Photosensitizer with high singlet oxygen yield and preparation method, use method and application thereof

Abstract

The present invention belongs to the technical field of chemical catalysis, and discloses a photosensitizer with high singlet oxygen yield, which is an inorganic-organic hybrid system composed of cadmium selenide quantum dots and triplet receptor molecules anchored on the surface of cadmium selenide quantum dots. The present invention uses cadmium selenide quantum dots as sensitizers and constructs an inorganic-organic hybrid system with triplet receptor molecules. Its singlet oxygen generation rate is nearly 4 times that of single CdSe QDs, and has great application prospects in photocatalysis and photodynamic therapy.

Description

Technical Field

[0001] The invention belongs to the technical field of chemical catalysis and relates to a photosensitizer with high singlet oxygen yield and a preparation method, a use method and an application thereof. Background Art

[0002] Singlet oxygen is the excited state of oxygen molecules. It is an important active oxygen species with very strong oxidizing ability. Singlet oxygen has extremely important application value in photodynamic therapy, organic synthesis and environmental catalysis. The generation of singlet oxygen mainly relies on light to excite organic or metal organic compound photosensitizers from the ground state to the singlet excited state. The singlet state of the excited photosensitizer molecules is converted to the triplet excited state through interstitial crossing. The photosensitizer in the triplet excited state then transfers energy to the oxygen molecules, thereby generating singlet oxygen.

[0003] Photodynamic therapy is an emerging method for treating tumors, precancerous lesions, vascular diseases and proliferative skin diseases in recent years. The specific process of photodynamic therapy is to activate the photosensitizer in the tumor tissue through light of a specific wavelength. The activated photosensitizer further transfers energy to the surrounding oxygen to generate reactive oxygen species such as singlet oxygen, thereby inducing chemical damage and leading to tumor cell death. Therefore, the activity of the photosensitizer is a key factor affecting the efficiency of singlet oxygen production. Compared with the three traditional methods of tumor treatment, namely surgery, radiotherapy and chemotherapy, photodynamic therapy has the advantages of few side effects, high selectivity, good applicability and repeated treatment, and has become an effective means of treating tumors. However, there are still some problems that need to be solved, such as the difficulty in obtaining photosensitizers that can efficiently produce singlet oxygen.

[0004] Triplet energy transfer from semiconductor quantum dots to organic molecules has been shown to be an effective method for molecular triplet sensitization. Compared with the singlet to triplet gap crossing of traditional organic or metal organic compound photosensitizers, the energy loss caused by the gap crossing of semiconductor quantum dots is very small and can be ignored. In addition, the band gap size of semiconductor quantum dots can be precisely adjusted by regulating their composition and size, which greatly reduces the difficulty of quantum dots combining with molecules with different triplet energy acceptors. More importantly, the large specific surface area makes semiconductor quantum dots easy to be modified by triplet acceptor molecules, thereby achieving efficient triplet energy transfer. Based on this, the triplet energy transfer system between semiconductor quantum dots and organic molecules has potential application prospects in the generation of singlet oxygen. Summary of the invention

[0005] The present invention aims to solve the technical problem of low singlet oxygen generation efficiency of photosensitizers in the prior art, and provides a photosensitizer with high singlet oxygen yield. Cadmium selenide quantum dots are used as sensitizers, and an inorganic-organic hybrid system is constructed with triplet receptor molecules. The singlet oxygen generation rate of the photosensitizer is nearly 4 times that of CdSe QDs alone, and the photosensitizer has great application prospects in photocatalysis and photodynamic therapy.

[0006] To achieve the above object, the present invention adopts the following technical solutions:

[0007] The invention provides a photosensitizer with high singlet oxygen yield. The photosensitizer is an inorganic-organic hybrid system composed of cadmium selenide quantum dots and triplet receptor molecules anchored on the surfaces of the cadmium selenide quantum dots. The triplet receptor molecules are polycyclic aromatic hydrocarbon molecules with carboxyl groups.

[0008] In one technical solution, the triplet acceptor molecule is selected from one of 1-pyrenecarboxylic acid and 9-anthracenecarboxylic acid.

[0009] In one technical solution, the concentration ratio of the triplet acceptor molecules to the cadmium selenide quantum dots is 20-30:1.

[0010] In one technical solution, the exciton absorption peak and the fluorescence emission peak of the cadmium selenide quantum dots are located at 529 nm and 542 nm respectively, and the average diameter of the cadmium selenide quantum dots is 2.4 nm.

[0011] The present invention also provides a method for preparing the above-mentioned photosensitizer with high singlet oxygen yield, comprising the following steps: using cadmium selenide quantum dots as sensitizers, using a ligand exchange method, anchoring triplet receptor molecules to the surface of cadmium selenide quantum dots to construct an inorganic-organic hybrid system. The preparation method of cadmium selenide quantum dots is as follows: cadmium tetradecanoate and tin dioxide are placed in a three-necked flask, octadecene is added and stirred and degassed at 55°C, and after the solution becomes transparent, the reaction solution is heated to 230°C in a nitrogen environment; after reaching the target temperature, oleic acid is added, and heating is stopped after the reaction for 10 minutes. After cooling, ethanol washing is used to remove unreacted substances to obtain cadmium selenide quantum dots, which are dispersed in n-hexane for standby use.

[0012] The present invention also provides a method for using the above-mentioned photosensitizer with high singlet oxygen yield, comprising the following steps: using cadmium selenide quantum dots as sensitizers, adopting a ligand exchange method, anchoring triplet receptor molecules to the surface of the cadmium selenide quantum dots to construct an inorganic-organic hybrid system, and irradiating the inorganic-organic hybrid system to generate singlet oxygen.

[0013] The present invention also provides the use of the above-mentioned photosensitizer with high singlet oxygen yield in the preparation of drugs for photodynamic therapy of tumors.

[0014] Compared with the prior art, the present invention has the following beneficial effects:

[0015] The present invention uses cadmium selenide quantum dots as sensitizers, which have a large extinction coefficient, are simple to prepare and have adjustable sizes, and can be well matched with molecules with different triplet energies; their large specific surface area makes them easily modified by triplet acceptor molecules, thereby achieving efficient triplet energy transfer.

[0016] The present invention uses cadmium selenide quantum dots as sensitizers, which form covalent bonds with two oxygen atoms on the carboxylic acid group of triplet receptor molecules. The constructed inorganic-organic hybrid system can effectively generate singlet oxygen under light, and its singlet oxygen generation rate is nearly 4 times that of single CdSe QDs, making it have great application value in photocatalysis and photodynamic therapy. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 This is a transmission electron microscopy image of CdSe QDs prepared in Example 1.

[0018] Figure 2 This is the UV-visible absorption and fluorescence spectra of CdSe QDs prepared in Example 1.

[0019] Figure 3 This is the transmission electron microscopy image of the CdSe QDs-PCA hybrid system prepared in Example 2.

[0020] Figure 4 This is the UV-visible absorption and fluorescence spectra of the CdSe QDs-PCA hybrid system prepared in Example 2.

[0021] Figure 5 This is the fluorescence up-conversion image of the mixed solution of diphenylanthracene (DPA) and CdSe QDs-PCA in Example 2 under 532 nm continuous laser irradiation.

[0022] Figure 6 This is the fluorescence lifetime diagram of CdSe QDs and CdSe QDs-PCA hybrid system in Example 2.

[0023] Figure 7 This is the transient absorption spectrum of CdSe QDs and CdSe QDs-PCA hybrid system in Example 2.

[0024] Figure 8 Absorption spectra of DPBF under different illumination times.

[0025] Fig. 9 This is the absorption spectrum of the CdSe QDs+DPBF mixed solution and the CdSe QDs-PCA+DPBF mixed solution under 532nm continuous laser irradiation in Example 4.

[0026] Fig.10 This is the first-order degradation kinetics diagram of DBPF in the CdSe QDs system and the CdSe QDs-PCA hybrid system under the same illumination conditions in Example 4. DETAILED DESCRIPTION

[0027] The following examples are used to illustrate the present invention, but are not intended to limit the scope of the present invention. Unless otherwise specified, the technical means used in the examples are conventional means known to those skilled in the art. The test methods in the following examples are conventional methods unless otherwise specified.

[0028] Example 1 Synthesis of CdSe QDs sensitizer by high temperature hot injection method

[0029] 0.057 g (0.1 mmol) of cadmium tetradecanoate and 0.011 g (0.1 mmol) of tin dioxide were placed in a 25 ml three-necked flask, 6.3 mL of octadecene was added, and the mixture was stirred with a magnetic bar and degassed for 10 min at 55 °C. After the solution became transparent, the reaction solution was heated to 230 °C under a nitrogen atmosphere. When the reaction solution reached 230 °C, 0.1 mL of oleic acid was quickly added, and the heating was stopped after further reaction for 10 min. After the reaction solution was cooled to room temperature, it was washed with ethanol to remove the unreacted substances, thereby obtaining a CdSeQDs sensitizer protected by an oleic acid ligand, which was dispersed in n-hexane for later use.

[0030] Figure 1 This is a transmission electron microscope image of the CdSe QDs prepared in Example 1. From the image, it can be seen that the prepared quantum dots are uniform in size, and the average diameter of the quantum dots is 2.4 nm.

[0031] Figure 2 The UV-visible absorption spectrum and fluorescence spectrum of the CdSe QDs prepared in Example 1, the exciton absorption and fluorescence emission peak positions are located at 529nm and 542nm respectively.

[0032] Example 2

[0033] Take 5 ml of the CdSe QDs prepared in Example 1 and divide it into two equal parts. Add 0.5 mg of 1-pyrenecarboxylic acid (PCA) powder to one part and stir vigorously for 40-60 min. Then, filter the solution with a 0.22 µm polytetrafluoroethylene syringe filter to remove excess PCA to obtain PCA ligand-protected CdSe QDs, i.e., CdSe QDs-PCA hybrid system. The other part is used as a control.

[0034] Figure 3This is a transmission electron microscopy image of the CdSe QDs-PCA hybrid system prepared in Example 2. From the image, it can be seen that the PCA-modified CdSe QDs have good dispersibility and no aggregation occurs.

[0035] Figure 4 The UV-visible absorption and fluorescence spectra of the CdSe QDs-PCA hybrid system prepared in Example 2. As can be seen from the figure, the exciton absorption peak of CdSe QDs did not change after the exchange with the PCA ligand, but the absorption of PCA molecules appeared in the ultraviolet region, indicating the successful exchange of ligands. In addition, the fluorescence of the quantum dots was significantly quenched after the PCA ligand exchange, and the quenching rate reached 84%, indicating that the energy of CdSe QDs under light excitation was effectively transferred to the PCA molecules.

[0036] To prove Figure 4 The quenching of CdSe QDs fluorescence in the presence of PCA is caused by energy transfer from the quantum dots to the PCA triplet state. Fluorescence upconversion experiments were also performed, such as Figure 5 As shown, when diphenylanthracene (DPA, triplet energy is 1.8eV) and CdSe QDs-PCA mixed solution are excited by 532nm continuous laser, obvious blue light emission from DPA is observed, indicating that the energy of CdSe QDs is effectively transferred to the triplet state of PCA molecules under light excitation, and the PCA molecule triplet further transfers energy to the DPA molecule triplet state. Two DPA triplet molecules emit singlet fluorescence through collision annihilation, which is the observed blue light. The inset is a real picture of the mixed solution under light excitation, with a 500nm short-wave filter in front of the sample, from which the blue light emission under light excitation can be clearly seen. In particular, because DPA and PCA molecules have no absorption at 532nm, 532nm can only excite CdSe QDs.

[0037] Figure 6 The fluorescence lifetime diagram of CdSe QDs and CdSe QDs-PCA hybrid system in Example 2. The fluorescence lifetime of the sample was obtained under 440nm light excitation. The PCA molecule has no absorption at 440nm, so 440nm can only excite CdSe QDs. It can be seen from the figure that under the same test conditions, compared with the single CdSe QDs, the fluorescence lifetime decay rate of the CdSe QDs-PCA hybrid system is significantly accelerated, which also indicates that the energy of CdSe QDs is transferred to the acceptor PCA molecule under light excitation.

[0038] Figure 7Figure 2 is the transient absorption spectrum of CdSe QDs and CdSe QDs-PCA hybrid system in Example 2. The transient spectrum was obtained under 470nm excitation, and 470nm can only excite CdSe QDs. Figure 7 As can be seen in a and 7b, under the same test conditions, when PCA molecules exist, the recovery of the CdSe QDs exciton bleaching peak is significantly accelerated. From 7c, it can be more intuitively seen that the exciton dynamics decay rate of CdSe QDs is faster after PCA functionalization, further proving that the energy of photoexcited CdSeQDs is effectively transferred to the triplet state of PCA molecules.

[0039] Example 3 Using UV-Visible Absorption Spectrophotometry to Detect the Stability of DPBF Under Illumination

[0040] 1,3-Diphenylisobenzofuran (DPBF) was used as a probe to detect the generation of singlet oxygen. DPBF reacts with singlet oxygen and its absorption peak at 410nm decreases. 4.5mM / L, 100µl 1,3-diphenylisobenzofuran (DPBF) was added to 1.8mL n-hexane solution and irradiated under 532nm continuous laser. The absorption spectrum of DPBF solution under different illumination time was tested by UV-visible spectrophotometer. The stability was judged by observing the change of its absorption spectrum over time.

[0041] As a blank control, Figure 8 The absorption spectra of DPBF under different illumination times. It can be seen that the absorption spectrum of DPBF does not change with the increase of illumination time, which means that DPBF does not degrade under illumination.

[0042] Example 4: Detection of singlet oxygen generation capacity in CdSe QDs and CdSe QDs-PCA hybrid system by UV-visible absorption spectrophotometry

[0043] Take 1.8mL of n-hexane solution of equal amounts of CdSe QDs and CdSe QDs-PCA hybrid system, and ensure that the exciton absorbance of CdSeQDs and CdSe QDs-PCA hybrid solutions is equal (0.22) in the experiment, and add an equal amount of DPBF 100µL to the above solution. Use 532nm continuous laser to irradiate the mixed solution of CdSe QDs and CdSe QDs-PCA containing DPBF under the same conditions, and use UV-visible spectrophotometer to test the change of the absorption spectrum of the mixed solution over time. The effect of singlet oxygen generation is judged by the change of the absorption peak of DPBF at 410nm.

[0044] like Fig. 9a and 9b are the absorption spectra of CdSeQDs+DPBF mixed solution and CdSe QDs-PCA+DPBF mixed solution under 532nm continuous laser irradiation, respectively. As can be seen from the figure, the absorbance of the characteristic peak of DPBF at 410nm gradually decreases with the increase of illumination time, indicating that singlet oxygen is generated in the system under illumination. In addition, compared with the single CdSe QDs system, the absorbance of the characteristic peak of DPBF in the CdSe QDs-PCA hybrid system under the same illumination conditions decreases rapidly, indicating that the generation rate of singlet oxygen in the CdSeQDs-PCA hybrid system under illumination is faster. This is because the triplet energy transferred from CdSe QDs to PCA molecules under light excitation can be further transferred to ground state oxygen molecules, thereby effectively improving the generation efficiency of singlet oxygen. More importantly, we can observe that the exciton absorption peak of CdSe QDs is almost unchanged under illumination conditions, which shows that CdSe QDs have excellent photostability.

[0045] Fig.10 The first-order degradation kinetics (410 nm) of DBPF in the CdSe QDs system and the CdSe QDs-PCA hybrid system under the same illumination conditions, the slopes of the straight lines extracted by linear fitting of the kinetics are -0.104 and -0.403 respectively. Since the degradation rate of DBPF is proportional to the generation rate of singlet oxygen in the system, it can be obtained that the singlet oxygen generation rate of the CdSe QDs-PCA hybrid system is nearly 4 times that of CdSe QDs alone.

[0046] The embodiments described above are only preferred embodiments of the present invention and are only used to explain the present invention, not to limit the scope of implementation of the present invention. For those skilled in the art, other implementation methods can certainly be easily made by replacement or modification based on the technical contents disclosed in this specification. Therefore, all changes and improvements made on the principles of the present invention should be included in the scope of the patent application of the present invention.

Claims

1. Use of a photosensitizer with a high singlet oxygen yield in the preparation of a drug for photodynamic therapy of tumors, characterized in that: The photosensitizer is an inorganic-organic hybrid system composed of cadmium selenide quantum dots and 1-pyrene carboxylic acid anchored on the surface of the cadmium selenide quantum dots. The photosensitizer is dispersed in normal hexane, and the singlet oxygen generation rate of the photosensitizer is four times that of the single cadmium selenide quantum dots.

2. The use according to claim 1, characterized in that: The concentration ratio of the 1-pyrenecarboxylic acid to the cadmium selenide quantum dots is 20-30:

1.

3. The use according to claim 1, characterized in that: The exciton absorption peak and the fluorescence emission peak of the cadmium selenide quantum dots are located at 529 nm and 542 nm respectively, and the average diameter of the cadmium selenide quantum dots is 2.4 nm.

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