CN101972484A - Novel method of early cancer diagnosis based on gold nanorod - Google Patents
Novel method of early cancer diagnosis based on gold nanorod Download PDFInfo
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- CN101972484A CN101972484A CN2010105064887A CN201010506488A CN101972484A CN 101972484 A CN101972484 A CN 101972484A CN 2010105064887 A CN2010105064887 A CN 2010105064887A CN 201010506488 A CN201010506488 A CN 201010506488A CN 101972484 A CN101972484 A CN 101972484A
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Abstract
The invention belongs to the field of nano-biomedicine. The traditional early cancer diagnosis has the defects of low sensitivity, high cost, inconvenient use, and the like. The surface enhanced Raman scattering technology of gold nanorods can realize the sensitivity of single molecule detection. In the invention, by using the strong absorption characteristic of cancer cells for the gold nanorods, the gold nanorods are collected in a tumor tissue through intravenous injection, Raman probe molecules are attached to the surfaces of the gold nanorods, and the early-period and high-sensitivity detection of cancers is realized by measuring a Raman spectrum of the Raman probe molecules. Absorption peaks of the selected gold nanorods are in a near-infrared wave band, thereby pump light and scattered light can be easy to enter and perforate a human body. The invention provides a novel, efficient and convenient method for the clinical diagnosis of early cancers.
Description
Affiliated technical field
This patent belongs to the nano biological medical domain.The early diagnosis that is used for tumor and cancer, the tumor in diagnosable epithelial tissue tumor and the part organ, range of application comprises: skin carcinoma, oral cancer, esophageal carcinoma, gastric cancer, intestinal cancer, breast carcinoma, cervical cancer etc.
Background technology
Be the means that adopt medical pathologies to detect to the standard method of cancer diagnosis clinically at present: the lesions position flesh tissue of excision is made into section, examine under a microscope after the dyeing, but this method limitation is very big: this diagnostic method length consuming time, and testing result has certain subjectivity: to same basal cell carcinoma case, the identical rate of the testing result that the conclusion that single pathology expert draws and other experts draw only is 65%.Therefore, need a kind of new detection method that rapid and objective diagnostic message can be provided clinically, this will improve the speed and the accuracy of pathological diagnosis greatly.
Raman spectrum is one of important means of analyzing molecules structure, and it is referred to as " finger print region of molecule ", and the Raman scattering technology has begun to be applied in the research aspect health check-up survey and Raman imaging of biological tissue, and wherein two most important distinct advantages are:
1. the excitaton source of Raman spectrum can be positioned near infrared band, and this scope is the optical window of biological tissue, and is littler two more than the order of magnitude (as shown in Figure 2) than the absorptance of fluorescence wave band commonly used at the absorptance of this wave band biological tissue;
2. can adopt surperficial enhancement techniques, improve the sensitivity that Raman spectrum is surveyed at body.Surface enhanced raman spectroscopy (Surface Enhanced Raman Spectroscopy) be meant when Molecular Adsorption at inert metal (as gold, silver etc.) in the time of on the rough surface, its raman scattering cross section or scattering coefficient can increase by 5 to 6 orders of magnitude, if in " focus " position, then might increase by 14 orders of magnitude.Just reached the sensitivity of single-molecule detection in the nineties, utilize gold nanorods etc. to do substrate in recent years, entered the research of subcellular fraction environment SERS, these are surveyed at body and have embodied the application potential of Raman scattering technology as the hypersensitivity Measurement for Biotechnique.
2009, state federal professor Torres of university in Virginia the has utilized raman study hemoglobin cell of transgenic white mouse reaping hook cell; Professor Andrew of University of Leeds utilizes the diversity of the human thyroid cell of raman study and has set up accurate model.
2010, the Suneetha of astrophysics institute of Wayne State University analyzed optimum epithelial cell, two kinds of main diversityes of the Raman spectral characteristics of prostatic intraepithelial neoplasm formation and prostate gland cancer cell: the intensity difference opposite sex of specific band; The Raman shift of specific band.Diversity quantitative classification with Raman spectrum becomes 6,7 and 8 grades of carcinoma of prostate Gleason scorings afterwards.This research indicates that Raman spectrum can come the different lesions stage of diagnosing prostate cancer according to the content of different biotic components.Hawaii doctor Lori of DKFZ of state university in 2010 by the cell in vitro Study on tissue culture Raman spectrum diversity of optimum squamous cell and human body cervical carcinoma cell.Result of study shows that there is significant difference in raman spectrum strength between the two, for example at wave number 2800cm
-1To 3100cm
-1The zone, the crest of the c h bond stretching vibration spectrum place correspondence of cancerous cell is than low six orders of magnitude of normal cell.
The present invention adopts laser technology, nanotechnology and biotechnology to combine, and is a kind of new early diagnosis of cancer method.Gold nanorods has had perfect chemical preparation process, and we have produced all kinds of gold nanorods, and not only draw ratio is controlled, and size can prepare for a short time of 5nm, and surface combination has Raman microprobe molecule and surfactant, can preserve for a long time; 700nm also is a kind of mature technique to the laser of 900nm, can buy by market to obtain.In conjunction with our previous work, comprise cell experiment, experiment on mice and monkey experiment, illustrate that the present invention can realize.
Advantages such as the present invention has that diagnosable tumor kind is many, and toxic and side effects is little, and sense cycle is short, and is can be handling strong are one of effective ways of early diagnosis of cancer.
Summary of the invention
We select 3.3 ' diethyl thioaldehydes tricarbocyanine iodine (3.3 '-diethylthiatricarbocyanine iodide chemical formula C
25H
25IN
2S
2Be called for short DTTC) as the Raman microprobe molecule (as shown in Figure 3) that is attached on the gold nanorods, according to the characteristics of cancerous cell " irrational growth ", the gold nanorods that is injected into human body can be absorbed and be stored in lesion tissue (48～72 hours) rapidly by cancerous cell.Then, with near infrared band Raman excitation light source irradiating and detecting zone, promptly can obtain the spectral line (as shown in Figure 4) of the enhanced Raman microprobe molecule of gold nanorods DTTC, thereby realize the early diagnosis of tumor.Gold nanorods in normal structure and the body fluid will excrete after 72 hours along with urine and feces.
Description of drawings
Fig. 1 is the abosrption spectrogram of the gold nanorods of the gold nano ball of different size and different draw ratios;
Fig. 2 is at the absorptance of near infrared band biological tissue little two comparison diagrams more than the order of magnitude of absorptance than fluorescence wave band commonly used;
Fig. 3 is the gold nanorods sketch map that surface combination has surfactant CTAP and Raman microprobe molecule DTTC;
Fig. 4 surveys optical wavelength 632.8nm, and DTTC is at wave-number range 550-1800cm during time of exposure 100s
-1The comparison diagram of the SERS of the SERS of the SERS of place's gold nanorods, the gold nanorods of attaching surface activating agent and the pure level of liquid chromatograph water;
Fig. 5 is the cancer diagnosis procedure chart;
The specific embodiment
Further set forth the specific embodiments of invention below in conjunction with embodiment.
1, selected 3.3 ' diethyl thioaldehydes tricarbocyanine iodine (3.3 '-diethylthiatricarbocyanine iodide chemical formula C
25H
25IN
2S
2Be called for short DTTC) as SERS active probe molecule configuration gold nanorods solution;
2, human body is gone in gold nanorods solution (solution and body weight ratio are 1: 1000) intravenous injection;
3, after 48～72 hours, gold nanorods in the cancer cell tissue of lesions position enrichment get up;
4, adopt Raman spectrometer that patient's suspected abnormality position is detected, carry out repeatedly duplicate detection for the obvious zone of detectable signal;
5, the Raman spectrum data of acquisition Raman spectrum and Raman microprobe molecule DTTC is compared, the state of an illness of sufferer is made a definite diagnosis.
6, the drainage phase: after injection 72 hours, the most of gold nanorods in the normal structure will excrete by urine and feces.
Claims (5)
1. new method based on the gold nanorods early diagnosis of cancer, it is characterized in that: pass through vein, there is the gold nanorods of Raman microprobe molecule to be injected into human body surface combination, gold nanorods enrichment in tumor is got up, by surveying the Surface enhanced raman spectroscopy spectrum of gold nanorods surface Raman microprobe molecule, realize the early diagnosis of tumor.
2. gold nanorods according to claim 1, it is characterized in that choosing diameter is 5-7nm, and draw ratio is the gold nanorods of 2-5, and its absorption spectra is positioned near infrared band (as shown in Figure 1), its surface combination surfactant CTAP and Raman microprobe molecule DTTC.
3. according to claim 1, the intravital gold nano particle colloidal sols of sufferer is gone in intravenous injection and patient anharmonic ratio example is 10-100Mg/Kg.
4. according to claim 1, gold nanorods colloidal sol the patient internal recycle after 48～72 hours in the cancerous cell at lesions position enrichment get up, the gold nanorods colloidal sol in the normal structure excretes by urine and feces.
5. according to claim 1, the excitation source of Raman spectrum is selected the near infrared band that good transmitance is arranged for use in tissue.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102793932A (en) * | 2012-09-04 | 2012-11-28 | 长春鸿特生物科技有限公司 | Application of gold nanorods |
| CN103257133A (en) * | 2013-04-18 | 2013-08-21 | 上海交通大学 | Preparation method and application of mercury ion detection probe |
-
2010
- 2010-10-14 CN CN2010105064887A patent/CN101972484A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102793932A (en) * | 2012-09-04 | 2012-11-28 | 长春鸿特生物科技有限公司 | Application of gold nanorods |
| CN103257133A (en) * | 2013-04-18 | 2013-08-21 | 上海交通大学 | Preparation method and application of mercury ion detection probe |
| CN103257133B (en) * | 2013-04-18 | 2015-10-14 | 上海交通大学 | Detect the preparation method and its usage of mercury ion probe |
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Open date: 20110216 |