CN104208725A - Activated carbon nanosphere and application thereof to tumor boundary and lymph gland tracing - Google Patents

Activated carbon nanosphere and application thereof to tumor boundary and lymph gland tracing Download PDF

Info

Publication number
CN104208725A
CN104208725A CN201410468300.2A CN201410468300A CN104208725A CN 104208725 A CN104208725 A CN 104208725A CN 201410468300 A CN201410468300 A CN 201410468300A CN 104208725 A CN104208725 A CN 104208725A
Authority
CN
China
Prior art keywords
microsphere
active carbon
composite nano
carbon composite
activated carbon
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN201410468300.2A
Other languages
Chinese (zh)
Inventor
崔大祥
高国
孙容瑾
邱培宇
张英鸽
王玉霞
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.)
Shanghai Jiaotong University
Original Assignee
Shanghai Jiaotong 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 Shanghai Jiaotong University filed Critical Shanghai Jiaotong University
Priority to CN201410468300.2A priority Critical patent/CN104208725A/en
Publication of CN104208725A publication Critical patent/CN104208725A/en
Pending legal-status Critical Current

Links

Landscapes

  • Medicinal Preparation (AREA)
  • Carbon And Carbon Compounds (AREA)

Abstract

The invention discloses an activated carbon nanosphere which is prepared by taking activated carbon particles with the particle sizes of 10-100nm as carriers, and the surfaces of the activated carbon particles are compounded with an organic dyestuff. The activated carbon nanosphere disclosed by the invention is rather strong in dyeing property, remarkable in tracing effect and capable of remarkably showing a lymph tracing effect for a tested living body within half a hour, realizing multi-mode imaging and directly observing the trace of the nanosphere from tumors, tissues or organs through naked eyes.

Description

Active carbon Nano microsphere and the application in tumor boundaries and Lymph nodes trace thereof
Technical field
The present invention relates to a kind of nano-particle, particularly relating to a kind of take active carbon as composite nanometer particle prepared by carrier, and the application in the determination of this nanoparticles tumor boundaries and lymphatic metastasis spike.
Background technology
Current China is every year because of nearly 3,000,000 examples of cancer mortality case, and surgical operation is still first-selection and the most effective Therapeutic Method.But survival rates rests on reduced levels both at home and abroad, and for gastric cancer, within postoperative 5 years, survival rate great majority are hovered 20 ~ 30% always.When a very large reason is exactly tumor resection, lymph node is removed thorough, and the tumor cell of infiltration, through lymph tube wall, with lymph fluid shifts along lymphatic vessel, to make after operation in patients recurrence in a short time or transfer and dead.
Chinese invention patent application 201110045024.5 discloses a kind of stomach lymph node and knows method, comprise and first cut hepatogastric ligament, clean the 12nd group of lymph node of hepatodudenal ligament, district's lymph node on the 5th group of pylorus is cleaned again by above pylorus, and cut off, the ligation stomach right side is dynamic, vein, again along diaphram foot, omentum minus internal film tissue cuts by caudate lobe of liver lower edge, along clockwise direction on the right side of cardia district, clean the 1st group of right lymph node of cardia and the 3rd group of lymph node of lesser curvature of stomach, capsula pancreatis is cut again along pancreas upper limb place, to pylorus, clean the 6th group of subpyloric lymph nodes, join with district on pylorus, do that surface is cleaned by the 7th group of left gastric artery, by the 8th group of common hepatic artery successively, the 9th group of coeliac artery is taken up the dry lymph node of splenic artery, thus completed the removing of lymph node again along common hepatic artery.This technology proposes the lymph node dissection method with " surrounding and annihilating formula " first, and takes more reasonably to remove approach, and simplify the operation step greatly, improves operability, reduces reset procedure to the damage of surrounding tissue, significantly reduces wound surface, improve the safety of operation.
Therefore, removing thoroughly the lymph node of tumor region, is tumor key at least, seems particularly important.As a rule, lymph node and lymphatic vessel are not easily gone out by discernable by eye.Utilizing some material to carry out spike to lymph, is very helpful for lymph cleaning.
Active carbon coloring is excellent, and good biocompatibility, has no side effect, and is desirable lymphatic tracer.There is two large problems and constrain its application on clinical medicine in common active carbon, one is that particle diameter is comparatively large, and two is hydrophobic properties.Therefore, active carbon is applied to tracer as carrier and still has larger technical difficulty.
Summary of the invention
One object of the present invention is to provide a kind of active carbon composite nano-microsphere, is carrier with activated carbon granule, Compound partition wall agent on it.
Another object of the present invention is the preparation method providing a kind of active carbon composite nano-microsphere, and technique is simple, and obtained microsphere can realize multi-modal imaging.
Another object of the present invention is to provide a kind of active carbon composite nano-microsphere, as tracer, for the confirmation of tumor boundaries.
Another object of the present invention is to provide a kind of active carbon composite nano-microsphere, as tracer, for lymphatic metastasis spike.
A kind of active carbon composite nano-microsphere provided by the invention, with particle diameter 10nm ~ 100nm activated carbon granule for carrier, at its surface recombination organic dyestuff.
A kind of active carbon composite nano-microsphere provided by the invention, with particle diameter 10nm ~ 100nm activated carbon granule for carrier, coated material is compound in activated carbon granule surface, and organic dyestuff is compound in coated material.
In the present invention, compound comprises: but be not limited only to chemical coupling, Electrostatic Absorption and embedding etc., and such as: organic dyestuff chemical coupling is in coated material.
The preparation method of a kind of active carbon composite nano-microsphere provided by the invention, its step is as follows:
First active carbon is positioned over grinding in ball grinder, is put in water and leaves standstill two days, get upper strata suspension after taking-up, obtain active carbon Nano microsphere, its particle diameter is at 10nm ~ 100nm;
Then, add activator, stir 20 minutes ~ 40 minutes, to activate further the carboxyl of activated carbon surface, and the activated carbon microballon of obtained surface active;
Then, add coated material, stir 6 hours ~ 10 hours, the obtained active carbon complex microsphere with water-wet behavior;
Finally, add organic dyestuff, with the obtained further compound of active carbon composite nano-microsphere with water-wet behavior, and obtained active carbon composite nano-microsphere.
The preparation method of active carbon composite nano-microsphere of the present invention, its active carbon Nano microsphere and activator are mol ratio 20:1 ~ 80:1, prioritizing selection 30:1 ~ 50:1, as: but be not limited only to 30:1,31:1,32:1,33:1,34:1,35:1,36:1,37:1,38:1,39:1,40:1,41:1,42:1,43:1,44:1,45:1,46:1,47:1,48:1,49:1 and 50:1.
The preparation method of active carbon composite nano-microsphere of the present invention, the active carbon Nano microsphere of its surface active and coated material are mass ratio 20:1 ~ 80:1, prioritizing selection 20:1 ~ 40:1, as: but be not limited only to 20:1,21:1,22:1,23:1,24:1,25:1,26:1,27:1,28:1,29:1,30:1,31:1,32:1,33:1,34:1,35:1,36:1,37:1,38:1,39:1 and 40:1.
The preparation method of active carbon composite nano-microsphere of the present invention, it has the active carbon composite nano-microsphere of water-wet behavior and organic dyestuff is mass ratio 20:1 ~ 80:1, prioritizing selection 40:1 ~ 60:1, as: but be not limited only to 40:1,41:1,42:1,43:1,44:1,45:1,46:1,47:1,48:1,49:1,50:1,51:1,52:1,53:1,54:1,55:1,56:1,57:1,58:1,59:1 and 60:1.
The preparation method of active carbon Nano microsphere of the present invention, activator as: but be not limited only to carbodiimide, dicyclohexylcarbodiimide, N-hydroxy-succinamide, maleimide, succimide, DMAP and DMF.These activators can independent or any several application and the present invention.
The invention provides in various technical scheme, coated material as: but be not limited only to chitosan, hyaluronic acid, Polyethylene Glycol, 3-aminopropyl triethoxysilane and ethyl orthosilicate.These coated materials can independent or any several application and the present invention.
The invention provides in various technical scheme, organic dyestuff as: but be not limited only to indocyanine green, isosulfan blue, methylene blue and patent blue.These organic dyestuff can independent or any several application and the present invention.
Various active carbon composite nano-microsphere provided by the invention, after being given biological subject body, can realize the confirmation of tumor boundaries, and lymphatic metastasis spike.Therefore, these active carbon Nano microspheres can be used as tracer, for the confirmation of tumor boundaries, and lymphatic metastasis spike.
The beneficial effect that technical solution of the present invention realizes:
Various active carbon composite nano-microsphere provided by the invention, there is very strong coloring, can multi-modal imaging be realized, and observe directly the trace of Nano microsphere from tumor, tissue or organ by naked eyes, its surface, also by being loaded with fluorescent dye, can realize fluorescence detection.
Various active carbon composite nano-microsphere provided by the invention, spike Be very effective, gives at once to represent obvious lymphatic tracer effect in biological subject body half an hour.
Various active carbon composite nano-microsphere provided by the invention, only need to adopt a small amount of reagent to obtain, method is easy, quick and efficient.
Accompanying drawing explanation
Fig. 1 is the transmission electron microscope figure of active carbon composite nano-microsphere of the present invention;
Fig. 2 is the electronogram of active carbon composite nano-microsphere of the present invention;
Fig. 3 is the mouse peritoneal position ordinary optical photo taken after nude mice omentum majus activated carbon injection composite nano-microsphere half an hour;
Fig. 4 is the fluorescence photo taken after nude mice omentum majus activated carbon injection composite nano-microsphere half an hour;
Fig. 5 behaves position, the abdominal cavity ordinary optical photo that omentum majus activated carbon injection composite nano-microsphere was taken after 20 minutes.
Detailed description of the invention
Technical scheme of the present invention is described in detail below in conjunction with accompanying drawing.The embodiment of the present invention is only in order to illustrate technical scheme of the present invention and unrestricted, although with reference to preferred embodiment to invention has been detailed description, those of ordinary skill in the art is to be understood that, can modify to the technical scheme of invention or equivalent replacement, and not departing from the spirit and scope of technical solution of the present invention, it all should be encompassed in right of the present invention.
Active carbon composite nano-microsphere involved by the present embodiment is produced all as follows
First active carbon is positioned over grinding in ball grinder, is put in water and leaves standstill two days, get upper strata suspension after taking-up, obtain active carbon Nano microsphere, its particle diameter is at 10nm ~ 100nm;
Then, with reference to the active carbon Nano microsphere obtained, 30:1 ~ 50:1 adds activator in molar ratio, stirs 20 minutes ~ 40 minutes, to activate further the carboxyl of activated carbon surface, and the active carbon Nano microsphere of obtained surface active;
Then, with reference to the activated carbon microballon obtaining surface active, 20:1 ~ 40:1 adds coated material in mass ratio, stirs 6 hours ~ 10 hours, the obtained active carbon composite nano-microsphere with water-wet behavior;
Finally, with reference to the active carbon complex microsphere with water-wet behavior, 40:1 ~ 60:1 adds organic dyestuff in mass ratio, with the obtained further compound of active carbon complex microsphere, and obtained active carbon composite nano-microsphere.
Wherein, activator is selected from one or more of carbodiimide, dicyclohexylcarbodiimide, N-hydroxy-succinamide, maleimide, succimide, DMAP and DMF.
Coated material is selected from one or more of chitosan, hyaluronic acid, Polyethylene Glycol, 3-aminopropyl triethoxysilane and ethyl orthosilicate.
Organic dyestuff is selected from one or more of indocyanine green, isosulfan blue, methylene blue and patent blue.
Obtained active carbon composite nano-microsphere is see Fig. 1 and Fig. 2.Indicated by Fig. 1 arrow, active carbon composite nano-microsphere is of a size of ~ 10nm, present comparatively rule spherical.As seen from Figure 2, diffraction spot is clear, and view picture figure is a set of diffraction spot, proves the single crystal characteristics of active carbon composite nano-microsphere.
Active carbon composite nano-microsphere is used for lymph node spike, specific as follows:
Gastric cancer situ tumor model is set up in advance to nude mice, gets the active carbon Nano microsphere solution of 10mg/mL, be injected in the omentum majus under gastric cancer tumor.As shown in Figure 3, after half an hour, clearly can find that lymph node becomes black (in figure arrow mark), spike successful.As indicated at 4, excite at 710nm wavelength laser, under the condition of 750nm wavelength absorption, except injection site, can also find that all there is fluorescence at omentum majus and other positions.Illustrate that active carbon Nano microsphere successfully spreads along lymphatic vessel.
Active carbon composite nano-microsphere is used for the lymphatic tracer of people, specific as follows:
Choose a Patients with Gastric Cancer, get the active carbon composite nano-microsphere solution of 10mg/mL, be injected in the omentum majus under gastric cancer tumor, as shown in Figure 5, after 20 minutes, clearly can find that lymph node becomes black (in figure arrow mark), illustrate that active carbon Nano microsphere successfully achieves spreading along lymphatic vessel in human body.

Claims (10)

1. an active carbon composite nano-microsphere, is characterized in that with particle diameter 10nm ~ 100nm activated carbon granule for carrier, at its surface recombination organic dyestuff.
2. an active carbon composite nano-microsphere, is characterized in that with particle diameter 10nm ~ 100nm activated carbon granule for carrier, and coated material is compound in described activated carbon granule surface, and organic dyestuff is compound in described coated material.
3. produce a method for the active carbon composite nano-microsphere described in claim 1 or 2, its step is as follows:
First active carbon is positioned over grinding in ball grinder, is put in water and leaves standstill two days, get upper strata suspension after taking-up, obtain active carbon Nano microsphere, its particle diameter is at 10nm ~ 100nm;
Then, add activator, stir 20 minutes ~ 40 minutes, to activate further the carboxyl of activated carbon surface, and the activated carbon microballon of obtained surface active;
Then, add coated material, stir 6 hours ~ 10 hours, the obtained active carbon complex microsphere with water-wet behavior;
Finally, add organic dyestuff, with the obtained further compound of active carbon composite nano-microsphere with water-wet behavior, and obtained active carbon composite nano-microsphere;
Described coated material is selected from one or more of chitosan, hyaluronic acid, Polyethylene Glycol, 3-aminopropyl triethoxysilane and ethyl orthosilicate.
4. the method producing active carbon composite nano-microsphere according to claim 3, is characterized in that described active carbon Nano microsphere and described activator are mol ratio 20:1 ~ 80:1.
5. the method producing active carbon composite nano-microsphere according to claim 3, is characterized in that the active carbon Nano microsphere of described surface active and coated material are mass ratio 20:1 ~ 80:1.
6. the method producing active carbon composite nano-microsphere according to claim 3, is characterized in that the described active carbon composite nano-microsphere with water-wet behavior and organic dyestuff are mass ratio 20:1 ~ 80:1.
7. the method producing active carbon composite nano-microsphere according to claim 3, it is characterized in that described activator is selected from one or more of carbodiimide, dicyclohexylcarbodiimide, N-hydroxy-succinamide, maleimide, succimide, DMAP and DMF.
8. the method producing active carbon composite nano-microsphere according to claim 3, is characterized in that organic dyestuff is selected from one or more of indocyanine green, isosulfan blue, methylene blue and patent blue.
9. the application of active carbon composite nano-microsphere as claimed in claim 1 or 2 in tumor boundaries confirms.
10. the application of an active carbon composite nano-microsphere as claimed in claim 1 or 2 in lymphatic metastasis spike.
CN201410468300.2A 2014-09-15 2014-09-15 Activated carbon nanosphere and application thereof to tumor boundary and lymph gland tracing Pending CN104208725A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201410468300.2A CN104208725A (en) 2014-09-15 2014-09-15 Activated carbon nanosphere and application thereof to tumor boundary and lymph gland tracing

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201410468300.2A CN104208725A (en) 2014-09-15 2014-09-15 Activated carbon nanosphere and application thereof to tumor boundary and lymph gland tracing

Publications (1)

Publication Number Publication Date
CN104208725A true CN104208725A (en) 2014-12-17

Family

ID=52090890

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201410468300.2A Pending CN104208725A (en) 2014-09-15 2014-09-15 Activated carbon nanosphere and application thereof to tumor boundary and lymph gland tracing

Country Status (1)

Country Link
CN (1) CN104208725A (en)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106822906A (en) * 2016-12-30 2017-06-13 四川大学 Water soluble acid responds lympha targeted slow-released carrier Nano carbon, preparation method and application
CN107260137A (en) * 2017-07-31 2017-10-20 济南显微智能科技有限公司 It is a kind of to detect ICG and double Tracing detection device and methods of methylenum careuleum simultaneously
CN108452323A (en) * 2017-02-21 2018-08-28 中国科学院宁波材料技术与工程研究所 A kind of nanocomposite and its application in tracer lymph node
CN111218127A (en) * 2020-01-07 2020-06-02 山东大学齐鲁医院 Near-infrared fluorescent dye and preparation method and application thereof
WO2022041802A1 (en) * 2020-08-26 2022-03-03 成都纽瑞特医疗科技股份有限公司 Zirconium carbon microsphere suspension, preparation method therefor and use thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1548367A (en) * 2003-05-16 2004-11-24 中国人民解放军军事医学科学院毒物药 Nano level active carbon and its prepn and use

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1548367A (en) * 2003-05-16 2004-11-24 中国人民解放军军事医学科学院毒物药 Nano level active carbon and its prepn and use

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
夏飞麟: "纳米碳注射液对肝癌切缘及淋巴引流示踪的实验研究", 《中国优秀硕士学位论文全文数据库-医药卫生科技辑》, 15 October 2009 (2009-10-15) *
宋东颖: "纳米活性碳吸附丝裂霉素对人肝癌Huh-7肿瘤肝细胞抑制作用的研究", 《中国优秀硕士学位论文全文数据库医药卫生科技辑》, 15 September 2013 (2013-09-15) *
张帅: "石墨烯基纳米材料的合成、表征在生物中的应用", 《中国优秀硕士学位论文全文数据库-工程科技Ⅰ辑》, 15 October 2012 (2012-10-15) *
陈素玉: "淋巴示踪技术在消化道早癌诊疗中的应用进展", 《微创医学》, 25 December 2013 (2013-12-25) *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106822906A (en) * 2016-12-30 2017-06-13 四川大学 Water soluble acid responds lympha targeted slow-released carrier Nano carbon, preparation method and application
CN106822906B (en) * 2016-12-30 2020-08-04 四川大学 Water-dispersible acid-responsive lymph-targeting slow-release carrier nano-carbon, preparation method and application
CN108452323A (en) * 2017-02-21 2018-08-28 中国科学院宁波材料技术与工程研究所 A kind of nanocomposite and its application in tracer lymph node
CN107260137A (en) * 2017-07-31 2017-10-20 济南显微智能科技有限公司 It is a kind of to detect ICG and double Tracing detection device and methods of methylenum careuleum simultaneously
CN111218127A (en) * 2020-01-07 2020-06-02 山东大学齐鲁医院 Near-infrared fluorescent dye and preparation method and application thereof
CN111218127B (en) * 2020-01-07 2022-03-08 山东大学齐鲁医院 Near-infrared fluorescent dye and preparation method and application thereof
WO2022041802A1 (en) * 2020-08-26 2022-03-03 成都纽瑞特医疗科技股份有限公司 Zirconium carbon microsphere suspension, preparation method therefor and use thereof

Similar Documents

Publication Publication Date Title
CN104208725A (en) Activated carbon nanosphere and application thereof to tumor boundary and lymph gland tracing
Wang et al. Large hollow cavity luminous nanoparticles with near-infrared persistent luminescence and tunable sizes for tumor afterglow imaging and chemo-/photodynamic therapies
Yang et al. Surgical navigation for malignancies guided by near‐infrared‐II fluorescence imaging
Song et al. Repeatable deep-tissue activation of persistent luminescent nanoparticles by soft X-ray for high sensitivity long-term in vivo bioimaging
Ai et al. Near infrared-emitting persistent luminescent nanoparticles for hepatocellular carcinoma imaging and luminescence-guided surgery
Chen et al. Preparation and photodynamic therapy application of NaYF4: Yb, Tm–NaYF4: Yb, Er multifunctional upconverting nanoparticles
CN103143035B (en) Application of heteroatoms doped aqueous carbon quantum dot in preparation of photo-sensitizers for fluorescent imaging marking and photodynamic therapy (PDT)
CN105251420B (en) A kind of preparation method of multi-functional complex microsphere
CN103480006A (en) Preparation method and application for multifunctional nanometer diagnosis and treatment agent integrating light emitting/CT/MR multi-mode imaging and tumor hyperthermia
Jin Critical review—recent progress in NIR fluorophores emitting over 1000 nm for bioimaging
CN106344937A (en) Monolayer molybdenum disulfide-cobalt ferrite nanocomposite material as well as preparation method and application thereof
CN104083779A (en) Near-infrared light/ultrasonic dual-mode lymph node targeting contrast agent and its preparation method and use
CN104491882A (en) Copper sulphide nanoparticle diagnosis agent used as photoacoustic imaging contrast agent and photo-thermal therapeutic agent and preparation method of copper sulphide nanoparticle diagnosis agent
Lin et al. Near‐Infrared Persistent Luminescence Nanoprobe for Ultrasensitive Image‐Guided Tumor Resection
CN104483296A (en) Breast cancer molecular probe and preparation method thereof
CN108721617A (en) A kind of preparation method of multi-functional conjugated highpolymer gel based composites
CN108187048A (en) A kind of photo-thermal-optoacoustic-magnetic resonance diagnosis and treatment reagent and preparation method thereof
CN104940958A (en) Fluorescent magnetic nano targeted medicine and preparation method thereof
CN104998301A (en) Preparation method of carbon nano tube reinforced mesoporous hydroxyapatite composite material
CN109276538A (en) A kind of photothermal response carries the design synthetic method of liquid medicine gel
Wang et al. An optimized lanthanide-chlorophyll nanocomposite for dual-modal imaging-guided surgery navigation and anti-cancer theranostics
CN109589408A (en) A kind of meter of shape liquid metal nanoparticle and its synthetic method and application
CN104117074A (en) Therapy diagnosis preparation based on polypyrrole compound and preparation method of preparation
CN104288793B (en) Nanometer ultrasonic fluorescebimodal bimodal contrast preparation, its preparation method and application
CN209790636U (en) Tumor positioning and marking device

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
WD01 Invention patent application deemed withdrawn after publication

Application publication date: 20141217

WD01 Invention patent application deemed withdrawn after publication