CN113975391B - Self-oxygen-supply photosensitizer and preparation method and application thereof - Google Patents
Self-oxygen-supply photosensitizer and preparation method and application thereof Download PDFInfo
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- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
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Abstract
The invention provides a self-oxygen supply photosensitizer and a preparation method and application thereof. The self-oxygen supply photosensitizer prepared by the invention can improve the biocompatibility of the near-infrared photosensitizer, supply oxygen as required to improve the problem of tissue hypoxia, and can realize deep photodynamic therapy through effective delivery of the near-infrared photosensitizer.
Description
Technical Field
The invention belongs to the technical field of photosensitizers, and particularly relates to a preparation method and application of a self-oxygen-supplying photosensitizer.
Background
Cancer has been one of the diseases harmful to human health, and in recent years, photodynamic therapy (PDT) has attracted much attention due to its advantages of minimal invasion, low side effects, and high spatial selectivity. The problems of hypoxia of solid tumor, poor enrichment effect of drug at tumor, poor drug permeability in tumor, and limited penetration depth of light source for exciting Photosensitizer (PS) become the most important factors for limiting PDT development. At present, the nano composite diagnosis and treatment material which releases drugs, photosensitizer, oxygen and the like by using Tumor Microenvironment (TME) triggering or light triggering becomes a research hotspot.
At present, although the photosensitizer is widely improved, the photosensitizer still has the defects of poor dark toxicity and light stability and the like under complex physiological conditions and high active oxygen environments. Most photosensitizers often suffer from aggregation-induced fluorescence quenching and a dramatic drop in the yield of reactive oxygen species in the aggregated state due to their inherent rigid planar and hydrophobic structure. To a certain extent, limits the antitumor applications of PDT. In addition, the prior art has the problems of complex preparation of the required nano composite material, low oxygen carrying rate, uncontrolled oxygen release and the like.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides the vermiculite nanosheet diagnosis and treatment agent with the near-infrared light control oxygen supply as required, which not only can improve the biocompatibility of the near-infrared photosensitizer, but also can ensure that the nano diagnosis and treatment agent supplies oxygen as required to improve the problem of tissue hypoxia, and can also realize deep photodynamic therapy through effective delivery of the near-infrared photosensitizer.
The method is realized by the following technical scheme:
the self-oxygen supply photosensitizer structurally comprises vermiculite nanosheets and aggregation-induced emission luminescent agents loaded on the surfaces of the vermiculite nanosheets.
Further, the aggregation-induced emission luminescent agent is one or more of DCPy, DCMa, DCIs and DCFu,
wherein the structural formula of the DCPy is shown as
The structural formula of DCMa is
The structural formula of the DCIs is
The structural formula of the DCFu is
Preferably, the aggregation-inducing luminescent agent is DCPy.
Further, the vermiculite nanosheet is of a single-layer structure or a multi-layer structure.
Further, the loading amount of the aggregation-induced emission luminescent agent is 10-15w/w% of the weight of the vermiculite nanosheets.
The invention also provides a preparation method of the self-oxygen-supply photosensitizer, which comprises the following steps:
s1: synthesizing vermiculite nanosheets by a lithium ion intercalation method;
s2: and loading the aggregation-induced emission luminescent agent on the surface of the vermiculite nanosheet to obtain the self-oxygen-supplying photosensitizer.
Further, step S1 includes: and adding vermiculite into a lithium salt solution modifier to obtain vermiculite nanosheets.
Preferably, the alkali metal salt solution modifier is one or more of a lithium chloride solution, a lithium ethylenediamine tetraacetate solution or a lithium citrate solution.
Further, in step S2, the ratio of the concentration of the vermiculite nanosheet to the concentration of the aggregation-induced emission luminescent agent is 2: (0.1-100).
Further, in step S2, an aggregation-induced emission luminescent agent is loaded on the surface of the vermiculite nanosheet by electrostatic adsorption.
The invention also provides the application of the self-oxygen-supply photosensitizer in preparing photodynamic therapy medicines.
The beneficial effects of the invention comprise the following aspects:
1. the self-oxygen-supplying photosensitizer provided by the invention can improve the photodynamic therapy effect, more importantly, the self-oxygen-supplying photosensitizer controls the fixed-point timed release of oxygen through the vermiculite nano material, can be effectively used for diagnosis and treatment of cancer cells and tumors, and has a better in-vivo biomedical application prospect;
2. the self-oxygen-supplying photosensitizer provided by the invention has good biocompatibility and high specific surface area, and has good application prospect in the aspect of visual photodynamic therapy;
3. the self-oxygen-supplying photosensitizer provided by the invention has the advantages of rich raw materials, easiness in preparation and wide application range, and can be used for industrial production.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present application, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present application, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without creative efforts.
FIG. 1 is a schematic structural view of a self-oxygen supplying photosensitizer prepared in example 1;
FIG. 2 is a transmission electron microscope photograph of the self-oxygenating photosensitizer prepared in example 1;
FIG. 3 is an atomic force microscope image of the self-oxygenating photosensitizer prepared in example 1;
FIG. 4 is a graph of the average particle size and average height of the self-oxygen supplying photosensitizer prepared in example 1;
FIG. 5 is a visible-near infrared spectrum and a fluorescence spectrum of the self-oxygenating photosensitizer prepared in example 1;
FIG. 6 is an X-ray photoelectron spectrum of the self-oxygen-supplying photosensitizer prepared in example 1;
FIG. 7 is a Zeta potential diagram of the self-oxygenating photosensitizer prepared in example 1;
FIG. 8 is the oxygen production concentration of the self-oxygenating photosensitizer prepared in example 1;
FIG. 9 is a diagram of a self-oxygenating photosensitizer prepared in example 1 1 O 2 Electron spin resonance amplitude;
FIG. 10 is the. OH electron spin resonance amplitude of the self-oxygenating photosensitizer prepared in example 1;
FIG. 11 is a diagram of a Confocal Laser Scanning Microscope (CLSM) in Experimental example 3;
FIG. 12 is time lapse bioimaging of Balb/c mice;
FIG. 13 is a bioimaging of major organs and tumors after 24 hours of intravenous injection;
FIG. 14 is the mean fluorescence intensity measurements of DCPy and NSs @ DPCy on major organs and tumors in mice;
FIG. 15 is a graph of tumor growth after systemic administration of PBS, NSs, DCPy and NSs-DCPy to a live mouse for 5 minutes without or with light;
FIG. 16 is a graph showing the results of immunohistochemical analysis of Caspase3 expression (scale bar 100 μm);
FIG. 17 is a graph of the results of immunohistochemical analysis of GPX4 expression (scale bar 100 μm);
FIG. 18 is hematoxylin and eosin stained images (scale bar 1000 μm) obtained from heart, liver, spleen, lung and kidney of different groups of living mice;
FIG. 19 shows the measurement results of the mean corpuscular hemoglobin concentration;
FIG. 20 is the mean platelet volume measurement;
FIG. 21 shows the measurement results of hemoglobin concentration;
FIG. 22 is a result of a white blood cell count assay;
FIG. 23 is the result of the mean corpuscular hemoglobin measurement;
FIG. 24 shows the result of analysis of the coefficient of variation of the distribution width of erythrocytes;
FIG. 25 shows the results of red blood cell assay;
FIG. 26 is the platelet assay results;
FIG. 27 shows the results of urea nitrogen measurement;
FIG. 28 shows the results of aspartate aminotransferase assay;
FIG. 29 shows the results of glutamic-pyruvic transaminase assay;
fig. 30 shows albumin measurement results.
Detailed Description
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be obtained by a person skilled in the art without making any creative effort based on the embodiments in the present invention, belong to the protection scope of the present invention.
Since the efficiency of photodynamic therapy (PDT) of tumors depends on oxygen concentration, PDT treatment techniques are limited by hypoxia. In order to overcome the tumor hypoxia-induced PDT drug resistance, the invention provides a novel oxygen self-sufficient photodynamic cancer treatment strategy. Vermiculite Nano Sheets (NSs) are synthesized by adopting a simple lithium ion intercalation method, and then aggregation induced luminescence (DCPy) is loaded on the surfaces of the nano sheets through electrostatic adsorption. Once NSs @ DPCy is absorbed by hypoxic tumor cells, and exposed to visible light, NSs not only catalyzes the decomposition of hydrogen peroxide to generate oxygen, but also catalyzes hydrogen peroxide and oxygen to generate a plurality of reactive oxygen species ROS (& OH & Oh) 1 O 2 ). In addition, NSs continuously generate oxygen, relieve hypoxia, and greatly improveThe therapeutic effect of PDT. Interestingly, NSs are able to regulate the Tumor Microenvironment (TME) by consuming glutathione, which causes tumor cell ferroptosis. Therefore, the invention provides a new method for synthesizing the vermiculite nano-sheets NSs, and develops an intelligent treatment platform based on the vermiculite nano-sheets NSs, which is used for treating iron poisoning auxiliary oxygen self-sufficient photodynamic cancer.
Example 1
The self-oxygen-supplying photosensitizer has a structure comprising vermiculite nanosheets and aggregation-induced emission luminescent agent DCPy loaded on the surfaces of the vermiculite nanosheets, wherein the DCPy has a structural formula
The layer number of the vermiculite nano-sheets is 1, and the loading capacity of the aggregation induced emission luminescent agent is 10.1w/w% of the weight of the vermiculite nano-sheets.
The preparation method comprises the following steps:
s1, synthesizing vermiculite nanosheets by a lithium ion intercalation method:
s2, loading an aggregation-induced emission luminescent agent on the surface of the vermiculite nanosheet: 200 μ g/mL vermiculite Nanoplatelets (NSs) dispersion was mixed with 1.0mg/mL DCPy in PBS, sonicated for 30min, and stirred overnight at room temperature. Excess was discharged in Amicon tubes (MWCO 100kDa, millipore), 3500rpm, for 30 minutes, and then washed three times with PBS to obtain a self-oxygenating photosensitizer.
The concentration of DCPy was determined by subtracting the corresponding NSs peak from the UV-visible absorption spectrum at 452 nm.
The invention also provides the application of the oxygen supply photosensitizer in preparing photodynamic therapy medicines.
Example 2
The self-oxygen-supplying photosensitizer has a structure comprising vermiculite nanosheets and aggregation-induced emission luminescent agent DCPy loaded on the surfaces of the vermiculite nanosheets, wherein the DCPy has a structural formula
The number of the vermiculite nano-sheets is 2, and the loading capacity of the aggregation-induced emission luminescent agent is 12w/w% of the weight of the vermiculite nano-sheets.
The preparation method comprises the following steps:
s1, synthesizing vermiculite nanosheets by a lithium ion intercalation method:
s2, loading an aggregation-induced emission luminescent agent on the surface of the vermiculite nanosheet: 200 μ g/mL vermiculite Nanoplatelets (NSs) dispersion was mixed with DCPy at a concentration of 2.0mg/mL in PBS, sonicated for 30min, and stirred overnight at room temperature. Excess was discharged in Amicon tubes (MWCO 100kDa, millipore), 3500rpm, for 30 minutes, and then washed three times with PBS to obtain a self-oxygenating photosensitizer.
The concentration of DCPy was determined by subtracting the corresponding NSs peak from the UV-visible absorption spectrum at 452 nm.
The invention also provides the application of the oxygen supply photosensitizer in preparing photodynamic therapy medicaments.
Example 3
The self-oxygen-supplying photosensitizer has a structure comprising vermiculite nanosheets and aggregation-induced emission luminescent agent DCPy loaded on the surfaces of the vermiculite nanosheets, wherein the DCPy has a structural formula
The number of the vermiculite nanosheets is 3, and the loading amount of the aggregation-induced emission luminescent agent is 15w/w% of the weight of the vermiculite nanosheets.
The preparation method comprises the following steps:
s1, synthesizing vermiculite nanosheets by a lithium ion intercalation method:
s2, loading an aggregation-induced emission luminescent agent on the surface of the vermiculite nanosheet: 200 μ g/mL vermiculite Nanoplatelets (NSs) dispersion was mixed with 10mg/mL DCPy in PBS, sonicated for 20min, and stirred overnight at room temperature. Excess was discharged in Amicon tubes (MWCO 100kDa, millipore), 3500rpm, for 30 minutes, and then washed three times with PBS to obtain a self-oxygenating photosensitizer.
The concentration of DCPy was determined by subtracting the corresponding NSs peak from the UV-visible absorption spectrum at 452 nm.
The invention also provides the application of the oxygen supply photosensitizer in preparing photodynamic therapy medicaments.
Example 4
The self-oxygen-supplying photosensitizer has a structure comprising vermiculite nanosheets and aggregation-induced emission luminescent agent DCPy loaded on the surfaces of the vermiculite nanosheets, wherein the DCPy has a structural formula
The number of the vermiculite nanosheets is 1, and the loading amount of the aggregation-induced emission luminescent agent is 10w/w% of the weight of the vermiculite nanosheets.
The preparation method comprises the following steps:
s1, synthesizing vermiculite nanosheets by a lithium ion intercalation method:
s2, loading an aggregation-induced emission luminescent agent on the surface of the vermiculite nanosheet: 200 μ g/mL vermiculite Nanoplatelets (NSs) dispersion was mixed with DCPy at a concentration of 0.01mg/mL in PBS, sonicated for 30min, and stirred overnight at room temperature. Excess was discharged in Amicon tubes (MWCO 100kDa, millipore), 3500rpm, for 30 minutes, and then washed three times with PBS to obtain a self-oxygenating photosensitizer.
The concentration of DCPy was determined by subtracting the corresponding NSs peak from the UV-visible absorption spectrum at 452 nm.
The invention also provides the application of the oxygen supply photosensitizer in preparing photodynamic therapy medicines.
Experimental example 1
Extracellular O 2 Production test: h at a final concentration of 10mM 2 O 2 Adding NSs @ DCPy, DCPy and NSs with final concentration of 0.2mg/mL into the solution, and measuring O generated by the solution with a dissolved oxygen meter 2 . Referring to FIG. 8, it can be seen that the oxygen production of the NSs @ DCPy group is much greater than that of the DCPy and NSs groups. It can be shown that the self-oxygen-supplying photosensitizers provided by the present inventionThe agent has excellent oxygen supply capacity.
Experimental example 2
In the nanosheets provided in example 1, due to Al 3+ The substitution of impurities causes a negative charge on the NSs layer, and due to electrostatic interactions, the AIE photosensitizer DCPy can be electrostatically attracted to the negatively charged surface of NSs, as shown in fig. 1. Fig. 2 and 3 are the surface morphologies of nss @ dcpy characterized by Transmission Electron Microscopy (TEM) and Atomic Force Microscopy (AFM), respectively. From FIG. 4 it can be seen that the average width of NSs @ DCPy is 320nm and the average height of NSs is about 1.2nm. The reason for the slight thickening of NSs is the small amount of DCPy coating on the NS surface. The coating amount of DCPy on the surface of NSs is 10.1% (w/w%) of that of NSs @ DCPy, and the coating amount is determined by the absorbance of NSs @ DCPy. The optical properties of NSs @ DCPy were evaluated by UV-visible-near IR spectroscopy and fluorescence spectroscopy as shown in FIG. 5, where the numbers 1-3 represent the absorbance of NSs, DCPy, NSs @ DCPy, respectively, and the numbers 4-6 represent the fluorescence emission intensity of NSs, DCPy, NSs @ DCPy, respectively, as can be seen from the results, NSs @ DCPy exhibits a broad absorption band from UV to near IR. In addition, NSs @ DCPy has a broader luminescence band at 672nm and the fluorescent portion of the loaded DCPy is quenched, probably due to the strong interaction between DCPy and vermiculite NSs. The chemical composition and crystal structure of NSs @ DCPy are further confirmed by X-ray photoelectron spectroscopy (XPS), as shown in FIG. 6, 1 represents the X-ray photoelectron spectrum of NSs, 2 represents the X-ray photoelectron spectrum of NSs @ DCPy, and as can be seen from FIG. 6, the peak position of NSs @ DCPy consistent with NSs represents that the main elements of the two materials are the same. As shown in fig. 7, DCPy has a zeta potential of +12.8mV in Phosphate Buffered Saline (PBS), which presumably has a positive charge characteristic that promotes the adsorption of negatively charged NSs materials by electrostatic interactions. The zeta potential of NSs was measured (FIG. 7), and an increase in the surface charge of NSs @ DCPy (-40.3 mV vs-45.4 mV) relative to the previous NSs was observed, indicating that NSs successfully modified DCPy. Further, as shown in FIG. 8, the ordinate represents the oxygen content, illustrating Fe 3+ And H 2 O 2 Can continuously generate O by oxidation-reduction reaction between 2 And oxygen deficiency in the tumor microenvironment is relieved. Considering OH and 1 O 2 has short life cycle,The chemical activity is high, and the kind of ROS is further detected by adopting a very reliable Electron Paramagnetic Resonance (EPR) technology. Two ROS (. OH and 1 O 2 ) All showed obvious EPR signals, further indicating that NSs @ DCPy has stronger ROS generating ability (FIG. 9,10).
Experimental example 3
To explore the subcellular location of the prepared nss @ dcpy in living cells (fig. 11), MC38 cells were co-stained with nss @ dcpy and different commercial organelle-specific fluorescent probes (Mito Tracker Green for mitochondrial staining, ER Tracker Green for endoplasmic reticulum staining, lyso Tracker Green for lysosomal staining). The results show that the red fluorescence of nss @ dcpy has higher co-localization with the green fluorescence of Mito Tracker green, ER Tracker green and Lyso Tracker green (the Pearson correlation coefficient of mitochondria is 0.900, the Pearson correlation coefficient of endoplasmic reticulum is 0.906, and the Pearson correlation coefficient of lysosomes is 0.846). Co-localization experiments indicate that NSs @ DCPy can enter cancer cells and accumulate widely in multiple organelles.
Experimental example 4
MC38 tumor-bearing BALB/c mice were divided into 8 groups (5 per group) (1) PBS (20. Mu.L); (2) PBS (20 μ L) + (white light 90mW/cm2,5 min); (3) NSs (20 mg/kg, 20. Mu.L); (4) NSs (20 mg/kg, 20. Mu.L) + (white light 90mW/cm2,5 min); (5) DCPy (20 mg/kg, 20. Mu.L); (6) DCPy (20 mg/kg, 20. Mu.L) + (white light 90mW/cm2,5 min); (7) NSs @ DCPy (20 mg/kg, 20. Mu.L); (8) NSs @ DCPy (20 mg/kg, 20. Mu.L) + (white light 90mw/cm2,5 min). These mice received intravenous injections of different solutions. After 12h, the tumor area was illuminated with white light. Mice tumor volume and weight were recorded every 2 days. These mice were sacrificed on day 14 to obtain major organs, blood and tumors for examination.
Biodistribution of DCPy and nss @ DCPy was evaluated in MC38 tumor-bearing mice (n = 3/group). An IVIS small animal imaging system with Cy5 channel was used to visualize the biodistribution profile of these animals at 1, 12 and 24 hours post injection. Another group of mice was sacrificed 24h later and tumor and major organ specimens were collected for tissue specific imaging (fig. 12-14). FIG. 12 is time-lapse bioimaging of BALB/c mice, wherein the tumor sites are marked with white dashed lines; fig. 13 is a bioimaging of the major organs and tumors of mice after 24 hours of intravenous injection, wherein H denotes the heart; li represents liver; s represents spleen; lu denotes lung; k represents kidney; t represents a tumor. The average fluorescence intensity of DCPy and NSs @ DPCy measured by the graph in the main organ and the tumor part is processed into a data map to obtain a data map, and the data map 14 shows that the NSs @ DCPy group has stronger signals than the DCPy group, and further proves the in vivo targeting effect of the NSs @ DCPy through blood circulation and the Enhanced Permeability Retention (EPR) effect of the drug carrier NSs.
To further evaluate the anti-tumor effect of nss @ dcpy, tumor-bearing mice were randomly divided into the following treatment groups, (1) PBS (20 μ L); (2) PBS (20. Mu.L) + (white light 90mW/cm 2 5 min); (3) NSs (20 mg/kg, 20. Mu.L); (4) NSs (20 mg/kg, 20. Mu.L) + (white light 900mW/cm 2 5 min); (5) DCPy (20 mg/kg, 20. Mu.L); (6) DCPy (20 mg/kg, 20. Mu.L) + (white light 900 mW/cm) 2 5 min); (7) NSs @ DCPy (20 mg/kg, 20. Mu.L); (8) NSs @ DCPy (20 mg/kg, 20. Mu.L) + (white 900mW/cm 2 ,5min)。
(4) After the mice of the groups (6) and (8) are injected with the treatment medicine for 12 hours, white light (90 mW/cm) 2 ) The tumor area of the mice was irradiated for 5min, and the groups (1) and (7) were not irradiated with light. Tumor volume and body weight were recorded every other day during the 14 day treatment. The tumor volume recordings are shown in FIG. 15, where dark is indicated by dark and light is indicated by light. The tumor volumes in the PBS, NSs + light and NSs @ DCPy (dark) groups increased rapidly with almost the same increase. Demonstrating that neither NSs irradiation alone nor NSs @ dcpy irradiation inhibited tumor growth compared to the control (PBS). The therapeutic effect of the DCPy + light group (PDT only) was superior to that of the NSs + light group (iron droop only), which may be associated with limited NSs concentration. The nss @ dcpy + light group (under dual synergistic effects of PDT and iron droop) showed the best tumor suppression.
To further validate the tumor inhibitory effect of PDT in combination with iron ptosis treatment, nss @ dcpy + light treated mice were sacrificed on day 1 after complete tumor ablation. The proliferation activity of the tumor was detected by hematoxylin-eosin (H & E) and immunohistochemical staining.
The immunohistochemical analysis results of Caspase-3 (Caspase 3) and GPX4 on the mouse dissected tumor tissues are shown in FIGS. 16 and 17, and the NSs @ DCPy + light group tumor cells were most significantly apoptotic compared to the other groups. Immunohistochemical staining results of tumor tissue sections show that GPX4 is obviously down-regulated (brown part is reduced) under the irradiation of NSs @ DCPy + light, and the treatment effect is remarkably attributed to iron droop. The NSs @ DCPy + light group showed significant tumor growth inhibition with PDT assistance. These results strongly demonstrate that nss @ dcpy, through a synergistic treatment of the PDT and iron ptosis pathways, is able to inhibit the proliferation of cancer cells and damage tumor vascular tissue. In addition, the body weight of each group of mice increased slowly, and no mice died during the treatment period, confirming that there were no significant side effects of all treatments.
The H & E staining image of the major organs (heart, liver, spleen, lung and kidney) is shown in FIG. 18, and it can be seen from FIG. 18 that the H & E staining results of the major organs of the mice in each group are similar to that of the PBS group and the morphology is intact no matter the mice are treated with NSs, DCPy or NSs @ DCPy under the condition of no light or light, which further proves that NSs @ DCPy has good biocompatibility (FIG. 18). In addition, through routine blood analysis and biochemical blood analysis (including items of detection and analysis of average erythrocyte hemoglobin concentration, average platelet volume, hemoglobin concentration, white blood cell count, average erythrocyte hemoglobin concentration, erythrocyte distribution width variation coefficient, erythrocytes, platelets, urea nitrogen, aspartate aminotransferase, glutamate pyruvate transaminase and albumin), toxicity of all treatment methods can be ignored, and data of each group are almost in a normal range (figures 19-30), so that the treatment safety and the non-toxicity of NSs @ DCPy are further explained.
In conclusion, the self-oxygen-supplying photosensitizer provided by the invention can improve the photodynamic therapy effect, more importantly, the self-oxygen-supplying photosensitizer controls the fixed-point timed release of oxygen through the vermiculite nano material, can automatically gather at a tumor part, can be effectively used for diagnosis and treatment of cancer cells and tumors, and has a good in-vivo biomedical application prospect; the self-oxygen-supplying photosensitizer provided by the invention has good biocompatibility and high specific surface area, and has good application prospect in the aspect of visual photodynamic therapy; in addition, the self-oxygen-supplying photosensitizer provided by the invention has the advantages of rich raw materials, easiness in preparation and wide application range, and can be used for industrial production.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (8)
1. The self-oxygen-supply photosensitizer is characterized in that the structure of the self-oxygen-supply photosensitizer comprises vermiculite nanosheets and aggregation-induced emission luminescent agents loaded on the surfaces of the vermiculite nanosheets, wherein the loading amount of the aggregation-induced emission luminescent agents is 5-55w/w% of the weight of the vermiculite nanosheets;
the aggregation-induced emission luminescent agent is one or more of DCPy, DCMa, DCIs and DCFu;
wherein the structural formula of the DCPy is shown in the specification
The structural formula of DCMa is
The structural formula of the DCIs is shown in the specification
The structural formula of the DCFu is
2. The self-oxygenating photosensitizer of claim 1 wherein the aggregation-inducing luminescent agent is DCPy.
3. The self-oxygenating photosensitizer according to claim 1, wherein the vermiculite nanosheets are of a single layer structure or a multi-layer structure.
4. A method for preparing a self-oxygen supplying photosensitizer according to any one of claims 1 to 3, comprising the steps of:
s1: synthesizing vermiculite nano sheets by a lithium ion intercalation method;
s2: and loading the aggregation-induced emission luminescent agent on the surface of the vermiculite nanosheet to obtain the self-oxygen-supplying photosensitizer.
5. The method for preparing a self-oxygen supplying photosensitizer according to claim 4, wherein the step S1 comprises: and adding vermiculite into a lithium salt solution modifier to obtain vermiculite nanosheets.
6. The method of preparing a self-oxygen-supplying photosensitizer according to claim 4, wherein in step S2, the ratio of the concentration of vermiculite nanosheets to the concentration of aggregation-induced emission luminescent agent is 2: (0.1-100).
7. The method for preparing a self-oxygen-supplying photosensitizer according to claim 4, wherein in step S2, an aggregation-induced emission luminescent agent is loaded on the surface of the vermiculite nanosheet by electrostatic adsorption.
8. Use of the self-oxygenating photosensitizer according to any one of claims 1 to 3 or prepared by the method according to any one of claims 4 to 7 in the preparation of a medicament for photodynamic therapy.
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