A homologous targeting NIR-II fluorescent imaging nano platform, a preparation method thereof and application thereof in tumor imaging
By coating cancer cell membranes onto the surface of CsLu(1-xy)YbxEryFz nanoparticles, a homologous targeting NIR-II region fluorescence imaging nanoplatform is formed, which solves the problems of low imaging resolution and targeting efficiency in existing technologies, and realizes high-resolution tumor imaging and precise resection.
Patent Information
- Application Number
- CN202410808344.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2024-06-21
- Publication Date
- 2025-12-26
- Estimated Expiration
- 2044-06-21
AI Technical Summary
Existing NIR-I region fluorescence imaging technology is affected by light scattering, light absorption and biological tissue autofluorescence, resulting in low imaging spatial resolution, signal-to-background ratio and limited penetration depth. Traditional NIR-II region fluorescence probes have problems such as emission bandwidth, photobleaching and heavy metal toxicity, resulting in low targeting efficiency.
Using CsLu(1-xy)YbxEryFz nanoparticles as luminescent centers, and after water-soluble treatment, they are coated onto cancer cell membranes to form a homologous targeting NIR-II region fluorescence imaging nanoplatform. Tumor imaging is then performed by utilizing the immune escape and tumor targeting properties of the cancer cell membrane.
It achieves high-resolution NIR-II region fluorescence imaging, with longer luminescence lifetime and photostability, improving tumor targeting efficiency and biocompatibility, and enabling precise guidance of tumor resection.
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Figure CN118903477B_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the technical field of NIR-II region fluorescence imaging, and particularly relates to a NIR-II fluorescence imaging probe and a preparation method and application thereof. BACKGROUND
[0002] Specific imaging diagnosis is of great significance for early detection of tumors and research on tumor metastasis. Among various imaging methods, fluorescence imaging is one of the most powerful imaging techniques in biological research and clinical application. However, NIR-I region fluorescence imaging is interfered by light scattering, light absorption and biological tissue autofluorescence, resulting in low imaging spatial resolution, signal background ratio (SBR) and limited penetration depth. In order to overcome the limitations of NIR-I region fluorescence imaging, through optical simulation prediction, it is found that the near-infrared two region window (NIR-II, 1000-1700 nm) is more conducive to fluorescence imaging. In addition to the further reduction of scattering coefficient at a fixed tissue depth, the NIR-II region tissue autofluorescence decreases exponentially, and is almost zero when the wavelength is greater than ≈1500 nm. Although the light absorption of various biological tissues in the NIR-II region is slightly higher than that in the NIR-I region, in the case of reduced scattering loss and almost zero autofluorescence, the NIR-II region fluorescence imaging has higher spatial resolution, signal-to-noise ratio and penetration depth. Therefore, NIR-II region fluorescence imaging is becoming a rapidly developing field
[0003] In recent years, researchers have developed various types of NIR-II region fluorescence imaging probes, such as carbon nanotubes (CNTs), organic fluorophores, semiconductor quantum dots (QDs) (such as PbSe and AgS), etc. However, carbon nanotubes usually exhibit a wide emission band (>300 nm) and low quantum yield (QY) (0.1-0.4%), which hinders their practical application. For organic fluorophores, light bleaching and poor stability limit their application. In addition, semiconductor quantum dots also have some unavoidable problems, such as light flicker or inherent toxicity of heavy metal elements (such as Pb and Cd). Therefore, it is urgent to find new NIR-II region fluorescence nanoprobes to overcome the inherent limitations of traditional nanoprobes.
[0004] The electronic configuration of trivalent lanthanide ions (Ln 3+ ) is 4f n 5s 2 5p 6 (n=1-13), due to the rich energy levels of Ln 3+ , its emission covers the visible and NIR regions. It is reported that some Ln 3+ ions (such as Yb 3+ , Tm 3+ , Er 3+ , Ho3+ , Dy 3 + , Sm 3+ , Nd 3+ and Pr 3+ ) can produce fluorescent emission in the NIR-II region, and the rare earth ion down-conversion luminescence has a large Stokes shift, a narrow emission half-width, and a great application potential in fluorescence imaging. Therefore, Yb 3+ , Er 3 + is introduced into the CsLu (1-x-y) Yb x Er y F z matrix to obtain high-intensity NIR-II region fluorescence, and then surgical navigation is carried out.
[0005] Nanoparticles are easily recognized and removed by the reticuloendothelial system or mononuclear phagocytes in the immune system after entering the blood. In addition, non-specific proteins and biological molecules can easily adhere to the surface of the nanoparticles, further interfering with the interaction between the nanoparticles and the biological system. In the process of fluorescence imaging, nanoparticles can usually achieve non-specific targeting under the enhanced permeability and retention (EPR) effect in vivo, but the targeting efficiency is low. Therefore, it is very important to further construct actively targeted nanoparticles after preparing nanomaterials. Cell membranes can endow nanoparticles with unique biological properties, and by fusing cell membranes to the surface of drug nanoparticles, nanoparticles can have the properties of the original cell membrane and improve the stability of nanoparticles. Among different types of cell membranes, cancer cell membranes have the ability of immune escape and tumor active targeting, and coating cancer cell membranes on the surface of nanoparticles can endow them with active targeting ability. SUMMARY
[0006] This part aims to summarize some aspects of the embodiments of the present application and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this part and the abstract and title of the specification to avoid obscuring the purpose of this part, the abstract and the title, and such simplifications or omissions cannot be used to limit the scope of the present application.
[0007] In view of the above and / or problems existing in the prior art, the present application is proposed.
[0008] Therefore, the purpose of the present application is to overcome the deficiencies in the prior art and provide a homologous targeting NIR-II region fluorescence imaging nano-platform.
[0009] To solve the above technical problems, the present application provides the following technical solutions: comprising,
[0010] CsLu (1-x-y) Ybx Er y F z The nanoparticles are light emitting centers, and after water-soluble treatment, the cancer cell membranes are coated on the surface of the nanoparticles by extrusion to form a homologous targeting NIR-II region fluorescent imaging nano platform;
[0011] The CsLu (1-x-y) Yb x Er y F z The value of x in the nanoparticles is 0-0.98, the value of y is 0.02-0.98, and the value of z is 4-7.
[0012] As a preferred scheme of the homologous targeting NIR-II region fluorescent imaging nano platform, the cancer cell membrane is combined with the CsLu (1-x-y) Yb x Er y F z The mass ratio of the nanoparticles is 0.5-2:1.
[0013] As a preferred scheme of the homologous targeting NIR-II region fluorescent imaging nano platform, the cancer cell membrane includes mouse breast cancer cell membrane and mouse colon cancer cell membrane.
[0014] Another object of the present application is to provide a preparation method of the homologous targeting NIR-II region fluorescent imaging nano platform.
[0015] To solve the above technical problems, the present application provides the following technical scheme: comprising,
[0016] Lu salt, Yb salt, Er salt, Cs2CO3, oleic acid, oleylamine and octadecene are mixed and heated under vacuum conditions to form a transparent solution, and then cooled to room temperature under argon atmosphere, and then NH4F is added for synthesis reaction, and after the reaction is completed, washing is performed to obtain the CsLu (1-x-y) Yb x Er y F z The nanoparticles are the CsLu (1-x-y) Yb x Er y F z The value of x in the nanoparticles is 0-0.98, the value of y is 0.02-0.98, and the value of z is 4-7.
[0017] The CsLu (1-x-y) Yb x Er y F z The nanoparticles are dissolved in a non-polar or moderately polar solvent, and NH2-PEG 2000- DSPE, ultrasonic mixing, to obtain water-soluble CsLu (1-x-y) Yb x Er y F z nanoparticles
[0018] The extracted cancer cell membrane is mixed with CsLu (1-x-y) Yb x Er y F z nanoparticles in PBS, water bath ultrasonic, repeatedly extruded through the extruder, to obtain the homologous targeting NIR-II region fluorescent imaging nano platform.
[0019] As a preferred embodiment of the preparation method of the homologous targeting NIR-II region fluorescent imaging nano platform, the salt comprises Ac salt or Cl salt.
[0020] As a preferred embodiment of the preparation method of the homologous targeting NIR-II region fluorescent imaging nano platform, the molar ratio of Yb salt to Er salt is 9-19:1-5, and the molar ratio of Lu salt, Cs2CO3 and NH4F is 1-4:1-3:5-14.
[0021] As a preferred embodiment of the preparation method of the homologous targeting NIR-II region fluorescent imaging nano platform, when the amount of oleic acid is 6-15 mL, the amount of oleylamine is 0-4 mL, and the amount of octadecene is 10-15 mL.
[0022] As a preferred embodiment of the preparation method of the homologous targeting NIR-II region fluorescent imaging nano platform, the reaction temperature of the synthesis reaction is 285-315 DEG C, and the reaction time is 45-60 min.
[0023] As a preferred embodiment of the preparation method of the homologous targeting NIR-II region fluorescent imaging nano platform, the non-polar or moderately polar solvent comprises one of acetone, tetrahydrofuran and cyclohexane.
[0024] Another object of the present application is to provide an application of the homologous targeting NIR-II region fluorescent imaging nano platform in tumor imaging.
[0025] The present application has the following advantages:
[0026] The present application combines the NIR-II region luminescence performance of CsLu (1-x-y) Yb x Er y F z nanoparticles and the good immune escape and tumor targeting of cancer cell membrane, and designs the cancer cell membrane coated CsLu(1-x-y) Yb x Er y F z nanoparticles, NIR-II region fluorescence imaging of the tumor is carried out and the tumor is guided to be resected by surgery;
[0027] Compared with existing visible region and NIR-I region fluorescent materials, the present application has a NIR-II region fluorescence emission peak, which is beneficial to high-resolution near-infrared fluorescence imaging, so that the tumor tissue can be accurately guided to be resected;
[0028] Compared with organic materials, the present application has a longer luminescence lifetime, and has higher light stability and biocompatibility, and is not easy to be photobleached.
[0029] Compared with other targeting materials, such as hyaluronic acid (HA) and polypeptides, the cancer cell membrane of the present application has the immune escape ability and homologous binding ability specific to cancer cells, and has better coating effect and better water stability, so that it has better accumulation effect in tumor tissue. BRIEF DESCRIPTION OF DRAWINGS
[0030] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings needed in the embodiment description will be briefly introduced below. Obviously, the drawings in the following description are only some embodiments of the present application, and other drawings can be obtained by those skilled in the art without creative labor. Among them:
[0031] Figure 1 The flow chart for constructing the homologous targeting NIR-II region fluorescence imaging nano platform of Example 1 of the present application.
[0032] Figure 2 The transmission electron microscope (TEM) image of the CsLu (1-x-y) Yb x Er y F z nanoparticles obtained in Example 1 of the present application.
[0033] Figure 3 The fluorescence spectrum of the CsLu (1-x-y) Yb x Er y F z nanoparticles obtained in Example 1 of the present application.
[0034] Figure 4 The result graph of the homologous targeting NIR-II fluorescence imaging nano platform obtained in Example 1 of the present application for guiding surgical removal of tumor.
[0035] Figure 5 The CsLu(1-x-y) Yb x Er y F z Fluorescence spectrum of the nanoparticles.
[0036] Figure 6 CsLu obtained from Example 3 of the present application (1-x-y) Yb x Er y F z Fluorescence spectrum of the nanoparticles.
[0037] Figure 7 CsLu obtained from Example 4 of the present application (1-x-y) Yb x Er y F z Fluorescence spectrum of the nanoparticles.
[0038] Figure 8 CsLu obtained from Example 5 of the present application with different Yb(Ac)3 (1-x-y) Yb x Er y F z Fluorescence spectrum of the nanoparticles.
[0039] Figure 9 CsLu obtained from Example 5 of the present application with different Er(Ac)3 (1-x-y) Yb x Er y F z Fluorescence spectrum of the nanoparticles.
[0040] Figure 10 CsLu obtained from Example 6 of the present application with different ratios of Ln(Ac)3:Cs2CO3:NH4F (1-x-y) Yb x Er y F z Fluorescence spectrum of the nanoparticles.
[0041] Figure 11 CsLu obtained from Example 7 of the present application with different high-temperature holding temperatures (1-x-y) Yb x Er y F z Transmission electron microscopy (TEM) image of the nanoparticles. DETAILED DESCRIPTION
[0042] In order to make the above objectives, features and advantages of the present application more apparent, the specific embodiments of the present application will be described in detail below with reference to the embodiments of the present application.
[0043] In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present application. However, it will be apparent to one skilled in the art that the present application can be practiced without the specific details set forth in this description. In other instances, well-known methods have not been described in detail in order not to unnecessarily obscure aspects of the present application.
[0044] Second, the "one embodiment" or "an embodiment" appearing in the specification herein indicates that a specific feature, structure or characteristic can be included in at least one implementation of the present application. The "in one embodiment" appearing in different places in the specification herein does not all refer to the same embodiment, nor is it an embodiment that is independent of or mutually exclusive with other embodiments.
[0045] The raw materials used in the present application are commercially available in the art without special instructions.
[0046] Example 1
[0047] Reference Figure 1 The present application is a method for constructing a homologous targeting NIR-II region fluorescent imaging nano-platform, specifically:
[0048] 1) 0.02 mmol Er(Ac)3, 0.18 mmol Yb(Ac)3, 0.8 mmol Lu(Ac)3 and 0.25 mmol Cs2CO3 were added to a three-necked flask containing 6 mL of oleic acid, 2 mL of oleylamine and 6 mL of octadecene. The mixture was heated to 120°C under vacuum until a transparent solution was formed. Then it was kept at room temperature under argon atmosphere for 30 min. Subsequently, 3.5 mmol NH4F was added. The mixture was heated to 300°C under vacuum, and kept at room temperature under argon atmosphere for 45 min. Then excess ethanol was added. The mixture was centrifuged at 10000 rpm for 15 min. After removing the supernatant, it was washed with ethanol for 3 times to obtain the CsLu (1-x-y) Yb x Er y F z nanoparticles. The obtained nanoparticles have a uniform size and have a NIR-II region fluorescence of 1530 nm, Figure 2 is its TEM image, Figure 3 is its fluorescence spectrum.
[0049] 2) CsLu (1-x-y) Yb x Er y F z nanoparticles were dissolved in cyclohexane to obtain 10 mg / mL of CsLu (1-x-y) Yb x Er y F zsolution, mixed with 20 mg / mL of NH2-PEG 2000 -DSPE aqueous solution, centrifuged at 15000 rpm for 5 min, washed with ultrapure water, to obtain water-soluble CsLu (1-x-y) Yb x Er y F z nanoparticles.
[0050] 3) After 48 hours of incubation of mouse breast cancer cells (4T1) in cell culture bottles, the cells were separated from the bottle wall using a cell scraper, the cells were collected by centrifugation and washed with PBS, and the cells were re-collected by centrifugation. According to the method of the reagent instruction, the cell particles were suspended in a hypotonic lysis solution containing a membrane protein extraction reagent, and kept in an ice water bath for 10-15 min, the above-mentioned cells were broken by repeated freeze-thaw method, the broken material was collected by centrifugation (6000g, 10 min, 4℃), the supernatant was reserved, and finally the cell membrane fragments were collected by centrifugation (14000g, 30 min, 4℃), and were stored in a freezer at -80℃ for standby use after freeze-drying.
[0051] 4) 5 mg of cell membrane fragments and 10 mg of water-soluble CsLu (1-x-y) Yb x Er y F z nanoparticles were mixed into 10 mL of PBS, ultrasonicated in a water bath for 5 min, repeatedly extruded 5 times using an extruder, and finally the obtained nanoparticles were freeze-dried to construct a homologous targeting NIR-II fluorescent imaging nano-platform, which was stored in a freezer at -80℃ for standby use.
[0052] Application test
[0053] The NIR-II region fluorescent imaging nano-platform prepared in Example 1 was used to guide the surgical removal of tumors, and the specific steps were as follows:
[0054] 200 μL of 20 mg / mL of NIR-II region fluorescent imaging nano-platform material was injected into the mouse body through the tail vein, and at 12 h after injection, the mouse was anesthetized using a small animal inhalation gas anesthesia machine, and after anesthesia, the mouse was placed in a NIR-II region fluorescent imaging instrument for fluorescent imaging. Through NIR-II region fluorescent imaging, the tumor edge was marked and the mouse tumor was removed under anesthesia.
[0055] The results are shown in Figure 4 , and Figure 4The effect picture before (left) and after (right) the tumor is removed by surgery. The inset in the right picture is the image after the tumor is partially removed. It can be seen from the picture that the tumor edge is shown and the fluorescence disappears at the tumor site after the tumor is removed and the removed tumor tissue shows two-zone fluorescence under the imaging instrument, thus proving that the material can guide the removal of the tumor.
[0056] Example 2
[0057] The difference from Example 1 is that the CsLu (1-x-y) Yb x Er y F z The amount of Er(Ac)3, Yb(Ac)3, Lu(Ac)3 used in the preparation of the nanoparticles is as follows:
[0058] 0.02 mmol of Er(Ac)3, 0.38 mmol of Yb(Ac)3, 0.6 mmol of Lu(Ac)3 and 0.25 mmol of Cs2CO3 were added to a three-necked flask containing 8 mL of oleic acid and 6 mL of octadecene. The mixture was heated to 120°C under vacuum until a transparent solution was formed. Then, it was kept at room temperature under argon atmosphere for 30 min. Subsequently, it was cooled to room temperature, 6 mmol of NH4F was added, and the mixture was heated to 310°C under vacuum. It was kept at room temperature under argon atmosphere for 45 min. Subsequently, it was cooled to room temperature, an excess of ethanol was added, and it was centrifuged at 9000 rpm for 15 min. After removing the supernatant, it was washed with cyclohexane for 3 times to obtain the CsLu (1-x-y) Yb x Er y F z nanoparticles. The obtained nanoparticles have a uniform size and have NIR-II region fluorescence at 1530 nm, Figure 5 is its fluorescence spectrum.
[0059] Example 3
[0060] The difference from Example 1 is that the CsLu (1-x-y) Yb x Er y F z The amount of Er(Ac)3, Yb(Ac)3, Lu(Ac)3 used in the preparation of the nanoparticles is as follows:
[0061] 0.02 mmol Er(Ac)3, 0.78 mmol Yb(Ac)3, 0.2 mmol Lu(Ac)3 and 0.25 mmol Cs2CO3 were added into a three-neck flask containing 10 mL oleic acid, 4 mL oleylamine and 6 mL octadecene, the mixture was heated to 120°C under vacuum until a transparent solution was formed, then it was kept under argon atmosphere for 30 min, then it was cooled to room temperature, 3.25 mmol NH4F was added, the mixture was heated to 285°C under vacuum, it was kept under argon atmosphere for 45 min, then it was cooled to room temperature, excess ethanol was added, it was centrifuged at 12000 rpm for 15 min, after removing the supernatant, it was washed with ethanol and acetone for 3 times in turn, to obtain the CsLu of the example (1-x-y) Yb x Er y F z nanoparticles, the obtained nanoparticles have a size of 2.5 nm and have NIR-II region fluorescence of 1530 nm, Figure 6 is a fluorescence spectrum thereof.
[0062] Example 4
[0063] The difference from Example 1 is that the amount of CsLu (1-x-y) Yb x Er y F z in the preparation of the nanoparticles, the amount of Er(Ac)3, Yb(Ac)3 and Lu(Ac)3 is adjusted, specifically:
[0064] 0.02 mmol Er(Ac)3, 0.98 mmol Yb(Ac)3, 1 mmol Cs2CO3 were added into a three-neck flask containing 15 mL oleic acid, 3 mL oleylamine and 6 mL octadecene, the mixture was heated to 120°C under vacuum until a transparent solution was formed, then it was kept under argon atmosphere for 30 min, then it was cooled to room temperature, 5 mmol NH4F was added, the mixture was heated to 305°C under vacuum, it was kept under argon atmosphere for 45 min, then it was cooled to room temperature, excess ethanol was added, it was centrifuged at 10000 rpm for 15 min, after removing the supernatant, it was washed with ethanol, acetone and cyclohexane for 3 times in turn, to obtain the CsLu of the example (1-x-y) Yb x Er y F z nanoparticles, the obtained nanoparticles have a size of 2.5 nm and have NIR-II region fluorescence of 1530 nm, Figure 7 is a fluorescence spectrum thereof.
[0065] The above fluorescence spectrum results show that the material has a NIR-II fluorescence emission peak, which is beneficial for high-resolution near-infrared fluorescence imaging, so as to accurately guide the tumor tissue resection.
[0066] Example 5
[0067] This example is used to explore the influence of the feeding ratio of sensitizing agent Yb and activating agent Er on the luminescence intensity of the prepared nanoparticles. Specifically, different from example 1, the amount of Yb(Ac)3 was adjusted to 0.18 mmol, 0.38 mmol, 0.68 mmol and 0.98 mmol respectively, while the amount of Er(Ac)3 was unchanged (0.02 mmol), so that the ratio of Yb(Ac)3 to Er(Ac)3 was 9:1, 19:1, 34:1 and 49:1 respectively. In the case of unchanged Yb(Ac)3 (0.18 mmol), the amount of Er(Ac)3 was adjusted to 0.02 mmol, 0.10 mmol and 0.20 mmol respectively, so that the ratio of Yb(Ac)3 to Er(Ac)3 was 9:1, 9:5 and 9:10 respectively. Nanoparticles under different feeding ratios of sensitizing agent Yb and activating agent Er in this example were obtained, and their luminescence intensity was tested, and the results are shown in Tables 1, 2 and Figure 8 、 Figure 9 .
[0068] Table 1
[0069] Yb to Er feed ratio (x:y) Luminescence intensity (normalized intensity) 9:1 1.00 19:1 0.88 34:1 0.70 49:1 0.64
[0070] Table 2
[0071] Yb to Er feed ratio (x:y) Luminescence intensity (normalized intensity) 9:1 1 9:5 0.11 9:10 0.08
[0072] From Tables 1, 2 and Figure 8 、 Figure 9 It can be seen that when the amount of Er is constant, the fluorescence intensity at 1532 nm gradually decreases with the increase of the ratio of Yb; when Yb is constant, the fluorescence intensity at 1532 nm also shows a significant decreasing trend with the increase of the ratio of Er, therefore, it is necessary to strictly control the feeding ratio of sensitizing agent Yb and activating agent Er to obtain the best luminescence intensity.
[0073] Example 6
[0074] The embodiment is used to explore the influence of the ratio of Ln(Ac)3, Cs2CO3 and NH4F on the luminescence intensity of the prepared nanoparticles. Specifically, different from embodiment 1, the ratio of Ln(Ac)3, Cs2CO3 and NH4F is adjusted to 2:3:12, 1:1:5, 6:1:20 and 4:1:14 respectively, and the rest of the process is referred to embodiment 1 to obtain nanoparticles under different ratios of Er(Ac)3, Yb(Ac)3, Cs2CO3 and NH4F, test the luminescence intensity, and the results are shown in Table 2 and Figure 10
[0075] Table 3
[0076] Ln(Ac)3: Cs2CO3: NH4F Luminescence intensity (normalized intensity) 2:3:12 0.05 1:1:5 0.06 6:1:20 0.04 4:1:14 1
[0077] From Table 3 and Figure 10 It can be seen that the luminescence intensity changes greatly with the change of the ratio of Ln(Ac)3: Cs2CO3: NH4F, which is due to the change of the crystal lattice structure caused by the change of the ratio of Ln(Ac)3: Cs2CO3: NH4F, thereby causing the change of the fluorescence intensity.
[0078] Embodiment 7
[0079] The embodiment is used to explore the influence of the high-temperature holding temperature on the morphology of the prepared nanoparticles. Specifically, different from embodiment 1, the holding temperature in step 1) is adjusted to 275℃, 285℃, 295℃ and 315℃ respectively, and the rest of the process is referred to embodiment 1 to obtain nanoparticles under different high-temperature holding time conditions, and the transmission electron microscope image is shown in Figure 11 It can be seen that the material morphology obtained at 285℃ is the most regular, and the regular morphology is beneficial to the stability of the luminescence performance of the material.
[0080] In summary, the present application combines CsLu (1-x-y) Yb x Er y F z NIR-II luminescence performance of the nanoparticles and good immune escape and tumor targeting of the cancer cell membrane, and a cancer cell membrane coated CsLu (1-x-y) Yb x Er y F z nanoparticles are designed to perform NIR fluorescence imaging of tumors and guide surgical resection of tumors;
[0081] Compared with existing visible region and NIR-I region fluorescent materials, the present application has a NIR-II fluorescence emission peak, which is beneficial to high-resolution near-infrared fluorescence imaging, so that the tumor tissue can be accurately guided to be resected;
[0082] Compared with organic materials, the application has a longer light-emitting life, and has higher light stability and biocompatibility, and is not easy to be photobleached.
[0083] Compared with other target materials such as HA and polypeptides, the cancer cell membrane has the immune escape ability and homologous binding ability specific to cancer cells, has better coating effect, has better water stability, and has better accumulation effect in tumor tissues.
[0084] It should be noted that the above examples are only used to illustrate the technical solutions of the present application and are not limiting. Although the present application has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solutions of the present application can be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present application, and they should be covered in the scope of the claims of the present application.
Claims
1. A homologous targeting NIR-II region fluorescent imaging nano-platform, characterized in that: Comprising, CsLu (1-x-y) Yb x Er y F z Nanoparticles are the light emitting center, and after water-soluble treatment, the cancer cell membrane is coated on the surface by extrusion method, that is, the homologous targeting NIR-II region fluorescent imaging nano platform is formed; wherein the CsLu (1-x-y) Yb x Er y F z The value of x in the nanoparticle is 0-0.98, the value of y is 0.02-0.98, and the value of z is 4-7. The preparation method of the homologous targeting NIR-II region fluorescent imaging nano platform comprises, Lu salt, Yb salt, Er salt, Cs2CO3, oleic acid, oleylamine, and octadecene were mixed and heated under vacuum conditions until a transparent solution was formed, and then incubated under an argon atmosphere, followed by cooling to room temperature, and then NH4F was added to perform a synthesis reaction, and after the reaction was completed, washing was performed to obtain CsLu (1-x-y) Yb x Er y F z nanoparticles, the CsLu (1-x-y) Yb x Er y F z nanoparticles, wherein x has a value of 0 to 0.98, y has a value of 0.02 to 0.98, and z has a value of 4 to 7. CsLu (1-x-y) Yb x Er y F z The nanoparticles are dissolved in a non-polar or moderately polar solvent to which is added NH2-PEG 2000 -DSPE, ultrasonic mixing, to obtain water-soluble CsLu (1-x-y) Yb x Er y F z nanoparticles; The extracted cancer cell membrane is mixed with CsLu (1-x-y) Yb x Er y F z The nanoparticles are mixed in PBS, ultrasonically treated in a water bath, and repeatedly extruded through an extruder to obtain a homologous targeting NIR-II region fluorescent imaging nano platform. The molar ratio of the Yb salt and the Er salt is 9-19:1-5, and the molar ratio of the Lu salt, Cs2CO3 and NH4F is 4:1:
14.
2. The homologous targeting NIR-II region fluorescent imaging nano-platform of claim 1, wherein: The cancer cell membrane and CsLu (1-x-y) Yb x Er y F z The mass ratio of the nanoparticles is 0.5-2:
1.
3. The homologous targeting NIR-II region fluorescent imaging nano-platform of claim 2, wherein: The cancer cell membrane comprises a mouse breast cancer cell membrane and a mouse colon cancer cell membrane.
4. The homologous targeting NIR-II region fluorescent imaging nano-platform of claim 1, wherein: The salt comprises an Ac salt or a Cl salt.
5. The homologous targeting NIR-II region fluorescent imaging nano-platform of claim 1, wherein: When the amount of each oleic acid is 6-15 mL, the amount of corresponding oleylamine is 0-4 mL, and the amount of octadecene is 10-15 mL.
6. The homologous targeting NIR-II region fluorescent imaging nano-platform of claim 1, wherein: The reaction temperature of the synthesis reaction is 285-315 DEG C, and the reaction time is 45-60 min.
7. The homologous-targeting NIR-II region fluorescent imaging nano-platform of claim 1, wherein: The non-polar or moderately polar solvent comprises one of acetone, tetrahydrofuran and cyclohexane.