor cells and drug release in response of tumor microenvironment, and can realize the cooperative treatment of photodynamic therapy and protein therapy while performing fluorescence imaging, thereby achieving good diagnosis and treatment effects.

Description

Tumor-targeted nano-drug simultaneously encapsulating photosensitizer and protein and application thereof
Technical Field
The invention belongs to the field of biomedicine, and particularly relates to a multifunctional nano-drug which has active targeting property of tumor cells and responsiveness of tumor microenvironment and can be used for fluorescence imaging and realize the combination of photodynamic therapy and protein therapy, a synthetic method and application thereof.
Background
Cancer is one of the leading causes of morbidity and mortality worldwide, and the number of deaths due to cancer has increased rapidly over the past few decades. Small molecule anticancer drugs are one of the mainstream cancer treatments and one of the most commonly used. However, the free form of anticancer drugs may develop multidrug resistance. Thus, scientists have sought other therapeutic agents to circumvent the limitations described above.
Photodynamic therapy (PDT) with non-invasive clinical treatment and intrinsic fluorescence imaging properties has been a promising approach to cancer treatment since the beginning of the 21 st century. Compared to conventional therapies such as radiotherapy, surgery and chemotherapy, PDT has the advantages of repeatable administration, controllable light dose, rapid therapeutic effect and site-directed treatment by local irradiation. PDT is the excitation of Photosensitizers (PSs) with specific wavelength light irradiation to transfer energy to molecular oxygen (O)2) Producing cytotoxic singlet oxygen (1O2) Leading to apoptosis and/or necrosis of the tumor cells. However, the commonly used highly potent PSs are often hydrophobic, resulting in their susceptibility to self-aggregation in aqueous solutions, which not only reduces their PDT efficacy, but also results in inefficient delivery of PSs molecules to the tumor site. In addition, the aggregation of the PSs molecules greatly reduces the PSs molecules and O2Opportunity of contact betweenAnd is not favorable for playing PDT efficacy.
Protein therapy is an emerging cancer treatment and has shown promise in preclinical and clinical trials for highly effective treatments. Compared with traditional chemotherapeutic agents, the protein used in protein therapy may activate apoptosis of tumor cells or block growth signals of tumors. For example, cytochrome c (cyt c) has been found to be involved in the initiation of the mitochondrial apoptotic pathway. In particular, high levels of Cyt c activate caspase and induce DNA fragmentation in the subsequent nucleus, and can be used to circumvent chemotherapy resistance of tumors and improve therapeutic efficacy. However, clinical transformation of proteinaceous anticancer drugs has long been hampered by a series of problems. It is well known that free proteins are highly unstable in biologically relevant environments due to their sensitivity to chemicals, pH changes, temperature changes and enzymatic degradation, while denatured proteins can trigger immune responses and cause adverse health effects. Furthermore, the cellular uptake efficiency of proteins is unsatisfactory due to their size and surface charge.
Meanwhile, a single treatment method often has certain defects in the aspect of treatment effect, and complete treatment of tumors cannot be realized. The advent of nanotechnology opens up new avenues for the development of combined therapeutic modalities for photodynamic therapy and protein therapy. Researches show that the nano-carrier can efficiently deliver the hydrophobic photosensitizer and the protein, improve the uptake of the photosensitizer by tumors and protect the functional integrity of protein drugs in the delivery process, and simultaneously can use the surface engineering technology to increase the material stability and the uptake capacity of target cells. Therefore, the multifunctional nano-drug which has active targeting of tumor cells, response of tumor microenvironment, fluorescence imaging and combination of photodynamic therapy and protein therapy is developed, and has great application prospect in the aspect of improving tumor therapy.
Disclosure of Invention
The invention aims to provide a tumor targeting nano-drug simultaneously encapsulating a photosensitizer and protein and application thereof.
In order to achieve the purpose, the invention adopts the following technical scheme:
one of protection purposes of the invention is a tumor targeting nano-drug simultaneously encapsulating photosensitizer and protein, which is a nano-particle formed by using a metal organic framework material ZIF-8 as a carrier, simultaneously encapsulating a hydrophobic photosensitizer and a protein drug and modifying by using a modifier; the particle size of the nano-particles is 20-400 nm.
The hydrophobic photosensitizer is one or more of chlorin e6 (Ce 6), curcumin, hypericin, protoporphyrin (IX), tetraphenylporphyrin, zinc phthalocyanine and hypocrellin B.
The protein medicine is cytochrome c (Cyt c), carboxypeptidase G2, interferon alpha-2B, ribonuclease, interleukin-10, PD-1 antibody and granzyme B.
The modifier (SA) is one or more of Hyaluronic Acid (HA), polyethyleneimine, dextran, chitosan, fucose, albumin, gelatin, liposome, and polyvinylpyrrolidone.
The second protection purpose of the invention is the preparation method of the tumor targeting nano-drug, which is dimethyl imidazole (2-MIM) and Zn2+Self-assembling into a metal organic framework material ZIF-8, simultaneously synthesizing a hydrophobic photosensitizer and a protein drug in one step to prepare a pre-nano drug, and then utilizing carboxyl and Zn on a modifier2+The coordination function of the compound is used for synthesizing the tumor targeting nano-drug. The method comprises the following specific steps:
1) uniformly mixing a 2-MIM (metal-insulator-metal) aqueous solution, a Protein drug aqueous solution and a hydrophobic photosensitizer solution (dissolving the hydrophobic photosensitizer in N, N-dimethylformamide), stirring and dispersing for 5min, then quickly dropwise adding an aqueous solution containing zinc acetate or zinc nitrate, stirring for 5-60 min (preferably 10 min) at 300-600 r/min (preferably 400 r/min), centrifuging for 5-60 min at 4 ℃ at 8000-14800 r/min, collecting lower-layer precipitates, and centrifuging and washing for multiple times by using water to obtain the front nano drug PS/Protein @ ZIF-8 encapsulated by the metal organic framework; wherein the weight ratio of the hydrophobic photosensitizer to the protein drug to the zinc acetate or the zinc nitrate is 1-20: 1-20: 100 (preferably 7.5: 8: 100), the molar ratio of zinc acetate or nitrate to 2-MIM used being 1: 1 to 200 (preferably 1: 70);
2) dispersing the obtained PS/Protein @ ZIF-8 in water again, slowly dropwise adding a modifier solution under an ultrasonic condition, stirring for 2-6 h in the dark, adding anhydrous ethanol with the volume of 1/10 in a reaction system, centrifugally washing for 20-40 min at 8000-14800 r/min, centrifugally washing for multiple times with water to obtain the targeted nano-drug PS/Protein @ ZIF-8/SA, and storing in the dark at the temperature of 2-8 ℃; wherein the mass ratio of PS/Protein @ ZIF-8 to the modifier in the reaction system is 1: 0.1 to 10 (preferably 1: 1).
The tumor-targeted nano-drug can be targeted to tumor cells, and can be degraded and released in response to pH sensitivity in a tumor microenvironment to realize synergistic treatment of photodynamic therapy and protein therapy.
The invention has the following beneficial effects:
(1) the tumor targeting nano-drug has simple synthesis steps and mild conditions, and does not influence the activity of protein;
(2) the tumor-targeted nano-drug efficiently entraps the hydrophobic photosensitizer and the protein drug through non-covalent effects such as self-assembly, electrostatic effect and the like, so that the damage of covalent modification to the molecular structure of the drug is avoided;
(3) the tumor targeted nano-drug is modified by a modifier, so that the tumor targeted nano-drug can be degraded in response to a tumor micro-acid microenvironment, and the stability of the drug in a physiological environment and the efficient targeted release of the drug in a tumor are realized;
(4) the tumor targeting nano-drug has both photodynamic therapy capability and protein therapy capability, can realize the synergistic treatment of photodynamic therapy and protein therapy through the catalysis and/or treatment effect of protein, and enhances the combined killing capability on tumors.
In summary, the nano-drug can be used for fluorescence imaging at tumor sites and can also be used as a combined therapeutic agent for cancer.
Drawings
FIG. 1 is a transmission electron microscope (A) of nano-drug Ce6/Cyt C @ ZIF-8/HA, a particle size distribution diagram (B), a Zeta potential diagram (C), an ultraviolet-visible light absorption spectrum diagram (D), a fluorescence spectrum diagram (E) excited by Ce6 excitation wavelength, and a fluorescence spectrum diagram (F) excited by FITC excitation wavelength of different nano-drugs.
FIG. 2 is a graph showing the absorption value of DPBF in the range of 300-600 nm as a function of irradiation time under 670 nm laser irradiation (wherein A is Cyt C @ ZIF-8/HA, B is Ce6/Cyt C @ ZIF-8, and C is Ce6/Cyt C @ ZIF-8/HA), and the normalized change of the absorption value at 415 nm (D).
FIG. 3 shows the release of Ce6 (A) and Cyt c (B) as a function of time at different pH values of the nano-drug Ce6/Cyt c @ ZIF-8/HA.
FIG. 4 is a time variation graph (A) of the nano-drug Ce6/Cyt c @ ZIF-8/HA decomposed in the presence of hydrogen peroxide to generate oxygen and a comparison graph (B) of active oxygen generated under normal oxygen and hypoxic conditions.
FIG. 5 is a contrast graph of fluorescence imaging of nano-drug Ce6/Cyt c @ ZIF-8/HA taken up by cells.
FIG. 6 is a contrast graph of fluorescence imaging of different nano-drugs under light and no light conditions to generate reactive oxygen species in cells.
FIG. 7 is a comparison of PI staining fluorescence images of cells treated with different nano-drugs under light and no light.
FIG. 8 shows the results of quantitative cell viability measurements of different nanomedicines after cell treatment under light and no light conditions.
FIG. 9 shows the result of apoptosis detection of different nano-drugs after cell treatment under light and no light.
Detailed Description
In order to make the present invention more comprehensible, the technical solutions of the present invention are further described below with reference to specific embodiments, but the present invention is not limited thereto.
EXAMPLE 1 preparation of tumor-targeting Nanoparticulates
Respectively weighing 2.27 g of 2-MIM, 8 mg of Cyt c (serving as a protein medicament in the implementation) and 6 mg of Ce6 (serving as a photosensitizer in the implementation), respectively dissolving the 2-MIM, the 8 mg of Cyt c and the 6 mg of Ce6 in 8 mL of distilled water, 0.8 mL of distilled water and 0.6 mL of N, N-Dimethylformamide (DMF), and stirring the three materials at 400 r/min in the dark for 5min to fully mix the three materials; weighing 86 mg of zinc acetate, dissolving in 0.8 mL of distilled water, quickly dripping the obtained zinc acetate solution into the reaction solution, stirring at 400 r/min in the dark for 10 min, collecting the reaction solution, centrifuging at 13300 r/min at 4 ℃ for 30 min, collecting the lower-layer precipitate, centrifuging and washing with distilled water for three times, and then suspending in the distilled water to prepare the front nano-drug Ce6/Cyt c @ ZIF-8 solution with the concentration of 2 mg/mL.
Adding an equal volume of 2 mg/mL HA (used as a modifier in the embodiment) aqueous solution into 2 mg/mL pre-nano-drug solution, performing ultrasonic full mixing, then oscillating for 3 hours in the dark at 500 r/min, adding 1/10 volume of absolute ethyl alcohol into a reaction system, centrifuging for 20 minutes at 4 ℃ and 10000 r/min, then centrifuging and washing for three times by using distilled water to obtain Ce6/Cytc @ ZIF-8/HA, re-dispersing in the distilled water, and placing in a refrigerator at 4 ℃ for storage in the dark.
In addition, referring to the above-mentioned methods, ZIF-8/HA (unloaded with photosensitizer and protein drug), Ce6@ ZIF-8/HA (unloaded with protein drug), Cyt c @ ZIF-8/HA (unloaded with photosensitizer), Ce6/Cyt c @ ZIF-8 (without modifier), Ce6@ ZIF-8 (unloaded with protein drug and without modifier) were synthesized separately and used as reference samples together with Ce6, Cyt c, and ZIF-8 for comparative studies.
Example 2:
1. the nano-drug synthesized in example 1 was characterized by tests such as Transmission Electron Microscopy (TEM), nano-particle size and Zeta potential analyzer (DLS, Zeta potential), ultraviolet-visible spectrophotometer (UV-Vis), fluorescence spectrometer, etc., and the results are shown in fig. 1.
As can be seen from figure 1, the size of the synthesized nano-drug Ce6/Cyt c @ ZIF-8/HA is about 110 nm (A); the size distribution of different nano-drug samples is concentrated, which shows that the synthesized sample is more uniform (B); and can be seen through Zeta potential diagram (C) and ultraviolet visible light absorption spectrogram (D), protein drug Cyt C and photosensitizer Ce6 are successfully encapsulated in the metal organic framework; as can be seen from fluorescence spectrograms (E) and (F), when the encapsulated photosensitizer and the protein drug labeled by fluorescence are available, a fluorescence peak of Ce6 at 660 nm and a fluorescence peak of FITC at 520 nm are respectively shown in the spectral line of the nano drug Ce6/Cyt c @ ZIF-8/HA, and further, the successful encapsulation of the photosensitizer and the protein in a metal organic framework is proved.
2. The ability of the nano-drug sample synthesized in example 1 to generate active oxygen under 670 nm laser irradiation was examined, i.e., 1, 3-Diphenylisobenzofuran (DPBF) was used as an active oxygen indicator probe, after different nano-drug samples were mixed with DPBF, laser irradiation was performed for different times, the change in absorbance within the range of 300-600 nm was tested, and the absorbance at 415 nm was taken for normalization treatment to prove the active oxygen generating ability of the metal-organic framework nano-drug, the results are shown in fig. 2.
As can be seen from fig. 2, the absorption value of the nano-drug sample loaded with Ce6 at 415 nm decreases with the increase of the illumination time, while the sample not loaded with Ce6 has no obvious change, which indicates that the nano-drug loaded with Ce6 can generate active oxygen under the illumination condition.
3. The ability of the nano-drug synthesized in example 1 to respond to release was examined by dissolving the nano-drug in PBS buffer solution of pH =5.0 and pH =7.4, respectively, and measuring the absorption, and the results were shown in fig. 3, in which the nano-drug released Ce6 and Cyt c.
As can be seen from fig. 3, in PBS buffer with pH =5.0, the nano-drug Ce6/Cyt c @ ZIF-8/HA was significantly degraded, almost completely releasing the entrapped Ce6 and Cyt c, demonstrating its acid-responsive release capability.
4. The ability of the nano-drug synthesized in example 1 to catalyze hydrogen peroxide to generate oxygen and to improve the photodynamic action was examined by reacting the nano-drug with 500 μ M hydrogen peroxide and measuring the change in dissolved oxygen by an oxygen electrode. Meanwhile, DPBF is used as a probe, and the capacity of the nano-drug for generating active oxygen is illuminated in the presence of hydrogen peroxide under the conditions of normal oxygen and anaerobic reaction. The results are shown in FIG. 4.
As can be seen from FIG. 4, Cyt c existing in the nano-drug can effectively catalyze the decomposition of hydrogen peroxide into oxygen (A) and improve the active oxygen generating capacity (B), thereby being beneficial to improving the photodynamic therapy effect.
Example 3:
1. by taking a cervical cancer HeLa cell as a model, the ability of the nano-drug Ce6/Cyt c @ ZIF-8/HA to carry Ce6 and Cyt c at the cell level and the tumor cell targeting ability of HA are tested by using a confocal fluorescence microscope. Specifically, after incubating the nano-drug with L929 cells (mouse fibroblasts), HeLa cells and HA-blocked HeLa cells for 2 hours, fluorescence of Ce6 and FITC-Cyt c was detected by confocal fluorescence microscopy, and the results are shown in fig. 5.
As can be seen in FIG. 5, fluorescence images of Ce6 and FITC appear in HeLa cells, demonstrating that the nano-drug can successfully deliver Ce6 and Cyt c into cells.
2. The ability of different nano-drugs to generate active oxygen in cells was investigated in combination with the active oxygen fluorescence indicator 2',7' -dichlorofluorescence yellow diacetate (DCFH-DA). The method specifically comprises the steps of incubating nano-drugs with HeLa cells for 4 hours respectively, washing off the nano-drugs, adding a fluorescence indicator DCFH-DA, incubating for 20 minutes, dividing the incubation into two groups, wherein one group is used for irradiating the cells for 5 minutes at 670 nm, the other group is not used for irradiation for comparison, and the results are shown in figure 6 after irradiation by using a fluorescence microscope.
As can be seen from FIG. 6, the nano-drug group containing Ce6 (Ce6@ ZIF-8/HA, Ce6/Cyt c @ ZIF-8/HA, HA + Ce6/Cyt c @ ZIF-8/HA) shows obvious fluorescence of DCFH, which proves that the nano-drug containing Ce6 can generate active oxygen under illumination, so that the nano-drug can be used for cell photodynamic therapy.
3. The therapeutic effect of different nano-drugs under the condition of illumination and no illumination is investigated by combining a dead cell fluorescence indicator (propidium iodide, PI). The specific steps are that nano-drugs and HeLa cells are incubated for 4 hours respectively, then the nano-drugs are washed off, then the nano-drugs are divided into two groups respectively, wherein one group is used for irradiating the cells for 5 minutes under the condition of 670 nm, the other group is used for comparison without irradiation, after 24 hours, the cells are dyed with PI dye for 20 minutes, and then the detection is carried out by a fluorescence microscope, and the result is shown in figure 7.
As can be seen from fig. 7, in the absence of light, the killing effect of each nano-drug on cells is low; after illumination, compared with a test group (Control and Cyt c) without Ce6, the nano-drug group (Ce6@ ZIF-8/HA, Ce6/Cyt c @ ZIF-8/HA, HA + Ce6/Cyt c @ ZIF-8/HA) containing Ce6 HAs obviously improved killing capacity on cancer cells, and the result shows that the nano-drug group HAs a good photodynamic treatment effect. In addition, Ce6/Cyt c @ ZIF-8/HA is also improved to a certain extent compared with HA + Ce6/Cyt c @ ZIF-8/HA, because the effective uptake of the nano-drug by cells is reduced after HA blocking treatment, thereby reducing the effect of combined treatment.
4. The cell viability quantitative detection kit (CCK-8 kit) is used for quantitatively testing the treatment effect of the nano-drug under the conditions of illumination and no illumination. Specifically, HeLa cells are cultured in a 96-well plate, different nano-drugs are respectively added for incubation for 4 hours, the nano-drugs are washed off, then the cells are divided into two groups, wherein one group is subjected to 670 nm illumination for 5min, the other group is not subjected to illumination for comparison, after 24 hours, the detection is carried out according to the operation method of the cell viability quantitative detection kit, and the result is shown in figure 8.
As can be seen from fig. 8, in the absence of light, the killing effect of each nano-drug on cells is low; after illumination, compared with a nano-drug group (Ce6@ ZIF-8/HA, Ce6/Cyt c @ ZIF-8/HA, HA + Ce6/Cyt c @ ZIF-8/HA) without Ce6 group (Control and Cyt c), the killing capacity of the nano-drug group (Ce 6) to cancer cells is remarkably improved. In addition, Ce6/Cyt c @ ZIF-8/HA is also improved to a certain extent compared with HA + Ce6/Cyt c @ ZIF-8/HA, because the effective uptake of the nano-drug by cells is reduced after HA blocking treatment, thereby reducing the effect of combined treatment.
5. The treatment effect of the nano-drug under the conditions of illumination and no illumination is quantitatively tested by flow cytometry by using an apoptosis kit (annexin V-FITC/PI). Specifically, HeLa cells are cultured in a 6-well plate, different nano-drugs are respectively added for incubation for 4 hours, the nano-drugs are washed off, then the cells are divided into two groups, wherein one group is subjected to 670 nm illumination for 5min, the other group is not subjected to illumination for comparison, after 24 hours, detection is carried out by flow cytometry according to an apoptosis kit (annexin V-FITC/PI) operation method, and the result is shown in figure 9.
As can be seen from fig. 9, in the absence of light, the killing effect of each nano-drug on cells is low; after illumination, compared with a nano-drug group (Ce6@ ZIF-8/HA, Ce6/Cyt c @ ZIF-8/HA, HA + Ce6/Cyt c @ ZIF-8/HA) without Ce6 group (Control and Cyt c), the killing capacity of the nano-drug group (Ce 6) to cancer cells is remarkably improved. In addition, Ce6/Cyt c @ ZIF-8/HA is also improved to a certain extent compared with HA + Ce6/Cyt c @ ZIF-8/HA, because the effective uptake of the nano-drug by cells is reduced after HA blocking treatment, thereby reducing the effect of combined treatment.
The above description is only a preferred embodiment of the present invention, and all equivalent changes and modifications made in accordance with the claims of the present invention should be covered by the present invention.

Claims (9)

1. A tumor targeting nano-drug simultaneously encapsulating a photosensitizer and a protein is characterized in that: the tumor targeting nano-drug is dimethyl imidazole and Zn2+The self-assembled metal organic framework material ZIF-8 is used as a carrier, and simultaneously, a hydrophobic photosensitizer and a protein drug are encapsulated and modified by a modifier to form the nano-particles.
2. The tumor-targeted nano-drug simultaneously encapsulating photosensitizer and protein according to claim 1, characterized in that: the hydrophobic photosensitizer is one or more of chlorin e6, curcumin, hypericin, protoporphyrin, tetraphenylporphyrin, zinc phthalocyanine and hypocrellin B.
3. The tumor-targeted nano-drug simultaneously encapsulating photosensitizer and protein according to claim 1, characterized in that: the protein medicine is cytochrome c, carboxypeptidase G2, interferon alpha-2B, ribonuclease, interleukin-10, PD-1 antibody and granzyme B.
4. The tumor-targeted nano-drug simultaneously encapsulating photosensitizer and protein according to claim 1, characterized in that: the modifier is one or more of hyaluronic acid, polyethyleneimine, dextran, chitosan, fucose, albumin, gelatin, liposome and polyvinylpyrrolidone.
5. The tumor-targeted nano-drug simultaneously encapsulating photosensitizer and protein according to claim 1, characterized in that: the particle size of the nano-particles is 20-400 nm.
6. A method for preparing the tumor targeting nano-drug according to claims 1 to 5, characterized in that: the method comprises the following specific steps:
1) uniformly mixing 2-methylimidazole, a Protein drug and a hydrophobic photosensitizer, stirring and dispersing for 5min, then quickly dropwise adding an aqueous solution containing zinc acetate or zinc nitrate, stirring for 5-60 min, centrifuging for 5-60 min at 4 ℃ at 8000-14800 r/min, collecting lower-layer precipitates, and centrifuging and washing for multiple times by using water to obtain a front nano drug PS/Protein @ ZIF-8 encapsulated by a metal organic framework;
2) and re-dispersing the obtained PS/Protein @ ZIF-8 in water, slowly dropwise adding a modifier solution under an ultrasonic condition, stirring for 2-6 h in a dark place, adding absolute ethyl alcohol with the total volume of 1/10 in a reaction system, centrifugally washing for 20-40 min at 8000-14800 r/min, and centrifugally washing for multiple times by water to obtain the targeted nano-drug PS/Protein @ ZIF-8/SA.
7. The preparation method of the tumor-targeted nano-drug according to claim 6, characterized in that: the weight ratio of the hydrophobic photosensitizer and the protein medicine used in the step 1) to the zinc acetate or the zinc nitrate is 1-20: 1-20: 100, respectively; the molar ratio of the zinc acetate or the zinc nitrate to the 2-methylimidazole is 1: 1 to 200.
8. The preparation method of the tumor-targeted nano-drug according to claim 6, characterized in that: step 2) the mass ratio of PS/Protein @ ZIF-8 to the modifier in the reaction system is 1: 0.1 to 10.
9. The application of the tumor-targeted nano-drug as claimed in claim 1 in preparing an anti-tumor drug, which is characterized in that: the tumor targeted nano-drug has the characteristics of active targeting of tumor cells and drug release in response to tumor microenvironment, and can realize the cooperative treatment of photodynamic therapy and protein therapy while performing fluorescence imaging.
CN202010653123.0A 2020-07-08 2020-07-08 Tumor-targeted nano-drug simultaneously encapsulating photosensitizer and protein and application thereof Active CN111643673B (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
CN202010653123.0A CN111643673B (en) 2020-07-08 2020-07-08 Tumor-targeted nano-drug simultaneously encapsulating photosensitizer and protein and application thereof
PCT/CN2020/112583 WO2022007153A1 (en) 2020-07-08 2020-08-31 Tumor-targeting nanodrug simultaneously enclosing photosensitizer and protein, and use thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202010653123.0A CN111643673B (en) 2020-07-08 2020-07-08 Tumor-targeted nano-drug simultaneously encapsulating photosensitizer and protein and application thereof

Publications (2)

Publication Number Publication Date
CN111643673A true CN111643673A (en) 2020-09-11
CN111643673B CN111643673B (en) 2022-09-13

Family

ID=72342028

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202010653123.0A Active CN111643673B (en) 2020-07-08 2020-07-08 Tumor-targeted nano-drug simultaneously encapsulating photosensitizer and protein and application thereof

Country Status (2)

Country Link
CN (1) CN111643673B (en)
WO (1) WO2022007153A1 (en)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113018455A (en) * 2021-03-16 2021-06-25 北京电子科技职业学院 Hyaluronic acid modified nano carrier loaded with hydrophobic drugs as well as preparation method and application thereof
CN113372904A (en) * 2021-06-08 2021-09-10 青岛科技大学 Glutathione response nanoprobe for tumor imaging and targeted cooperative therapy and construction method thereof
CN113384696A (en) * 2021-06-07 2021-09-14 深圳大学 Nano photosensitizer, preparation method and application thereof
CN113384709A (en) * 2021-06-28 2021-09-14 西南大学 Preparation and application of glucan-protoporphyrin prodrug nano-micelle
CN113651872A (en) * 2021-08-09 2021-11-16 大连理工大学 Self-assembly nano photosensitizer based on amphiphilic polypeptide and preparation method and application thereof
CN113952470A (en) * 2021-08-31 2022-01-21 中国科学院长春应用化学研究所 Nanoparticles of dual active oxygen generator and preparation method and application thereof
CN114099706A (en) * 2021-11-30 2022-03-01 江南大学 MOF drug carrier for treating breast cancer and preparation method thereof
CN114129738A (en) * 2021-11-30 2022-03-04 广东省人民医院 Immunotherapy antibody composite material responding to tumor microenvironment and use for preparing antitumor drug
CN114657098A (en) * 2022-03-28 2022-06-24 深圳大学 A modified microorganism, modification method and application thereof, antitumor drug
CN114668712A (en) * 2022-03-24 2022-06-28 深圳大学 A kind of sustained-release microneedle patch and preparation method thereof
CN114848813A (en) * 2022-04-18 2022-08-05 湖北工业大学 A self-supplying H2O2/O2 and GSH-consuming metal-organic framework-coated nanoparticle and its preparation method and application
CN115887490A (en) * 2022-12-02 2023-04-04 中国科学院精密测量科学与技术创新研究院 A kind of acidic and glutathione-responsive manganese-based nanomaterial and its preparation method and application
CN116350798A (en) * 2023-03-08 2023-06-30 南京邮电大学 A composite nanomaterial capable of activating calcium overload and tumor cell pyroptosis and its preparation method and application
CN119409770A (en) * 2025-01-07 2025-02-11 天津医科大学 A high-efficiency polypeptide photosensitizer and its preparation method and application
CN119431497A (en) * 2023-07-31 2025-02-14 北京大学 Photosensitizer chimera targeting PD-L1 protein and preparation method and application thereof
CN119499373A (en) * 2024-10-22 2025-02-25 郑州大学 Preparation method and application of a cholesterol-consuming nanoreactor
CN119931074A (en) * 2025-01-21 2025-05-06 徐州医科大学 A nano metal organic framework compound and its preparation method and application

Families Citing this family (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN118252946A (en) * 2022-01-21 2024-06-28 同济大学 Application of polyclonal antibody Anti-DR5 Ab in promoting the specific binding of bacterial drug delivery system to tumor cells and improving the ability of bacterial drug delivery system to inhibit tumor cell growth
CN114601925B (en) * 2022-01-27 2023-10-17 西安交通大学医学院第一附属医院 Photosensitive nanomaterials co-modified with hyaluronic acid and RSL3, preparation methods and applications
CN114887077A (en) * 2022-02-15 2022-08-12 浙江大学 Preparation method of organic metal nano material with mitochondrion targeting capability
CN114437183A (en) * 2022-02-17 2022-05-06 中国农业科学院兰州兽医研究所 Method for improving thermal stability of virus-like particles based on metal organic framework biomimetic mineralization
CN114699537B (en) * 2022-03-07 2024-06-21 西安交通大学医学院第一附属医院 A ROS-responsive anticancer drug that improves the efficacy of hypoxia-sensitized PD-1 antibodies
CN114796156B (en) * 2022-04-18 2023-11-21 河北医科大学 A mitochondria-targeted photothermal/chemotherapy synergistic nanodrug delivery particle and its preparation method and application
CN115025238B (en) * 2022-05-19 2024-03-19 北京柏欧利诺生物科技有限公司 Size-controllable mitochondrion targeting photosensitive nanoparticle and preparation method thereof
CN115227828B (en) * 2022-06-23 2024-02-27 中国药科大学 Preparation method and application of magnetic targeting protein delivery nano assembly based on ferroferric oxide
CN114984303B (en) * 2022-07-01 2023-08-29 西南交通大学 A spray-type hydrogel dressing that can generate oxygen in situ, its preparation method and application
CN116004591B (en) * 2022-07-13 2024-04-05 吉林大学 A near-infrared driven thermophilic enzyme catalyzed anti-tumor targeted nanoparticle preparation
CN115531536B (en) * 2022-08-16 2023-09-22 南京师范大学 Preparation method and application of near-infrared BODIPY@ZIF-8 nanometer photosensitizer with high singlet oxygen efficiency
CN115137845B (en) * 2022-08-30 2022-11-01 潍坊医学院附属医院 A kind of metal-organic framework containing dynamic imine bond covalently simultaneously immobilizing doxorubicin and porphyrin complex and its preparation method and application
CN115385861B (en) * 2022-08-30 2024-03-29 内蒙古大学 Fluorescent probe and preparation method and application thereof
CN115737831A (en) * 2022-10-18 2023-03-07 南京医科大学康达学院 Nano-carrier for active targeting drug delivery of tumor, preparation method and application thereof
CN115737932B (en) * 2022-11-23 2024-04-26 国纳之星(上海)纳米科技发展有限公司 Preparation, product and application of bone cement loaded with X-ray induced photodynamic therapy/radiotherapy cooperative diagnosis and treatment integrated probe
CN116271084A (en) * 2023-01-04 2023-06-23 深圳市第二人民医院 Drug magnetic delivery system based on magnetotactic bacteria, and preparation method and application thereof
CN116077657A (en) * 2023-02-28 2023-05-09 中国科学院长春应用化学研究所 A kind of active oxygen nanometer material and preparation method thereof for regulating tumor microenvironment
CN116650706A (en) * 2023-04-27 2023-08-29 南昌大学 Nanometer dressing capable of forming gel in situ, preparation method, application and drug delivery device thereof
CN116903875B (en) * 2023-07-20 2025-05-30 合肥工业大学 A biosensor based on metal organic framework and its preparation method
CN118178352A (en) * 2024-04-10 2024-06-14 广东云曌医疗科技有限公司 Antibacterial drug nano material and preparation method and application thereof
CN119375204B (en) * 2024-10-25 2025-10-24 暨南大学 A surface-enhanced Raman probe based on ZIF-8 coated surface plasmon tungsten oxide and its preparation method and application
CN119529271B (en) * 2024-11-25 2025-12-05 湖北理工学院 A photosensitizer carrier, its preparation method and application
CN119529273A (en) * 2024-11-25 2025-02-28 湖北理工学院 A targeted nano photosensitizer carrier and its preparation method and application
CN119971032B (en) * 2024-12-29 2025-11-14 浙江工业大学 A type of HYP@GOx@Fe3O4@Lf nanoparticles and their preparation and application

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20120090317A (en) * 2011-02-07 2012-08-17 고려대학교 산학협력단 Particle killing microorganism by light and method killing microorganism by light
CN110200943A (en) * 2019-07-05 2019-09-06 北京化工大学 A kind of polyaminoacid coordination nanoparticle and preparation method thereof and application as the drug in sound power oncotherapy
CN110731961A (en) * 2014-10-14 2020-01-31 芝加哥大学 Metal organic framework, pharmaceutical preparation and use thereof in preparing medicament
CN110898223A (en) * 2019-12-13 2020-03-24 江南大学 Liver targeting therapeutic drug based on glycosyl metal framework material and preparation method thereof
CN111265533A (en) * 2019-11-25 2020-06-12 上海纳米技术及应用国家工程研究中心有限公司 Preparation method of core-shell nanoparticles based on lipid membrane and metal organic framework

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106362146B (en) * 2016-08-10 2019-04-05 福州大学 A kind of preparation and its application of ZIF-8@Phthalocyanine Zinc composite material
CN109529036A (en) * 2018-12-21 2019-03-29 上海纳米技术及应用国家工程研究中心有限公司 The preparation method of pH sensitivity and photo-thermal therapy probe based on metal organic frame ZIF-8
CN110522910B (en) * 2019-08-01 2020-11-06 山东大学 Nano-drug delivery system based on metal-organic framework and its preparation method and application
CN110693883A (en) * 2019-11-21 2020-01-17 安徽医科大学第一附属医院 Preparation method and application of zinc-organic framework drug-carrying system encapsulating rapamycin
CN111320760B (en) * 2020-02-28 2022-11-25 南开大学 Porous framework material, enzyme preparation containing porous framework material, preparation method and application

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20120090317A (en) * 2011-02-07 2012-08-17 고려대학교 산학협력단 Particle killing microorganism by light and method killing microorganism by light
CN110731961A (en) * 2014-10-14 2020-01-31 芝加哥大学 Metal organic framework, pharmaceutical preparation and use thereof in preparing medicament
CN110200943A (en) * 2019-07-05 2019-09-06 北京化工大学 A kind of polyaminoacid coordination nanoparticle and preparation method thereof and application as the drug in sound power oncotherapy
CN111265533A (en) * 2019-11-25 2020-06-12 上海纳米技术及应用国家工程研究中心有限公司 Preparation method of core-shell nanoparticles based on lipid membrane and metal organic framework
CN110898223A (en) * 2019-12-13 2020-03-24 江南大学 Liver targeting therapeutic drug based on glycosyl metal framework material and preparation method thereof

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ERIK SEDLAK，ET AL.: "Inner mechanism of protection of mitochondrial electron-transfer proteins against oxidative damage. Focus on hydrogen peroxide decomposition", 《BIOCHIMIE》 *
HONG CHENG，ET AL.: "An O2 Self-Sufficient Biomimetic Nanoplatform for Highly Specific and Efficient Photodynamic Therapy", 《 ADVANCED FUNCTIONAL MATERIALS》 *
XINWEI FU，ET AL.: "A natural polysaccharide mediated MOF-based Ce6 delivery system with improved biological properties for photodynamic therapy", 《JOURNAL OF MATERIALS CHEMISTRY B》 *

Cited By (24)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113018455A (en) * 2021-03-16 2021-06-25 北京电子科技职业学院 Hyaluronic acid modified nano carrier loaded with hydrophobic drugs as well as preparation method and application thereof
CN113384696A (en) * 2021-06-07 2021-09-14 深圳大学 Nano photosensitizer, preparation method and application thereof
CN113372904A (en) * 2021-06-08 2021-09-10 青岛科技大学 Glutathione response nanoprobe for tumor imaging and targeted cooperative therapy and construction method thereof
CN113384709B (en) * 2021-06-28 2022-03-11 西南大学 Preparation and application of a dextran-protoporphyrin prodrug nanomicelle
CN113384709A (en) * 2021-06-28 2021-09-14 西南大学 Preparation and application of glucan-protoporphyrin prodrug nano-micelle
CN113651872A (en) * 2021-08-09 2021-11-16 大连理工大学 Self-assembly nano photosensitizer based on amphiphilic polypeptide and preparation method and application thereof
CN113952470A (en) * 2021-08-31 2022-01-21 中国科学院长春应用化学研究所 Nanoparticles of dual active oxygen generator and preparation method and application thereof
CN113952470B (en) * 2021-08-31 2023-08-29 中国科学院长春应用化学研究所 Nanoparticles of a dual active oxygen generator and its preparation method and application
CN114099706A (en) * 2021-11-30 2022-03-01 江南大学 MOF drug carrier for treating breast cancer and preparation method thereof
CN114129738A (en) * 2021-11-30 2022-03-04 广东省人民医院 Immunotherapy antibody composite material responding to tumor microenvironment and use for preparing antitumor drug
CN114099706B (en) * 2021-11-30 2024-10-01 江南大学 A MOF drug carrier for breast cancer treatment and preparation method thereof
CN114668712A (en) * 2022-03-24 2022-06-28 深圳大学 A kind of sustained-release microneedle patch and preparation method thereof
CN114668712B (en) * 2022-03-24 2023-09-26 深圳大学 Sustained-release microneedle patch and preparation method thereof
CN114657098A (en) * 2022-03-28 2022-06-24 深圳大学 A modified microorganism, modification method and application thereof, antitumor drug
CN114848813A (en) * 2022-04-18 2022-08-05 湖北工业大学 A self-supplying H2O2/O2 and GSH-consuming metal-organic framework-coated nanoparticle and its preparation method and application
CN115887490A (en) * 2022-12-02 2023-04-04 中国科学院精密测量科学与技术创新研究院 A kind of acidic and glutathione-responsive manganese-based nanomaterial and its preparation method and application
CN115887490B (en) * 2022-12-02 2025-04-15 中国科学院精密测量科学与技术创新研究院 Acidic and glutathione responsive manganese-based nanomaterial and preparation method and application thereof
CN116350798A (en) * 2023-03-08 2023-06-30 南京邮电大学 A composite nanomaterial capable of activating calcium overload and tumor cell pyroptosis and its preparation method and application
CN119431497A (en) * 2023-07-31 2025-02-14 北京大学 Photosensitizer chimera targeting PD-L1 protein and preparation method and application thereof
CN119499373A (en) * 2024-10-22 2025-02-25 郑州大学 Preparation method and application of a cholesterol-consuming nanoreactor
CN119499373B (en) * 2024-10-22 2025-10-10 郑州大学 Preparation method and application of a cholesterol-consuming nanoreactor
CN119409770A (en) * 2025-01-07 2025-02-11 天津医科大学 A high-efficiency polypeptide photosensitizer and its preparation method and application
CN119409770B (en) * 2025-01-07 2025-04-25 天津医科大学 Efficient polypeptide photosensitizer and preparation method and application thereof
CN119931074A (en) * 2025-01-21 2025-05-06 徐州医科大学 A nano metal organic framework compound and its preparation method and application

Also Published As

Publication number Publication date
WO2022007153A1 (en) 2022-01-13
CN111643673B (en) 2022-09-13

Similar Documents

Publication Publication Date Title
CN111643673B (en) Tumor-targeted nano-drug simultaneously encapsulating photosensitizer and protein and application thereof
CN108653288B (en) Hypoxic response polymer nanoparticle and application thereof
Liang et al. A novel Pt–TiO2 heterostructure with oxygen‐deficient layer as bilaterally enhanced sonosensitizer for synergistic chemo‐sonodynamic cancer therapy
Xia et al. Glutathione responsive nitric oxide release for enhanced photodynamic therapy by a porphyrinic MOF nanosystem
Wang et al. Nanomaterials and singlet oxygen photosensitizers: potential applications in photodynamic therapy
Huang et al. Phthalocyanine-based coordination polymer nanoparticles for enhanced photodynamic therapy
Yang et al. Construction of pH/glutathione responsive chitosan nanoparticles by a self-assembly/self-crosslinking method for photodynamic therapy
Zhu et al. Facile preparation of indocyanine green and tiny gold nanoclusters co-loaded nanocapsules for targeted synergistic sono-/photo-therapy
Xia et al. Enhanced photodynamic therapy through supramolecular photosensitizers with an adamantyl-functionalized porphyrin and a cyclodextrin dimer
Jiao et al. Rational design of oxygen deficient TiO 2− x nanoparticles conjugated with chlorin e6 (Ce6) for photoacoustic imaging-guided photothermal/photodynamic dual therapy of cancer
Gong et al. Self-assembly of nanomicelles with rationally designed multifunctional building blocks for synergistic chemo-photodynamic therapy
Gomes et al. Photobiological and ultrastructural studies of nanoparticles of poly (lactic-co-glycolic acid)-containing bacteriochlorophyll-a as a photosensitizer useful for PDT treatment
CN116178448B (en) Porphyrin-based coordination molecular cage and its preparation method and application
Lin et al. A phthalocyanine-based liposomal nanophotosensitizer with highly efficient tumor-targeting and photodynamic activity
Zhang et al. Versatile gadolinium (III)-phthalocyaninate photoagent for MR/PA imaging-guided parallel photocavitation and photodynamic oxidation at single-laser irradiation
Liu et al. X-ray-triggered CO release based on GdW10/MnBr (CO) 5 nanomicelles for synergistic radiotherapy and gas therapy
CN105999283B (en) A kind of preparation method for the hectorite package gold nano grain that the polyethyleneimine-loading adriamycin is hyaluronic acid decorated
Xu et al. Anti-osteosarcoma trimodal synergistic therapy using NiFe-LDH and MXene nanocomposite for enhanced biocompatibility and efficacy
CN113751079B (en) Perovskite-titanium dioxide nano composite photocatalyst loaded by biological material and construction method and application thereof
Chen et al. Porphyrin-based covalent organic frameworks as doxorubicin delivery system for chemo-photodynamic synergistic therapy of tumors
Wu et al. Using host–guest interactions at the interface of quantum dots to load drug molecules for biocompatible, safe, and effective chemo-photodynamic therapy against cancer
Guo et al. Highly efficient tumor oxygen supplementation MnO2 nano-MOF encapsulated Sorafenib for multiple synergistic CDT/PDT/RT
Zheng et al. Aptamer-Modified Mesoporous Silica Nanoparticle for Nitric Oxide-Enhanced Targeted Sonodynamic Therapy against Lung Cancer
Wen et al. Bimetallic Au–Ag nanocages extended TPP conjugate structure for self-enhancing therapy of tumors
Sun et al. Pt/Ag‐PEG‐Ce6 nanosystem with enhanced near‐infrared absorption and peroxidase‐like activity for synergistic photodynamic/photothermal therapy

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