CN112451663A - Nano complex for fluorescence imaging navigation tumor resection and photothermal therapy and preparation method thereof - Google Patents
Nano complex for fluorescence imaging navigation tumor resection and photothermal therapy and preparation method thereof Download PDFInfo
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- CN112451663A CN112451663A CN202011326790.4A CN202011326790A CN112451663A CN 112451663 A CN112451663 A CN 112451663A CN 202011326790 A CN202011326790 A CN 202011326790A CN 112451663 A CN112451663 A CN 112451663A
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Abstract
The invention relates to the technical field of biomedical materials, in particular to the technical field of tumor molecular image diagnosis and treatment probe molecules, and particularly relates to a nano complex for fluorescence imaging navigation tumor resection and photothermal treatment and a preparation method thereof, wherein the prepared nano probe can load near infrared dye IR820, and quantum dots do not emit light under the competitive absorption action in normal tissues; in tumor cells, the tetrasulfide bond in the virus organic silicon shell layer can be degraded by glutathione in a tumor microenvironment to trigger release of loaded IR820, so that the quantum dots can emit 1650nm fluorescence for efficient and specific NIR IIb fluorescence imaging-guided tumor surgical resection, and the surgical thoroughness is improved. In addition, IR820 can also be used for NIR IIb fluorescence imaging-guided photothermal therapy of distal metastases, increasing the thoroughness of the treatment and improving the long-term survival of patients.
Description
Technical Field
The invention relates to the technical field of biomedical materials, in particular to the technical field of tumor molecular imaging diagnosis and treatment probe molecules, and particularly relates to a nano complex for fluorescence imaging navigation tumor resection and photothermal treatment and a preparation method thereof.
Background
In clinical diagnosis and treatment, compared with the existing clinical medical image examination mode, molecular fluorescence imaging has the advantages of low cost, simplicity, feasibility, safety, real-time performance, high resolution and strong specificity. Therefore, there is an urgent need to develop a new fluorescence imaging guided tumor resection strategy, which can realize non-invasive, high-penetration, high-resolution, high-sensitivity and low-noise real-time imaging of tumor lesions in the operation with the help of a corresponding fluorescence probe, and guide surgeons to perform precise positioning and complete surgical resection of the tumor lesions in the operation. In recent years, the newly developed Near-infrared two-zone (NIR II, 900-plus 1700nm) fluorescence, especially the Near-infrared two-zone b (NIR IIb, 1500-plus 1700nm) fluorescence, greatly overcomes the limitations of low tissue penetration depth and low signal-to-noise ratio when the Near-infrared one-zone (NIR I, 650-plus 900nm) fluorescence is used for detecting deep tumors; thus, probes emitting in the NIR IIb region are ideal contrast agents for fluorescence imaging guided surgical resection. Therefore, the NIR IIb fluorescent probe with high sensitivity, high resolution and high penetration depth of the tumor is developed, the fluorescence imaging guided surgical resection is carried out, and the NIR IIb fluorescent probe has important significance for improving the survival rate of patients and reducing the recurrence rate of the tumor.
However, since tumors often show diffuse invasive growth, tumor tissue and normal tissue often lack distinct boundaries, the specificity of NIR IIb fluorescent probes for tumor imaging remains to be improved. With the continuous progress of tumor biology research, it is gradually recognized that: tumors are abnormal tissues with very complex structures and unique microenvironments. There are many differences between the tumor microenvironment and the normal tissue microenvironment, such as weak acidity, enzyme overexpression, high reducibility, and oxygen deficiency. Therefore, the NIR IIb intelligent nanoprobe with the tumor microenvironment stimulus response is designed, the specificity of the NIR IIb intelligent nanoprobe at the tumor part can be improved, and the NIR IIb intelligent nanoprobe is beneficial to accurate positioning of the tumor before operation. When most tumors are found, there is already a potential spread of cancer cells, and even some surgically completely resected tumors still do not avoid metastasis and recurrence. The Photothermal Therapy (PTT) has the advantages of small wound, high selectivity of an illumination area, killing effect on different types of tumor cells and the like. Therefore, the combination of surgical resection and photothermal therapy can further increase the thoroughness of tumor treatment, and is expected to become a new means and method for radically treating tumors.
Disclosure of Invention
The invention aims to provide a nano complex for fluorescence imaging navigation tumor resection and photothermal therapy and a preparation method thereof, so as to realize specific near-infrared two-region b fluorescence imaging of a tumor region, further guide surgical resection of in-situ tumors and photothermal therapy of metastasis, increase the thoroughness of tumor therapy and improve the long-term curative effect of tumors.
In order to achieve the technical purpose and achieve the technical effect, the invention discloses a nano complex for fluorescence imaging navigation tumor resection and photothermal therapy, wherein the nano complex is QD @ SiO2IR-TP in which QD is a quantum dot core with an average quantum yield greater than 20%, SiO2the-IR is an organic silicon layered structure loaded with near infrared dye IR, the TP is a targeting protein with tumor targeting effect, and the physical or chemical modification method and the SiO are adopted2IR recombination to form the above nanocomposite.
Wherein, the nano complex has a strong fluorescence emission signal at 1650nm, and is positioned between a lower absorption peak of water molecules and an optimum deep tissue optical imaging peak.
Preferably, the organosilicon layered structure is one of virus silicon, mesoporous silicon and dopamine-doped silicon spheres.
Preferably, the targeting protein is one of transmembrane peptide, RGD peptide, folic acid and follicle stimulating hormone receptor.
The invention also discloses a preparation method of the nano complex for fluorescence imaging navigation tumor resection and photothermal therapy, which comprises the following steps:
step 1: synthesizing a QD quantum dot core;
step 2: uniformly coating an organic silicon layered structure on the outer layer of the QD quantum dot core, and forming a mesoporous hole and/or a cavity for containing near infrared dye IR by an etching method;
and step 3: and compounding the target protein TP on the organic silicon layer by adopting a physical or chemical modification method to form a nano complex.
Preferably, the step 1 is to synthesize the PbS @ CdS quantum dots by a high-temperature solvothermal method.
Preferably, the step 2 specifically comprises the steps of wrapping amorphous silicon on the surface of PbS @ CdS quantum dots serving as a core by a reverse microemulsion method, and wrapping virus mesoporous inorganic silicon by a two-phase method; and finally obtaining the hollow viral mesoporous organic silicon-coated quantum dots after etching the amorphous silicon to form a cavity, wherein the cavity is used for loading the near-infrared dye IR 820.
Preferably, step 3 is specifically to chemically modify amino groups on the shell layer of the nanocarrier obtained in step 2, and to condense amino groups with carboxyl groups to form transmembrane peptides.
The invention has the following beneficial effects:
one of the advantages of the present invention is the construction of high quantum yield NIR IIb fluorescent probes for fluorescence imaging guided surgical resection: the NIR IIb fluorescent probe with high quantum yield has extremely high penetrability and signal-to-noise ratio, can accurately detect and efficiently remove deep tumors with high sensitivity, and prevents in-situ recurrence of the tumors.
The invention has the advantages of low toxicity of the NIR IIb composite probe, tumor cell adhesion: the hollow virus mesoporous organic silicon is wrapped to reduce the toxicity of quantum dots in the NIR IIb composite probe, and the rough virus-like surface can further increase the adhesion of tumor cells.
The invention has the third advantage that the NIR IIb composite probe with tumor microenvironment response is used for the operation excision guided by fluorescence imaging: the hollow virus mesoporous organic silicon shell layer of the composite probe can be degraded in response to GSH of a tumor microenvironment to release near infrared dye IR820 with competitive absorption, and quantum dots in the NIR IIb composite probe can emit 1650nm fluorescence for guiding surgical excision of primary tumors through fluorescence imaging; the released IR820 can carry out photothermal therapy on the metastasis, thoroughly inhibit tumor recurrence and tumor metastasis in two aspects, and greatly improve the survival time of patients.
Drawings
FIG. 1 is a schematic diagram of the progressive construction of a near-infrared two-b-region fluorescent composite probe.
FIG. 2 is a schematic diagram of a transmission electron micrograph (A-C) of PbS @ CdS, PbS @ CdS @ Silica, QD @ HVMO and a particle size distribution (D-E) of the three in dynamic light scattering measurement, with an inset diagram corresponding to the transmission electron micrograph and a scale of 40 nm.
FIG. 3(A) emission spectra of PbS @ CdS, PbS @ CdS @ Silica, QD @ HVMO at 808nm excitation; (B) the emission spectrum of QD @ HVMO and the transmittance spectrum of water molecules.
FIG. 4 change in intensity of light emitted at 1650nm after continuous exposure of QD @ HVMO dispersed in water, PBS, blood, and culture medium to 808nm laser light for various periods of time; (B) QD @ HVMO emitted light at 1650nm with a change in intensity after incubation in water, PBS, blood, media for various times.
FIG. 5 shows near-infrared bib zone fluorescence imaging images of the composite probe at different hours after the tail vein injection and H & E staining images of the tumor after the resection by near-infrared bib zone fluorescence imaging navigation operation 12 hours after the injection.
Fig. 6 composite nanoprobe for hyperthermia of epidermoid tumors. (A) Changes in tumor size; (B) h & E and TUNNEL staining of tumor sites after 4 days of treatment in different treatment groups.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments.
Example 1
As shown in FIG. 1, the invention discloses a method for explaining PbS @ CdS quantum dots and virus organic mesoporous silicon by taking as an example, which comprises the following steps:
the PbS @ CdS quantum dots are thermally synthesized by a high-temperature solvent, and the influence of factors such as different core-shell size ratios on the emission waveband and the emission intensity of the quantum dots under the excitation of 808nm is examined.
Wrapping amorphous silicon on the surface of PbS @ CdS quantum dots serving as cores by a reverse microemulsion method, and wrapping virus mesoporous inorganic silicon by a two-phase method; and after the amorphous silicon is etched to form a cavity, finally obtaining the hollow NIR IIb quantum dots (QD @ HVMO) wrapped by the virus mesoporous organic silicon. The cavity of the shell is used for loading the near infrared dye IR820, and amino groups are modified at the outermost layer of the shell to graft the targeting polypeptide.
Loading IR820 on an internal cavity of the QD @ HVMO to construct the QD @ HVMO-IR 820; QD @ HVMO-IR820-CPP is synthesized by grafting transmembrane peptide through amino-carboxyl condensation, so that targeted phagocytosis of cancer cells is facilitated.
The specific synthesis method comprises the following steps:
PbS quantum dots were first synthesized by solvothermal (oleylamine system): the sulfur precursor is mainly prepared by 0.08g of sulfur powder and 7.5mL of oleylamine, keeping the mixture at 160 ℃ for 30min under the protection of argon gas at 120 ℃, and adding 10mL of ice-cold cyclohexane and 20mL of ethanol to stop the reaction. After three washes by cyclohexane centrifugation, it was dispersed in octadecene. PbS @ CdS quantum dots: 1.2g of CdO, 8mL of oleic acid and 20mL of octadecene are heated to 200 ℃ under the argon atmosphere, and then cooled to 100 ℃ to prepare a Cd precursor. 5mL of the PbS synthesized as described above dispersed in octadecene was bubbled for 10min under argon, and then added to the Cd precursor. After 30min at 100 ℃ 5mL of ice-cold cyclohexane were added. And finally, the PbS @ CdS quantum dots are dispersed in cyclohexane after being centrifugally washed for three times by ethanol.
Wrapping solid silicon and virus mesoporous organic silicon: the solid silicon ball is wrapped by a reverse microemulsion method, the silicon source adopts tetraethyl orthosilicate TEOS), the virus mesoporous organic silicon adopts TEOS and bis- [3- (triethoxysilyl) propyl ] -tetrasulfide (BTES) as the silicon source (the proportion is 5:4), and the two-phase method is adopted for wrapping.
Etching the solid silicon ball and modifying amino groups on the surface of the nano composite probe: the solid silicon ball is removed by 0.1M Na2CO3And etching for 10 hours at 50 ℃ under stirring. Modifying the surface amino group of the hollow virus mesoporous organic silicon material (PbS @ CdS @ Gd @ HVMO), and refluxing for 24h at 37 ℃ by adopting a silane coupling Agent (APTES) in an ethanol system to obtain the composite probe (QD @ HVMO) with the hollow virus mesoporous organic silicon coated quantum dots, wherein the particle size of the composite probe is about 30nm, and is shown in figure 2.
Example 2
In order to further characterize the fluorescence spectrum and fluorescence stability of the obtained composite probe, the emission spectrum of PbS @ CdS, PbS @ CdS @ Silica, QD @ HVMO obtained in example 1 under the excitation of 808nm was measured in this example.
As shown in FIG. 3, it can be seen from the emission spectrum that PbS @ CdS has strong emission (1650nm) in NIR IIb, and the emission intensity is not reduced obviously after solid silicon and hollow virus mesoporous organosilicon are coated. And meanwhile, the emission at the position can avoid the maximum absorption peak of water, so that the method can be used for efficient NIR IIb fluorescence imaging.
As shown in FIG. 4, the fluorescence stability of the quantum dots coated with the mesoporous organosilicon of the hollow virus is measured, and it can be seen from the results that under the continuous irradiation of the 808nm laser, the emitted light of the composite nano-probe can be kept stable in water, PBS, blood and culture medium, and has strong photobleaching resistance. Meanwhile, the fluorescence intensity can not be changed after the culture medium is stored in water, PBS, blood and culture medium for 96 hours.
Example 3
To further characterize the fluorescence imaging effect of the obtained composite probe in the organism, in situ tumor mouse fluorescence imaging characterization was performed with QD @ HVMO-IR820-CPP obtained in example 1.
NIR IIb fluorescence imaging: 10 in situ tumor mice were divided into 2 groups (5 mice per group), QD @ HVMO-IR820-CPP was injected into the tail vein, and then the NIR IIb fluorescence images of the whole body of the mice were taken by InGaAs CCD at different time periods (2h,4h,6h,8h,12h,18h,24h,48h), 1500nm filter and 808nm laser irradiation. The change in signal intensity and signal to noise ratio at the tumors at different time points were obtained, and as shown in fig. 5, the experimental results showed that the tumors were brightest 12 hours after injection.
NIR IIb fluorescence imaging guided surgical resection: in the orthotopic tumor and popliteal lymph node model, the surgical resection of the liver orthotopic tumor is carried out by using NIR IIb fluorescence imaging guidance within the maximum time point of the tumor; after the excised tumor is fixed for 24 hours by formaldehyde (10%), the excised tumor is sequentially subjected to alcohol gradient dehydration, xylene transparence and paraffin embedding to prepare a section, H & E staining, the histopathological structure is observed to carry out pathological section, whether the tumor tissue is excised completely is determined, and as shown in figure 5, the tumor and the normal tissue have obvious boundaries to prove that the tumor is excised completely.
Example 4
To further characterize the growth inhibitory effect of the obtained nanocomplexes on biological tumors, this example performed a different set of photothermal treatments on mouse epidermomas with the materials obtained in example 1.
10 tumor-bearing mice are divided into 2 groups (5 mice in each group), a QD @ HVMO group, a QD @ HVMO-IR820-CPP group, a QD @ HVMO-IR820 group, an IR820 group, a PBS group and a laser irradiation group are injected into the tail vein, NIR IIb fluorescence imaging is carried out on popliteal lymph nodes, the maximum enrichment time point of the tumor is detected, the size change of the measured tumor is respectively detected through 808nm laser irradiation in the time point, H & E and TUNNEL staining is carried out on the tumor after 5 days of treatment, and the result is shown in figure 6.
The above description is only for the preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any changes or substitutions that can be easily conceived by those skilled in the art within the technical scope of the present invention are included in the scope of the present invention.
Claims (8)
1. A nano complex for fluorescence imaging navigation tumor resection and photothermal therapy is characterized in that the nano complex is QD @ SiO2IR-TP in which QD is a quantum dot core with an average quantum yield greater than 20%, SiO2the-IR is an organic silicon layered structure loaded with near infrared dye IR, the TP is a targeting protein with tumor targeting effect, and the physical or chemical modification method and the SiO are adopted2IR recombination to form the above nanocomposite.
2. The nanocomplex for fluorescence imaging navigation tumor resection and photothermal therapy according to claim 1, wherein: the nano complex has a strong fluorescence emission signal at 1650nm, and is positioned between a lower absorption peak of water molecules and an optimum deep tissue optical imaging peak.
3. The nanocomplex for fluorescence imaging navigation tumor resection and photothermal therapy according to claim 2, wherein: the organic silicon layered structure is one of virus silicon, mesoporous silicon and dopamine-doped silicon spheres.
4. The nanocomplex for fluorescence imaging navigation tumor resection and photothermal therapy according to claim 3, wherein: the target protein is one of transmembrane peptide, RGD peptide, folic acid and follicle stimulating hormone receptor.
5. A method for preparing a nanocomplex for fluorescence imaging navigation tumor resection and photothermal therapy, wherein the nanocomplex is any one of claims 1 to 4, and the method comprises the following steps:
step 1: synthesizing a QD quantum dot core;
step 2: uniformly coating an organic silicon layered structure on the outer layer of the QD quantum dot core, and forming a mesoporous hole and/or a cavity for containing near infrared dye IR by an etching method;
and step 3: and compounding the target protein TP on the organic silicon layer by adopting a physical or chemical modification method to form a nano complex.
6. The method for preparing the nanocomposite for fluorescence imaging navigation tumor resection and photothermal therapy according to claim 5, wherein the step 1 is to synthesize the PbS @ CdS quantum dots by a high temperature solvothermal method.
7. The method for preparing the nanocomposite for fluorescence imaging navigation tumor resection and photothermal therapy according to claim 6, wherein the step 2 comprises coating amorphous silicon on the surface of PbS @ CdS quantum dots as a core by a reverse microemulsion method, and then coating virus mesoporous inorganic silicon by a two-phase method; and finally obtaining the hollow viral mesoporous organic silicon-coated quantum dots after etching the amorphous silicon to form a cavity, wherein the cavity is used for loading the near-infrared dye IR 820.
8. The method for preparing the nanocomplex for fluorescence imaging navigation tumor resection and photothermal therapy according to claim 7, wherein the step 3 is to chemically modify amino group on the shell layer of the nanocarrier obtained in the step 2, and the transmembrane peptide is formed by condensing amino group and carboxyl group.
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Cited By (1)
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---|---|---|---|---|
CN113927027A (en) * | 2021-09-16 | 2022-01-14 | 福建医科大学孟超肝胆医院(福州市传染病医院) | Near-infrared region-excited rare earth nanocrystal loaded with viroid hollow manganese oxide and preparation method and application thereof |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105056233A (en) * | 2015-08-12 | 2015-11-18 | 苏州大学 | Multifunctional mesoporous silica nanoparticles having near-infrared photothermal and in-vivo fluorescence imaging characteristics as well as preparation method and application of mesoporous silica nanoparticles |
-
2020
- 2020-11-24 CN CN202011326790.4A patent/CN112451663A/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105056233A (en) * | 2015-08-12 | 2015-11-18 | 苏州大学 | Multifunctional mesoporous silica nanoparticles having near-infrared photothermal and in-vivo fluorescence imaging characteristics as well as preparation method and application of mesoporous silica nanoparticles |
Non-Patent Citations (5)
Title |
---|
LI T等: "Irinotecan/IR-820 coloaded nanocomposite as a cooperative nanoplatform for combinational therapy of tumor", 《NANOMEDICINE》 * |
XIA H X等: "Folic acid-conjugated silica-coated gold nanorods and quantum dots for dual-modality CT and fluorescence imaging and photothermal therapy", 《JOURNAL OF MATERIALS CHEMISTRY B》 * |
ZEBIBULA A等: "Ultrastable and biocompatible NIR‐II quantum dots for functional bioimaging", 《ADVANCED FUNCTIONAL MATERIALS》 * |
彭司勋等: "《中国药学年鉴 2015 第31卷》", 31 August 2016 * |
金征宇等: "《基因与纳米探针-医学分子成像理论与实践 下》", 30 November 2017 * |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113927027A (en) * | 2021-09-16 | 2022-01-14 | 福建医科大学孟超肝胆医院(福州市传染病医院) | Near-infrared region-excited rare earth nanocrystal loaded with viroid hollow manganese oxide and preparation method and application thereof |
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