CN102698294A - Chitosan-supported hydroxycamptothecine-quantum dot FRET (Fluorescence Resonance Energy Transfer) composite probe - Google Patents
Chitosan-supported hydroxycamptothecine-quantum dot FRET (Fluorescence Resonance Energy Transfer) composite probe Download PDFInfo
- Publication number
- CN102698294A CN102698294A CN2012102166407A CN201210216640A CN102698294A CN 102698294 A CN102698294 A CN 102698294A CN 2012102166407 A CN2012102166407 A CN 2012102166407A CN 201210216640 A CN201210216640 A CN 201210216640A CN 102698294 A CN102698294 A CN 102698294A
- Authority
- CN
- China
- Prior art keywords
- quantum dot
- fret
- hydroxycamptothecine
- chitosan
- hydroxy camptothecin
- 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
Links
Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
The invention provides a chitosan-supported hydroxycamptothecine-quantum dot FRET (Fluorescence Resonance Energy Transfer) composite probe. In the probe, a quantum dot with a certain wavelength is coupled with hydroxycamptothecine serving as an anticancer medicament, so that a composite structure with a fluorescence resonance energy transfer characteristic is formed; and the composite probe with an FRET characteristic is expressed under the excitation of ultraviolet light or visible light. The composite probe has the beneficial effects: energy is transferred onto hydroxycamptothecine by establishing a hydroxycamptothecine-quantum dot FRET composite structure, so that the fluorescence intensity of hydroxycamptothecine is increased, and a fluorescence in-situ expression characteristic for reacting with cancer cells is realized; the acting process and distribution rule of the composite probe in each region of a tumor cancer cell are observed through the fluorescence action of the composite probe in a targeted delivery process; and the FRET system of the composite probe is damaged in the releasing and tumor cancer cell acting processes of hydroxycamptothecine, the fluorescence of a quantum dot is recovered gradually, and in-situ real-time dynamic monitoring of the acting process of hydroxycamptothecine and tumor cancer cells can be realized indirectly by monitoring information such as the fluorescence intensity change magnitude, change rate and the like of the quantum dot.
Description
Technical field
The present invention relates to chemistry and biotechnology crossing domain, particularly a kind of chitosan props up and carries hydroxy camptothecin-quantum dot FRET combined probe.
Background technology
As everyone knows, cancer is that human life's threatens greatly, and the real-time monitoring that how to realize effective treatment and the treatment curative effect of cancer becomes one of problem that scholars pay close attention to most.
At present, are chemotherapy for the most frequently used means of cancer, cancer therapy drug can duplicate through suppressing DNA (DNA), and the division of blocking-up cancerous cell, thereby the growth of anticancer are to reach the treatment curative effect.But chemotherapeutics is generally not single-minded; In kill cancer cell; Also can exert an influence to Normocellular cell division; Injury need be divided with the health tissues of keeping normal function and cell, for example hair base portion cell and intestinal mucosa cells etc., thus make patient that symptoms such as alopecia and nausea and vomiting often arranged.
Simultaneously; Normally used therapeutic evaluation standard to solid tumor is RECIST (Response Evaluation Criteria in Solid Tumors now; RECIST) and WHO; Estimate the advancing of disease situation through the major diameter dimensional variation of tumor before and after the treatment, its evaluation index mainly contains: alleviate (CR) fully, part is alleviated (PR), stable disease (SD), PD (PD).Other detection meanss; (be applicable to body surface or shallow-layer like chest X ray (being applicable to pulmonary), computed tomography (CT), NMR-imaging (MRI), ultrasound investigation; Be not suitable for the abdominal cavity), cytology and histological examination means such as endoscope and peritoneoscope, tumor marker; To the tumor change procedure also is a kind of static portrayal, is difficult to realize the original position Real-Time Evaluation of cancer drug therapy curative effect, and the drug effect therapeutic evaluation has certain hysteresis quality.
Delivering medicine to tumor cancerous cell focus targeting is one of effective ways of effectively treating cancer, and it can overcome the side effect that chemotherapy brings.This system can be transported to the target area to greatest extent with medicine; Medicine is concentrated in the target area, can exceed several times and even hundreds of times of general reagent, directly act on pathological tissues, organ and cell; The action time of prolong drug and target site, therapeutic effect obviously improves; Simultaneously can reduce drug dose, reduce the concentration of medicine, reach the therapeutic effect of high-efficiency low-toxicity at other positions.In addition; In numerous treatment of solid tumors method for estimating curative effect; The isotope detection method that the fluorescent probe method is more traditional is compared, and the speed that shows is fast, good reproducibility, consumption reach advantages such as radiationless less, is used widely at aspects such as medical diagnosis on disease, cancer therapy drug analysis, antibody immunoassays.With the specific effect entering tumor cell of the link coupled fluorophor of folate molecule, tumor tissues obviously is different from closes on normal structure through folacin receptor.With the radiophotography compared with techniques, fluorescence imaging does not have wound, makes human body avoid particle radiation yet.
FRET (FRET) is a kind of novel fluorescence research method; Because FRET is sensitive for the spatial orientation height of distance and fluorophor; Can observe the change situation of biomolecule interphase interaction through the measurement of FRET efficient, react the range information of two micels.Theoretically, any biological mechanism of research can be through the FRET technology on molecular level, and key is to find suitable fluorescent probe.Hydroxy camptothecin is that a kind of anticancer spectrum is wider, and the antineoplastic agent that toxicity is little itself has certain fluorescent characteristic, and its excitation wavelength is 363nm, and emission wavelength is 550nm.Because its fluorescence quantum yield is low, fluorescence intensity is not high, the function that does not possess the while kill cancer cell and express with the cancerous cell fluorescent in situ.And quantum dot (Quantum Dots; Be called for short QDs) as a kind of fluorescence semiconductor material,, it make it in the application of FRET, have a lot of advantages because of having fluorescence emission spectrum peak spectral quality narrow and symmetrical, that have broad to get excellences such as excitation of spectra scope, emission wavelength tunable and bleach-resistant property are strong.Select the quantum dot of suitable wavelength; And it and hydroxy camptothecin is coupling on the identical carrier; The two can form FRET to make them, strengthens fluoroscopic examination sensitivity, when can be implemented in hydroxy camptothecin and kill cancerous cell; Real-time fluorescence is expressed cancerous cell effect form, realizes the original position real-time dynamic monitoring of hydroxy camptothecin and tumor cancerous cell mechanism and treatment curative effect.
Summary of the invention
The present invention provides a kind of chitosan to prop up and carries hydroxy camptothecin-quantum dot FRET combined probe; Quantum dot and anticarcinogen hydroxy camptothecin that this probe will have certain wavelength are coupled; Formation has the composite construction of FRET (FRET) characteristic; Excite the fluorescent probe of expressing the FRET characteristic down at ultraviolet light or visible light quantity, adopt folic acid that this probe is modified and be built into the hydroxy camptothecin-quantum dot FRET fluorescent probe of a kind of targeting in the tumor cancerous cell.Utilize the specificity binding characteristic of folic acid and folacin receptor to realize targeting labelling to the tumor cancerous cell; Utilize the FRET characteristic between the hydroxy camptothecin and quantum dot on the probe; In probe and carninomatosis kitchen range mechanism; The observation of FRET phenomenon structural change information and quantum dot fluorescence image change, the original position real-time dynamic monitoring of realization fluorescent probe and tumor cancerous cell interaction process and efficient.
For realizing above-mentioned purpose, the present invention adopts technical scheme to provide a kind of chitosan and props up a year hydroxy camptothecin-quantum dot FRET combined probe, and wherein: this combined probe comprises chitosan, quantum dot and the anticarcinogen hydroxy camptothecin of modified with folic acid; Said quantum dot is for having certain wavelength; Can be coupled as energy donor and anticarcinogen hydroxy camptothecin; Formation has the combined probe structure of FRET (FRET) characteristic; Under ultraviolet light or excited by visible light, can shift with hydroxy camptothecin generation photoelectricity and fluorescent quenching takes place, and excited energy is transferred on the hydroxy camptothecin and one type of water-soluble quantum dot of expressing the FRET characteristic.
Effect of the present invention is:
1. a kind of chitosan of the present invention props up and carries hydroxy camptothecin-quantum dot FRET combined probe; Made up hydroxy camptothecin-quantum dot FRET combined probe structure, under ultraviolet light or excited by visible light, quantum dot and hydroxy camptothecin generation photoelectricity shift; Quantum dot generation fluorescent quenching; And excited energy transferred on the hydroxy camptothecin, strengthen the fluorescence intensity of hydroxy camptothecin, make it have the fluorescent in situ expression characterization with the cancerous cell effect.
2. a kind of chitosan of the present invention props up and carries hydroxy camptothecin-quantum dot FRET combined probe; But the specificity binding characteristic targeting through folic acid and folacin receptor is delivered to the tumor cancerous cell and it is dyeed, according to fluorescence behavior observation combined probe in tumor cancerous cell each regional mechanism and regularity of distribution; Hydroxy camptothecin discharge and with tumor cancerous cell mechanism in; The FRET composite construction of combined probe changes; The fluoroscopic image of quantum dot recovers gradually; Through the real-time monitoring of information such as quantum dot fluorescence Strength Changes size and rate of change, can realize the original position real-time dynamic monitoring of hydroxy camptothecin and tumor cancerous cell mechanism indirectly.
Description of drawings
Fig. 1 is the structural representation of composite fluorescence probe system of the present invention.
1, chitosan 2, quantum dot 3, folic acid 4, hydroxy camptothecin 5, folacin receptor
6, tumor cancerous cell 7, drug release process 8, nucleus
The specific embodiment
In conjunction with accompanying drawing a kind of chitosan of the present invention being propped up the composition and the mechanism of carrying hydroxy camptothecin-quantum dot FRET combined probe explains.
A kind of chitosan of the present invention props up and carries hydroxy camptothecin-quantum dot FRET combined probe, and this combined probe includes modified with folic acid chitosan, quantum dot and anticarcinogen hydroxy camptothecin; Said quantum dot is for having certain wavelength, and can be coupled with the anticarcinogen hydroxy camptothecin, forms to have the combined probe structure of FRET (FRET) characteristic, and under ultraviolet light or excited by visible light, can express one type of quantum dot of FRET characteristic.Said combined probe is under ultraviolet light or excited by visible light, and quantum dot and hydroxy camptothecin generation photoelectricity shift, quantum dot generation fluorescent quenching, and excited energy transferred on the hydroxy camptothecin, express the FRET characteristic, the hydroxy camptothecin fluorescence intensity strengthens.Said chitosan is an amphipathic chitose, and its molecular weight is 2000 ~ 4000.In the said FRET combined probe structure, quantum dot is an energy donor, and hydroxy camptothecin is an energy acceptor.The emission wavelength of quantum dot is 353 ~ 373nm.
As shown in Figure 1, a kind of chitosan involved in the present invention props up a year hydroxy camptothecin-quantum dot FRET combined probe function and is achieved in that
A kind of chitosan involved in the present invention props up and carries hydroxy camptothecin-quantum dot FRET combined probe, and the chitosan 1 that this probe has anticarcinogen hydroxy camptothecin 4, quantum dot 2 and folic acid 3 to modify constitutes.Selected anticarcinogen hydroxy camptothecin 4 is that a kind of anticancer spectrum is wider, and the antineoplastic agent that toxicity is little itself has certain fluorescent characteristic, and its excitation wavelength is 363nm, and emission wavelength is 550nm; Selected quantum dot 2 is a water-soluble quantum dot, has certain wavelength, and can have FRET FRET composite construction as energy donor and hydroxy camptothecin 4 formation, and under ultraviolet light or excited by visible light, can express the FRET characteristic; The chitosan 1 that selected folic acid 3 is modified is an amphipathic chitose, and its molecular weight size is 2000 ~ 4000; Quantum dot 2 is assembled in folic acid 3 beautify chitosans 1 through the parcel mode and constitutes modified with folic acid chitosan-quantum dot complex, and hydroxy camptothecin 4 also is assembled in modified with folic acid chitosan-quantum dot complex through the parcel mode.To have the quantum dot 2 and 4 couplings of anticarcinogen hydroxy camptothecin of certain wavelength, the emission wavelength of quantum dot 2 and the excitation wavelength of hydroxy camptothecin 4 are complementary, formation has FRET FRET composite construction.Under ultraviolet light or excited by visible light, quantum dot 2 with hydroxy camptothecin 2 photoelectricity takes place to be shifted, and fluorescent quenching takes place quantum dot 2, and excited energy is transferred on the hydroxy camptothecin 4, expresses the FRET characteristic, and hydroxy camptothecin 4 fluorescence intensities strengthen.This probe carrier is chosen as chitosan 1, and chitosan is amphipathic and modifies with folic acid 3.Utilize the specificity binding characteristic of folic acid 3 and folacin receptor 5 to realize of the targeting delivery effect of this probe to tumor cancerous cell 6; Utilize the FRET characteristic of this combined probe; Through in probe and the carninomatosis kitchen range interaction process; The monitoring of FRET phenomenon structure and quantum dot 2 fluoroscopic image change informations, the original position real-time dynamic monitoring of the interaction process of realization combined probe and tumor cancerous cell 6.
After chitosan props up carried anticancer medicine hydroxy camptothecin-quantum dot FRET combined probe entering biological tissue; Specificity binding characteristic targeting through folic acid 3 and folacin receptor 5 is transported on tumor cancerous cell 6 cell membrane; Chitosan 1 itself with positive charge and tumor cancerous cell 6 cell membrane on negative charge combine; Form endosome, and get into tumor cancerous cell 6 cytoplasms through the endocytosis of cell.The proton pump that the ATP enzyme drives gets into endosome with the proton transhipment, makes the endosome surface be acid, and pH value is about 5, chitosan 1 dissolving, and anticarcinogen hydroxy camptothecin 4 obtains discharging, and acts on nucleus 8 and the performance drug effect.In this course, the FRET of combined probe dyes to tumor cancerous cell 5, changes clear condition through its combined probe fluorescence behavior variation and quantum dot fluorescence, can observe combined probe in tumor cancerous cell 5 each regional mechanism and regularities of distribution.
In drug release process 7; Because the fluorescent probe with FRET characteristic has high susceptibility for the spatial orientation of distance and fluorophor; FRET between hydroxy camptothecin 4 and the quantum dot 2 is damaged; Its fluorescence behavior changes; The fluoroscopic image of quantum dot 2 recovers and changes in time, through the real-time monitoring of information such as and rate of change big or small to the variation of quantum dot fluorescence intensity in this process, can realize the original position real-time dynamic monitoring of tumor cancerous cell 6 and hydroxy camptothecin 4 mechanisms indirectly.
Embodiment
1) with hydrophilic succinic acid and hydrophobicity long-chain anhydride beautify chitosan, that it is had is hydrophobic-and hydrophilic amphipathic.To its further modification, and itself and water-soluble quantum dot carboxyl CdTe be assembled into modified with folic acid chitosan-quantum dot complex with folic acid.With the complex is carrier, and assembling cancer therapy drug hydroxy camptothecin forms hydroxy camptothecin-carboxyl CdTe quantum dot FRET fluorescent probe system.This probe is used for labelling treatment pulmonary carcinoma A459 cell to be found; Probe optionally labelling gets into lung carcinoma cell; In hydroxy camptothecin and lung carcinoma cell mechanism, fluoroscopic image is clear, along with the release of hydroxy camptothecin; The fluoroscopic image of quantum dot recovers gradually, and its fluorescence intensity returns to 1.0 from 0.2 gradually.According to the recovery situation of quantum dot fluorescence intensity, followed the tracks of the mechanism of hydroxy camptothecin and lung carcinoma cell well, realized the original position real-time dynamic monitoring of curative effect of medication.
Claims (3)
1. a chitosan props up and carries hydroxy camptothecin-quantum dot FRET combined probe, and it is characterized in that: this combined probe includes chitosan, quantum dot and the anticarcinogen hydroxy camptothecin of modified with folic acid;
Said quantum dot is for having certain wavelength; Can be coupled as energy donor and anticarcinogen hydroxy camptothecin; Formation has the combined probe structure of FRET (FRET) characteristic; Under ultraviolet light or excited by visible light, can shift with anticarcinogen hydroxy camptothecin generation photoelectricity and fluorescent quenching takes place, and excited energy is transferred on the anticarcinogen hydroxy camptothecin and one type of water-soluble quantum dot of expressing the FRET characteristic.
2. prop up according to the said chitosan of claim 1 and carry hydroxy camptothecin-quantum dot FRET combined probe, it is characterized in that: said chitosan is an amphipathic chitose, and its molecular weight size is 2000 ~ 4000.
3. prop up according to the said chitosan of claim 1 and carry hydroxy camptothecin-quantum dot FRET combined probe, it is characterized in that: in the said FRET combined probe structure, water-soluble quantum dot is an energy donor, and its emission wavelength is 353 ~ 373nm.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012102166407A CN102698294A (en) | 2012-06-28 | 2012-06-28 | Chitosan-supported hydroxycamptothecine-quantum dot FRET (Fluorescence Resonance Energy Transfer) composite probe |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012102166407A CN102698294A (en) | 2012-06-28 | 2012-06-28 | Chitosan-supported hydroxycamptothecine-quantum dot FRET (Fluorescence Resonance Energy Transfer) composite probe |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102698294A true CN102698294A (en) | 2012-10-03 |
Family
ID=46891530
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2012102166407A Pending CN102698294A (en) | 2012-06-28 | 2012-06-28 | Chitosan-supported hydroxycamptothecine-quantum dot FRET (Fluorescence Resonance Energy Transfer) composite probe |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102698294A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103656668A (en) * | 2013-12-06 | 2014-03-26 | 山东省医学科学院药物研究所 | Bortezomib sustained-release preparation and preparation method thereof |
| CN110740750A (en) * | 2017-03-15 | 2020-01-31 | 纳米技术有限公司 | Photo-responsive quantum dot drug delivery system |
-
2012
- 2012-06-28 CN CN2012102166407A patent/CN102698294A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103656668A (en) * | 2013-12-06 | 2014-03-26 | 山东省医学科学院药物研究所 | Bortezomib sustained-release preparation and preparation method thereof |
| CN103656668B (en) * | 2013-12-06 | 2016-08-17 | 山东省医学科学院药物研究所 | Bortezomib slow releasing preparation and preparation method thereof |
| CN110740750A (en) * | 2017-03-15 | 2020-01-31 | 纳米技术有限公司 | Photo-responsive quantum dot drug delivery system |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Li et al. | Temporal multiplexed in vivo upconversion imaging | |
| Qi et al. | Aggregation-induced emission luminogen with near-infrared-II excitation and near-infrared-I emission for ultradeep intravital two-photon microscopy | |
| Dong et al. | Lanthanide nanoparticles: from design toward bioimaging and therapy | |
| Jiang et al. | Optical imaging-guided cancer therapy with fluorescent nanoparticles | |
| Tang et al. | Near-infrared excited orthogonal emissive upconversion nanoparticles for imaging-guided on-demand therapy | |
| Mahata et al. | Near-infrared-triggered upconverting nanoparticles for biomedicine applications | |
| Meng et al. | Fabricating Aptamer‐Conjugated PEGylated‐MoS2/Cu1. 8S Theranostic Nanoplatform for Multiplexed Imaging Diagnosis and Chemo‐Photothermal Therapy of Cancer | |
| Yao et al. | Upconversion luminescence nanomaterials: A versatile platform for imaging, sensing, and therapy | |
| Park et al. | Theranostic probe based on lanthanide‐doped nanoparticles for simultaneous in vivo dual‐modal imaging and photodynamic therapy | |
| Li et al. | Advances in the application of upconversion nanoparticles for detecting and treating cancers | |
| Biffi et al. | Applications of nanoparticles in cancer medicine and beyond: optical and multimodal in vivo imaging, tissue targeting and drug delivery | |
| Feng et al. | Upconversion‐nanophosphor‐based functional nanocomposites | |
| Qu et al. | Near-IR emissive rare-earth nanoparticles for guided surgery | |
| Zhang et al. | Sub-10 nm water-dispersible β-NaGdF4: X% Eu3+ nanoparticles with enhanced biocompatibility for in vivo x-ray luminescence computed tomography | |
| Irimie et al. | Future trends and emerging issues for nanodelivery systems in oral and oropharyngeal cancer | |
| Zheng et al. | Near-infrared light-excited upconverting persistent nanophosphors in vivo for imaging-guided cell therapy | |
| Song et al. | Sensitizing the luminescence of lanthanide-doped nanoparticles over 1500 nm for high-contrast and deep imaging of brain injury | |
| Ding et al. | X-ray-activated simultaneous near-infrared and short-wave infrared persistent luminescence imaging for long-term tracking of drug delivery | |
| Sekiyama et al. | Delayed increase in near-infrared fluorescence in cultured murine cancer cells labeled with oxygen-doped single-walled carbon nanotubes | |
| Chai et al. | Influence on the apparent luminescent lifetime of rare-earth upconversion nanoparticles by quenching the sensitizer’s excited state for hypochlorous acid detection and bioimaging | |
| Muthu et al. | Upconversion nanotheranostics: emerging designs for integration of diagnosis and therapy | |
| Han et al. | Hybrid mesoporous MnO2-upconversion nanoparticles for image-guided lung cancer spinal metastasis therapy | |
| Park | Polysaccharide-based near-infrared fluorescence nanoprobes for cancer diagnosis | |
| Li et al. | Near-infrared-II ratiometric fluorescence probes for non-invasive detection and precise navigation surgery of metastatic sentinel lymph nodes | |
| Zhou et al. | A “protective umbrella” nanoplatform for loading ICG and multi-modal imaging-guided phototherapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20121003 |