CN107121550A - Utilize application of the sulfonic group graphene quantum dot cell nucleus targeting characteristic in detection liver cancer tissue cell in situ - Google Patents

Utilize application of the sulfonic group graphene quantum dot cell nucleus targeting characteristic in detection liver cancer tissue cell in situ Download PDF

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CN107121550A
CN107121550A CN201710286296.1A CN201710286296A CN107121550A CN 107121550 A CN107121550 A CN 107121550A CN 201710286296 A CN201710286296 A CN 201710286296A CN 107121550 A CN107121550 A CN 107121550A
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gqds
liver cancer
situ
cell
quantum dot
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王艳丽
姚晨婕
丁琳
李晨晨
章康康
吴明红
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University of Shanghai for Science and Technology
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University of Shanghai for Science and Technology
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/531—Production of immunochemical test materials
    • G01N33/532—Production of labelled immunochemicals
    • G01N33/533—Production of labelled immunochemicals with fluorescent label
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574—Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407—Specifically defined cancers
    • G01N33/57438—Specifically defined cancers of liver, pancreas or kidney

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Abstract

The present invention relates to a kind of application of utilization sulfonic group graphene quantum dot cell nucleus targeting characteristic in detection liver cancer tissue cell in situ.Sulfonic group graphene quantum dot is injected into after liver cancer model, 0.5 h by 30 200 mg/kg, sections observation GQDs is distributed in tumor tissues.The present invention being capable of effective district point tumor tissue cell, normal tissue cell and its cancer beside organism's cell in animal liver cancer model in situ and human hepatocellular model using graphene quantum dot (GQDs)；Efficient, sensitive infantile tumour detection can be realized（Tumour is long, is wider than and can detect equal to 5 mm）；With it is simple to operate, be quick on the draw, effect is obvious, the advantage such as with low cost.

Description

Using sulfonic group graphene quantum dot cell nucleus targeting characteristic in detection liver cancer group in situ Knit the application in cell
Technical field
The present invention relates to one kind using sulfonic group graphene quantum dot cell nucleus targeting characteristic in detection liver cancer tissue in situ Application in cell.
Background technology
Liver cancer, is clinically one of most common malignant tumour, and its form is divided into nodular type, massive type and diffuses type.For Good therapeutic effect is reached, being accurately positioned for tumour is particularly important.At present, in therapeutic field of tumor, many researchers Research high performance material is all directed to as tracer, using the feature of tumor tissue specificity, by tumor tissues and normal group Knit and accurately distinguish out, judge prognosis and select appropriate therapeutic scheme, so as to improve the effect of follow-up oncotherapy, face with important Bed application value.
At present, it is exactly using these features such as tumor hypoxia, ischemics, using such as nitro miaow to study more neoplasm tracing agent The energy selective aggregation such as azole compounds connects radionuclide in the material of Fa Yang ischemic tissues, to tumor hypoxia imaging, So as to improve tumour radiotherapy and chemotherapeutic treatment effect.In addition, rarely material can be widely applied on a large scale generally Lesion detection.
The content of the invention
It is former in detection using sulfonic group graphene quantum dot cell nucleus targeting characteristic it is an object of the invention to provide one kind Application in position liver cancer tissue cell, normal tissue cell and cancer beside organism's cell
The sulfonic group graphene quantum dot (GQDs) that the present invention is used is a kind of high-performance fluorescent material, sulfonic group graphene quantum Point (GQDs) can be with selectively targeted neoplastic cell nuclei, so as to distinguish tumor tissues, cancer beside organism and normal structure.Preparation method Refer to Chinese patent：201510394852.8, sulfonic group graphene quantum dot biological fluorescent labeling and its application.It can not penetrate just Normal cell membranes in tissue；And in tumor tissues, GQDs readily penetrates through cell membrane, marked tumor nucleus is targetted.We are in the original location Found in liver cancer model, GQDs is largely gathered in tumor tissues, sections observation finds that GQDs can accurately distinguish canceration group in addition Knit and normal structure, and interface is obvious.Suitable for non-invasive tumor Image Location, be conducive to follow-up diagnosing tumor and control Treat.
Liver tumour histocyte is efficiently targetted in liver cancer model in the original location
Study GQDs and ability is targetted to tumor tissue specificity, by setting up mouse liver cancer model in situ, by 30-200 mg/kg Sulfonic group graphene quantum dot is injected into after liver cancer model, 0.5 h, sections observation GQDs is distributed in tumor tissues, in vivo Tumor locus on special target hepatic tissue immediately, very small amount is present in after other normal structures, and 96 h most of from body Intracellular metabolite comes out, in vivo low toxicity.
Tumor tissues and cancer beside organism interface can accurately be recognized
GQDs embodies very sensitive pressure-responsive in animal liver cancer model, and liver cancer accurate inspection in situ can be realized as probe Survey.GQDs (30-200 mg/kg) is injected intravenously into liver cancer animal model in situ and the in vitro liver cancer human mould of in-situ injection After type, 0.5 h, observation section finds GQDs special target tumor tissues, and highly efficient labeling tumor tissue cell core.Tumor tissues And the interface of cancer beside organism is clear, can be clearly observable in intensive tumor tissues, the selectively targeted neoplastic cell nucleis of GQDs, And be distributed in loose cancer beside organism, GQDs is in normal liver tissue interstitial dispersed distribution.To the in vitro liver cancer model of people and dynamic Thing liver cancer model recognition capability is all good.
Tumor tissue cell, normal tissue cell and its cancer beside organism's cell can be accurately distinguished, it is possible to achieve early stage is swollen Knurl is detected
In addition, GQDs (30-200 mg/kg) is injected intravenously in different volumes liver cancer animal model in situ, after 0.5 h, Detect in different volumes liver cancer tissue, GQDs distribution situations in tumour, cancer side and hepatic tissue.It was found that GQDs is in liver cancer tissue Aggregation also with gross tumor volume positive correlation, illustrate GQDs specificity differentiation tumor tissues it is functional.And during observation section is found, swell Knurl volume>66 mm3When, GQDs specific accumulation neoplastic cell nucleis can also target the tumour that sporadicly exists thin in cancer beside organism Karyon, and normal tissue cell core can not be entered, illustrate that GQDs can accurately distinguish tumour, cancer and take up normal structure；Tumour body Product is in 66 mm3When, 5 mm a width of equivalent to tumour length, you can detect tumour efficient and sensible.Demonstrating GQDs can also make The early detection of liver cancer is carried out for probe.
The advantage and feature of the inventive method are as described below:
(1) GQDs is selectively targeted to tumor cell of liver core, accurately distinguishes normal liver tissue and cancer beside organism.Knowledge is marked Method for distinguishing is simple, low toxicity, high fluorescent, it is not necessary to carry out secondary modification to material
(2) GQDs can realize efficient, sensitive infantile tumour detection
(3) it is simple to operate, be quick on the draw, effect it is obvious.
Brief description of the drawings
Fig. 1 sulfonic groups graphene quantum dot (GQDs) is distributed in mouse liver cancer model internal organs in situ.a：Intravenous injection After 0.5 h and 96 h, GQDs distribution situations in animal model different organs.b：Fluorescence intensity signals are counted in GQDs internal organs.
Fig. 2 GQDs are in human hepatocellular model and rat liver cancer model median surface distribution situation；a：GQDs in-situ injections 0.5 After h, in two different gross tumor volume human hepatocellular samples, distribution situation is detected, can be with efficient identification tumour and cancer beside organism. b：After the h of GQDs in-situ injections 0.5, in two different mice with tumor liver cancer samples, distribution situation is detected, can be with efficient identification Tumour and cancer beside organism.Scale：10 µm.
Fig. 3 GQDs original position efficient identification liver cancer and normal liver tissue；It is injected intravenously after the h of GQDs 0.5, detection GDQs exists In the mouse of different gross tumor volumes liver cancer sample in situ, by tumour, cancer, distribution situation difference in normal hepatocytes.Scale：10 µm.
In the liver cancer model of Fig. 4 mouse original position, the relation of gross tumor volume and GQDs distribution situations.Mouse original position liver cancer model It is interior, gross tumor volume and GQDs distribution situations in liver.a：GQDs intravenous injections enter after mouse liver cancer model in situ, intra-tumor letter Number distribution and the relation of gross tumor volume；b：GQDs tail vein injections enter after mouse liver cancer model in situ, in liver signal distributions with The relation of gross tumor volume.
Embodiment
The resume method that the specific embodiment of the present invention now is described in into rear liver cancer model in situ is referred to：[1]
Embodiment 1：GQDs efficient targeting liver tumour histocytes in liver cancer model in the original location：
Experiments of the GQDs to fluorescent dye with tumour-specific targeting ability, by setting up mouse liver cancer model in situ, every other day by GQDs (30-200 mg/kg) is injected intravenously into animal model, 0.5 h, after 96 h, is taken out the heart, liver+tumour, spleen, lung, kidney, brain, is put In GQDs fluorescence intensities in living imaging observation internal organs, and fluorescence intensity is counted.Research shows GQDs pairs of pressure-responsive Tumor tissues have after selectively targeted ability, 0.5 h, in vivo tumor locus immediately on special target hepatic tissue, very small amount It is present in major part after other normal structures, and 96 h to come out from internal metabolism, in vivo low toxicity.Concrete outcome is referring to figure 1。
Embodiment 2：GQDs can accurately recognize tumor tissues and cancer beside organism interface
Experiments of the GQDs to fluorescent dye with tumour-specific targeting ability, will by animal liver cancer model in situ and human hepatocellular model GQDs (30-200 mg/kg) is injected intravenously to be entered after human hepatocellular model, 0.5 h into animal model or in-situ injection, section Observation GQDs is distributed in tumor tissues.We find the interface locations of tumor tissues and cancer beside organism, can be clearly observable In intensive tumor tissues, the selectively targeted neoplastic cell nucleis of GQDs, and be distributed in loose cancer beside organism, GQDs is normal Hepatic tissue interstitial dispersed distribution, and be sporadicly present in a small amount of neoplastic cell nuclei.Show that GDQs can be efficiently by tumor group Knit and made a distinction with other tissue specificities, it is adaptable to clinical research.Concrete outcome is referring to Fig. 2.
Embodiment 3：GQDs can accurately distinguish tumor tissue cell, normal tissue cell and its cancer beside organism's cell, can To realize that infantile tumour is detected：
GQDs embodies very sensitive gross tumor volume response in animal liver cancer model, can realize that liver cancer is in situ accurate as probe Detection identification.The relation assembled for research tumor size and GQDs in intra-tumor, we are by different volumes hepatic carcinoma tissue, cancer After side tissue and normal structure are taken out, the freezing microtome section sample of 20 μ m-thicks is made in tissue sample, for carrying out laser co-focusing Micro- sem observation GQDs distribution situations in tumor tissues and normal liver tissue.Detection finds tumour, cancer beside organism and normal GQDs distribution situation is relevant with gross tumor volume in tissue, and aggregations of the GQDs in liver cancer tissue and gross tumor volume positive correlation, Illustrate that GQDs specificity distinguishes tumor tissues functional.And during observation section is found, gross tumor volume>66 mm3When, quite In a width of 5 mm of tumour length, GQDs specific accumulation neoplastic cell nucleis can also target the tumour that sporadicly exists thin in cancer beside organism Nucleus is cannot be introduced into karyon, normal structure, in interstitial dispersed distribution, illustrates GQDs neoplastic cell nuclei Targeting Effect spirit It is quick.Demonstrating GQDs can also detect as probe application in early liver cancer, efficient identification cancer beside organism and normal structure interface. Concrete outcome is referring to Fig. 3,4.
Bibliography：
[1] Li Yinpeng, Zhu Huiming, the foundation of this magnificent C57B L/6J mouse of Wu liver cancer model in situ and high frequency ultrasound are to original position Monitoring [J] the gastroenterologies and hepatopathy magazine of cancer, 2010,19 (2):145-147.

Claims (1)

1. a kind of application of utilization sulfonic group graphene quantum dot cell nucleus targeting characteristic in detection liver cancer tissue cell in situ.
CN201710286296.1A 2017-04-27 2017-04-27 Utilize application of the sulfonic group graphene quantum dot cell nucleus targeting characteristic in detection liver cancer tissue cell in situ Pending CN107121550A (en)

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108519359A (en) * 2018-03-29 2018-09-11 上海大学 The method that the visualization tracking of tumour cell is carried out using graphene quantum dot
CN110453378A (en) * 2019-07-03 2019-11-15 上海大学 A kind of sulfonic acid based quantum dot/fibroin albumen composite nano-fiber membrane and its preparation method and application
NL2032008B1 (en) * 2022-05-27 2023-12-12 Yian Medical Tech Zhejiang Co Ltd Fluorescent labeling kit for a tumor cell nucleus and labeling method thereof

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105106974A (en) * 2015-07-08 2015-12-02 上海大学 Sulfonated graphene quantum dot bioluminescence probe and application thereof

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105106974A (en) * 2015-07-08 2015-12-02 上海大学 Sulfonated graphene quantum dot bioluminescence probe and application thereof

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108519359A (en) * 2018-03-29 2018-09-11 上海大学 The method that the visualization tracking of tumour cell is carried out using graphene quantum dot
CN110453378A (en) * 2019-07-03 2019-11-15 上海大学 A kind of sulfonic acid based quantum dot/fibroin albumen composite nano-fiber membrane and its preparation method and application
NL2032008B1 (en) * 2022-05-27 2023-12-12 Yian Medical Tech Zhejiang Co Ltd Fluorescent labeling kit for a tumor cell nucleus and labeling method thereof

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Application publication date: 20170901