CN107802836B - Tumor targeted photo-thermal medicament, preparation method and application - Google Patents
Tumor targeted photo-thermal medicament, preparation method and application Download PDFInfo
- Publication number
- CN107802836B CN107802836B CN201711311833.XA CN201711311833A CN107802836B CN 107802836 B CN107802836 B CN 107802836B CN 201711311833 A CN201711311833 A CN 201711311833A CN 107802836 B CN107802836 B CN 107802836B
- Authority
- CN
- China
- Prior art keywords
- tumor
- medicament
- preparation
- photothermal
- mote
- 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.)
- Active
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Physics & Mathematics (AREA)
- Biomedical Technology (AREA)
- Nanotechnology (AREA)
- Optics & Photonics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a tumor targeted photo-thermal medicament, a preparation method and application thereof. The invention synthesizes the medicament with the photothermal antitumor effect by carrying out hydrophilic modification on molybdenum telluride through PEG with a targeting group modified by sulfydryl. The medicament has the characteristic of tumor cell targeting, and can realize the curative effect of inhibiting the proliferation of tumor cells through the photothermal effect.
Description
Technical Field
The invention belongs to the technical field of nano materials, and particularly relates to a tumor-targeted photo-thermal medicament, and a preparation method and application thereof.
Background
Photothermal therapy is an emerging therapeutic approach based on the generation of far infrared waves from light-activated materials. With the development of photothermal reagents such as conjugated organic groups, carbon nanotubes, gold nanorods, etc., photothermal therapy has been widely used for tumor imaging and treatment. The specificity and selectivity of photothermal agents plays a key role in diagnostic and therapeutic proceduresThe function of the bond. The geometrical structure of the nano material has great influence on the photo-thermal effect of the nano material. In recent years, MoS with nanometer-scale thickness2,MoSe2,WS2,WSe2Isotransition metal disulfides have attracted considerable attention. Due to the unique physical and chemical properties, the transition metal dichalcogenide has strong application potential in electronic components and parts, photocatalysis and energy storage. Inspired by electrochemical applications, more and more researchers are working on the applications of transition metal dichalcogenides with excellent optical and electronic properties for cancer imaging and therapy. For example, Liu [ 2 ] has been studied in a recent study of a combination therapy of photothermal and chemotherapyAdvanced materials2014, 26, 3433.]With his colleagues prepared a MoS2And (4) nano flakes.
Molybdenum ditelluride is a gray hexagonal powdery solid. Can be decomposed in alkali, is insoluble in water, is soluble in nitric acid and is stable in air. Can be used as a novel semiconductor material instead of silicon. At present, MoTe is not seen2Can be used for multifunctional therapy of cancer.
Disclosure of Invention
The invention solves the first technical problem by providing a preparation method of a tumor-targeted photothermal medicament. The method uses molybdenum ditelluride for multifunctional therapy of cancer, and prepares MoTe by mechanical ball milling method2The nano-flake is functionalized by thiol reaction, so that the tumor targeting property and biocompatibility are endowed. The invention provides MoTe with excellent biocompatibility2Nanoflakes exhibit strong near-infrared absorption, low toxicity and in vivo degradability properties, making them a promising agent for photothermal therapy.
The second technical problem to be solved by the invention is to provide the application of the tumor-targeted photothermal medicine prepared by the method.
In order to solve the first technical problem, the invention provides a preparation method of a tumor-targeted photothermal medicament, which comprises the following steps:
a) ball-milling the molybdenum telluride crystal in a high-speed ball mill for 24-36 h at the rotation speed of 200-800 rpm, uniformly dispersing the ball-milled powder in deionized water in an ice bath by using a sound wave degradation method,
b) mixing and stirring molybdenum telluride dispersed in water and sulfhydryl modified PEG with targeting groups according to the mass ratio of 1:1 for reaction for 48 h, and then centrifugally separating at 8000 rpm to obtain MoTe with excellent biocompatibility2And (4) nano flakes.
The sound wave degradation method comprises the following steps: 0-10oAnd C, stripping the ball-milled powder under the action of a cell crusher, wherein the crushing time is 6-12 h, and the obtained nano-sheet layer is 1-10 molecular layers.
Preferably, in step b), the targeting group is RGD, cRGD, HA, PAA.
Preferably, in step b), the molecular weight of PEG may be 200-.
Further, the invention provides the tumor-targeted photothermal agent prepared by the method.
In order to solve the second technical problem, the invention provides an application of the tumor-targeted photothermal agent in preparing an anti-tumor drug.
The starting materials of the present invention are commercially available, unless otherwise specified, and the equipment used in the present invention may be any equipment conventionally used in the art or may be any equipment known in the art.
Compared with the prior art, the invention has the following beneficial effects:
the invention selects the molybdenum telluride nano material with high photothermal conversion rate as the photothermal reagent, avoids the use of heavy metal and high-toxicity aromatic compounds, and has low cost and fast in vivo metabolism compared with similar products in the market. The novel tumor-targeted photo-thermal medicament has strong absorption on near infrared light; has good inhibition effect on the growth of tumor cells and higher lethality on the tumor cells; the photo-thermal conversion efficiency is high; can induce apoptosis.
Drawings
FIG. 1: TEM images of molybdenum telluride photothermal antitumor agents.
FIG. 2: absorption of ultraviolet light by the antitumor agent.
FIG. 3: a. experiment of inhibiting growth of mouse breast cancer cell by using the anti-tumor photothermal agent. b. Experiment on growth inhibition of mouse breast cancer cells by the anti-tumor photothermal medicament after being irradiated by far infrared rays.
FIG. 4: the temperature distribution of the anti-tumor photo-thermal medicament under far infrared irradiation to the temperature of a water system.
FIG. 5: the influence of the far infrared radiation anti-tumor photo-thermal medicament on the system temperature changes along with the time and the influence of water on the system temperature is compared.
FIG. 6: analysis of apoptosis of cancer cells under different conditions of action.
Detailed Description
The features and advantages of the present invention will be further understood from the following detailed description taken in conjunction with the accompanying drawings. The examples provided are merely illustrative of the method of the present invention and do not limit the remainder of the disclosure in any way.
Example 1 synthesis of tumor-targeting photothermal agent 1:
(1) and ball-milling the molybdenum telluride crystals in a high-speed ball mill for 48 hours at the rotating speed of 400 rmp.
(2) Uniformly dispersing the ball-milled powder in deionized water by using a cell crusher, wherein the crushing time is 12 hours, and the temperature is 0-4 DEGoC。
(3) Mixing molybdenum telluride dispersed in water with HS-PEG-cRGD (Mn = 25.7 kg/mol) according to the mass ratio of 1:1, stirring and reacting for 48 h, and then centrifuging at 8000 rpm to obtain MoTe with excellent biocompatibility2And (4) nano flakes.
(4) The material structure was characterized by a projection electron microscope (fig. 1) and the obtained product was stored at-18 ℃ protected from light.
[ example 2 ] ultraviolet-visible absorption spectrum of tumor-targeted photothermal agent 1
MoTe2The UV-visible absorption spectrum of the aqueous nanoflake solution was measured by a UV-Vis spectrophotometer (Thermoscientific, Waltham, Mass.). The results are shown in FIG. 2, MoTe2The nanoplatelets absorb light in the ultraviolet and visible rangeThe spectrum shows strong near infrared absorption at 800-950 nm, thus proving MoTe2The nano-flake is a compound with photo-thermal conversion potential, and the optimal absorption wavelength range is 800-950 nm.
[ example 3 ] tumor-targeting photothermal agent 1 acting on mouse breast cancer cells
Mouse breast cancer cells were seeded in 2 96-well plates at a density of 6000 cells/well, and cultured with 0.1 ml of a medium for 24 hours. Then, the culture medium is prepared into MoTe with different concentrations2Nanoflake PBS solution was added to each well separately. The culture was maintained at 37 ℃ for 48 hours in the absence of light. The dark toxicity group was cultured for 24 hours under dark conditions. To evaluate the phototoxicity of the material, the material that has not been endocytosed was replaced with fresh medium after 6 hours of incubation and then irradiated with NIR laser. 808 nm near infrared light is used for each hole, and the power is 1W cm-1Laser irradiation of (2) for 1 minute. The culture was continued for 24 hours. Then, 20. mu.l of MTT (dissolved in 5 mg/ml PBS buffer) was added to each well. After a total incubation time of 4 hours, the medium was aspirated and 150. mu.l of dimethyl sulfoxide was added. And (3) measuring the light absorption value at 570 nm in each hole by using a microplate reader, and calculating the cell survival rate to further obtain the phototoxicity and dark toxicity of the material obtained in the example 1 to the mouse breast cancer cells.
The results are shown in fig. 3, the material after illumination has great toxicity to mouse breast cancer cells, thereby proving that the photothermal anti-tumor compound has the characteristic of selectively killing tumor cells.
Example 4 testing of photo-thermal Properties of hydrophilic molybdenum telluride nanoflakes
In order to test the photo-thermal performance of the hydrophilic molybdenum telluride nanoflakes, the hydrophilic nanoflakes and the blank control were irradiated with 808 nm far infrared laser. The course of laser irradiation was recorded with an infrared thermal imager.
As a result, as shown in fig. 4 and 5, the temperature of the molybdenum telluride flake group was significantly increased with the increase of the irradiation time, and the blank group had almost no temperature change.
[ example 5 ] tumor-targeting photothermal agent 1 induces apoptosis of tumor cells
Mouse breast cancer cells were treated with 1 × 105The cells were cultured in six-well plates at a density of one cell/well and in 2 ml of medium at 37 ℃. After 24 hours, medium with dissolved material and blank medium were added to the six-well plate. After further incubation for 6 hours, the cells were irradiated with a laser at 808 nm. In contrast to irradiation with laser light alone or addition of material alone without any treatment. After further incubation for 18 hours, all cells were trypsinized and harvested by centrifugation. After washing with PBS and annexin buffer, all cells were stained with FITC for 30 min and assayed by flow cytometry.
The results are shown in fig. 6, the material group after far infrared irradiation shows obvious apoptosis, which well verifies that the material has excellent photothermal effect.
Claims (5)
1. The preparation method of the tumor-targeted photothermal agent is characterized by comprising the following steps:
a)MoTe2preparing nano flakes: ball-milling the molybdenum telluride crystal in a high-speed ball mill for 24-36 h at a rotation speed of 200-800 rpm, then stripping the ball-milled powder under the action of a cell crusher to obtain a molecular layer composition with 1-10 nanosheets, uniformly dispersing the molecular layer composition in deionized water, wherein the crushing time is 6-12 h and the temperature is 0-10oC;
b) Preparing a tumor-targeted photothermal medicament: MoTe to be dispersed in Water2Mixing and stirring the nano-sheets and PEG modified by sulfydryl and having a targeting group according to the mass ratio of 1:1 for reaction for 48 hours, and then centrifugally separating at 8000 rpm to obtain MoTe with excellent biocompatibility2And (4) nano flakes.
2. The method of claim 1, wherein in step b), the targeting group is RGD, cRGD, HA, PAA.
3. The method as claimed in claim 1, wherein the molecular weight of PEG in step b) is 200-5000.
4. A tumor-targeted photothermal agent prepared by the method of claim 1.
5. The use of the tumor-targeted photothermal agent of claim 4 in the preparation of an antitumor drug.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201711311833.XA CN107802836B (en) | 2017-12-11 | 2017-12-11 | Tumor targeted photo-thermal medicament, preparation method and application |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201711311833.XA CN107802836B (en) | 2017-12-11 | 2017-12-11 | Tumor targeted photo-thermal medicament, preparation method and application |
Publications (2)
Publication Number | Publication Date |
---|---|
CN107802836A CN107802836A (en) | 2018-03-16 |
CN107802836B true CN107802836B (en) | 2020-09-08 |
Family
ID=61589896
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201711311833.XA Active CN107802836B (en) | 2017-12-11 | 2017-12-11 | Tumor targeted photo-thermal medicament, preparation method and application |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN107802836B (en) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113265763B (en) * | 2021-05-12 | 2022-12-13 | 广西医科大学 | Near-infrared light response electrostatic spinning PCL/MoS 2 Nanofiber membrane and preparation method thereof |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103705928A (en) * | 2013-12-27 | 2014-04-09 | 中国科学院高能物理研究所 | Single-layer MoS2 nano-chip, preparation method and nano-drug carrier |
CN103896222A (en) * | 2012-12-24 | 2014-07-02 | 中国科学技术大学 | Ultrathin nanosheet semiconductor material and preparation method and application thereof |
CN106188590A (en) * | 2016-07-14 | 2016-12-07 | 复旦大学 | Polymer hybrid PEM that metallo-organic framework is modified and preparation method thereof |
CN106512002A (en) * | 2016-10-21 | 2017-03-22 | 天津大学 | Multifunctional nano hybrid integrating CT imaging and phototherapy and preparation method thereof |
CN106563130A (en) * | 2016-10-31 | 2017-04-19 | 深圳先进技术研究院 | Stripping preparation method of molybdenum disulfide nanosheet and applications of molybdenum disulfide nanosheet |
WO2017194955A1 (en) * | 2016-05-13 | 2017-11-16 | Nanoco Technologies Ltd | Chemical vapor deposition method for fabricating two-dimensional materials |
CN107375928A (en) * | 2017-07-28 | 2017-11-24 | 北京化工大学 | A kind of preparation method and application of cancer target photo-thermal therapy nano-carrier |
-
2017
- 2017-12-11 CN CN201711311833.XA patent/CN107802836B/en active Active
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103896222A (en) * | 2012-12-24 | 2014-07-02 | 中国科学技术大学 | Ultrathin nanosheet semiconductor material and preparation method and application thereof |
CN103705928A (en) * | 2013-12-27 | 2014-04-09 | 中国科学院高能物理研究所 | Single-layer MoS2 nano-chip, preparation method and nano-drug carrier |
WO2017194955A1 (en) * | 2016-05-13 | 2017-11-16 | Nanoco Technologies Ltd | Chemical vapor deposition method for fabricating two-dimensional materials |
CN106188590A (en) * | 2016-07-14 | 2016-12-07 | 复旦大学 | Polymer hybrid PEM that metallo-organic framework is modified and preparation method thereof |
CN106512002A (en) * | 2016-10-21 | 2017-03-22 | 天津大学 | Multifunctional nano hybrid integrating CT imaging and phototherapy and preparation method thereof |
CN106563130A (en) * | 2016-10-31 | 2017-04-19 | 深圳先进技术研究院 | Stripping preparation method of molybdenum disulfide nanosheet and applications of molybdenum disulfide nanosheet |
CN107375928A (en) * | 2017-07-28 | 2017-11-24 | 北京化工大学 | A kind of preparation method and application of cancer target photo-thermal therapy nano-carrier |
Non-Patent Citations (7)
Title |
---|
Drug Delivery with PEGylated MoS 2 Nano-sheets for Combined Photothermal and Chemotherapy of Cancer;Teng Liu et al;《Advanced. Materials》;20140220;3433页左栏第2段、右栏第2段,3435页右栏第3段、第5段,3438页左栏第2段,supporting information第2页第1段 * |
Facile synthesis of biocompatible MoSe2 nanoparticles for efficient targeted photothermal therapy of human lung cancer;Chunlei Zhong et al;《RSC Advances》;20170123;7382–7391 * |
Graphene-Like Two-Dimensional Materials;Mingsheng Xu et al;《CHEMICAL REVIEWS》;20130103;3766-3798 * |
NIR Light-Triggered Degradable MoTe2 Nanosheets for Combined Photothermal and Chemotherapy of Cancer;Ning Ma et al;《Advanced Functional Materials》;20180622;1-11 * |
Polydopamine Coated Selenide Molybdenum: A New Photothermal Nanocarrier for Highly Effective Chemo-Photothermal Synergistic Therapy;Chao Wang et al;《ACS Biomaterials Science & Engineering》;20160916;2011-2017 * |
Size effect on near infrared photothermal conversion properties of liquid-exfoliated MoS2 and MoSe2;Yanbang Zhang et al;《Superlattices and Microstructures》;20161128;22-27 * |
二维过渡金属硫族化合物在生物医学中的应用;刘腾 等;《化学学报》;20150626;902-912 * |
Also Published As
Publication number | Publication date |
---|---|
CN107802836A (en) | 2018-03-16 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Kadian et al. | Recent advancements in synthesis and property control of graphene quantum dots for biomedical and optoelectronic applications | |
Tuerhong et al. | Review on carbon dots and their applications | |
Xiao et al. | A pH-responsive platform combining chemodynamic therapy with limotherapy for simultaneous bioimaging and synergistic cancer therapy | |
CN106267204B (en) | A kind of composite material and preparation method and application of black phosphorus nanometer sheet-antitumoral compounds | |
Liu et al. | Synthesis and optimization of MoS2@ Fe3O4‐ICG/Pt (IV) nanoflowers for MR/IR/PA bioimaging and combined PTT/PDT/chemotherapy triggered by 808 nm laser | |
Nair et al. | Rapid, acid-free synthesis of high-quality graphene quantum dots for aggregation induced sensing of metal ions and bioimaging | |
Wang et al. | In-vitro photothermal therapy using plant extract polyphenols functionalized graphene sheets for treatment of lung cancer | |
Dong et al. | Poly (ethylene glycol) conjugated nano-graphene oxide for photodynamic therapy | |
Sun et al. | In situ synthesis of graphene oxide/gold nanorods theranostic hybrids for efficient tumor computed tomography imaging and photothermal therapy | |
Wang et al. | 2D nanostructures beyond graphene: preparation, biocompatibility and biodegradation behaviors | |
Lu et al. | Molybdenum disulfide nanosheets: From exfoliation preparation to biosensing and cancer therapy applications | |
Bai et al. | Photosensitizer-conjugated Bi2Te3 nanosheets as theranostic agent for synergistic photothermal and photodynamic therapy | |
Shakibaie et al. | Cytotoxic and antioxidant activity of the biogenic bismuth nanoparticles produced by Delftia sp. SFG | |
Ghosh et al. | Nitrogen and sulphur doped carbon dot: An excellent biocompatible candidate for in-vitro cancer cell imaging and beyond | |
Tang et al. | Cu 2 ZnSnS 4 nanocrystals for microwave thermal and microwave dynamic combination tumor therapy | |
Rajasekar et al. | Chitosan coated molybdenum sulphide nanosheet incorporated with tantalum oxide nanomaterials for improving cancer photothermal therapy | |
CN102000350B (en) | Folic acid receptor targeting type nano gold particles and preparation method thereof | |
Liu et al. | Synthesis of functional hollow WS2 particles with large surface area for Near-Infrared (NIR) triggered drug delivery | |
Qing et al. | An activatable nanoenzyme reactor for coenhanced chemodynamic and starving therapy against tumor hypoxia and antioxidant defense system | |
Yang et al. | Mitochondrial targeting nano-curcumin for attenuation on PKM2 and FASN | |
Li et al. | A targeted agent with intercalation structure for cancer near-infrared imaging and photothermal therapy | |
CN107802836B (en) | Tumor targeted photo-thermal medicament, preparation method and application | |
Dar et al. | Photothermal therapy using graphene quantum dots | |
Lu et al. | A carrier-free nanoparticle with dual NIR/acid responsiveness by co-assembly of enediyne and IR820 for combined PTT/chemotherapy | |
Sang et al. | Black phosphorus nanosheets and paclitaxel encapsulated hydrogel for synergistic photothermal-chemotherapy |
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 |