Pyridone intercalated cobalt-manganese hydrotalcite with singlet oxygen generation, storage and slow release functions and preparation method of pyridone intercalated cobalt-manganese hydrotalcite
By assembling pyridone molecules between cobalt-manganese hydrotalcite layers to form pyridone intercalated cobalt-manganese hydrotalcite nanomaterials, the problem of short singlet oxygen life in photodynamic therapy is solved, the slow and continuous release of singlet oxygen is achieved, and the treatment efficiency is improved.
Patent Information
- Application Number
- CN202411430994.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-10-14
- Publication Date
- 2025-02-25
AI Technical Summary
Existing nanoformulations have short singlet oxygen life during photodynamic therapy (PDT), resulting in inefficient treatment.
Pyridone intercalated cobalt-manganese hydrotalcite (Pyr-CoMn-LDH) is used to assemble pyridone molecules between its layers to form nanomaterials with singlet oxygen generation, storage and sustained release functions. The material converts oxygen into singlet oxygen under 980 nm laser irradiation and captures and slowly releases singlet oxygen through a reversible Diels-Alder reaction.
The slow and continuous release of singlet oxygen is achieved, which extends the activity time of oxygen and improves the treatment efficiency of photodynamic therapy.
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Figure CN119499371A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the technical field of preparation of nano medical materials, and specifically relates to a pyridone intercalated cobalt-manganese hydrotalcite with singlet oxygen generation, storage and sustained release functions and a preparation method thereof. Background Art
[0002] Photodynamic therapy (PDT) is one of the important treatment methods for tumors. It is a less invasive and localized treatment method that increases the chance of selective action. In the dominant type II photodynamic reaction, singlet oxygen produced by photosensitizers after being irradiated with light is the main therapeutic agent. However, most therapeutic drugs release the singlet oxygen produced in a burst manner, and its half-life is only 3.5 µs. The instantaneous release of reactive oxygen is not enough to fully kill tumor cells, which seriously restricts the therapeutic effect of PDT. Therefore, it is particularly important to develop nanoformulations with the function of efficiently generating and slowly releasing singlet oxygen to enhance the effect of PDT.
[0003] With the rapid development of nanotechnology, the application of inorganic nanomaterials in PDT has been widely explored. Layered double hydroxides (LDH) have many physical and chemical advantages such as excellent biocompatibility, pH-sensitive biodegradability, highly adjustable layer element composition and interlayer anions, and easy to form complexes with other materials, and are used in the field of PDT. However, LDH derivatives with singlet oxygen sustained release function have not been reported, and it is of great significance to develop LDH preparations with singlet oxygen generation and sustained release properties. Summary of the invention
[0004] The present invention aims to solve the problem of low therapeutic efficiency caused by short singlet oxygen lifetime in existing nano-preparations during photodynamic therapy (PDT), and provides a pyridone intercalated cobalt-manganese hydrotalcite with singlet oxygen generation, storage and sustained release functions and a preparation method thereof.
[0005] The present invention adopts the following technical solution: A pyridone intercalated cobalt manganese hydrotalcite with singlet oxygen generation, storage and sustained release functions, wherein the intercalated hydrotalcite is a thin layer of CoMn-LDH, and pyridone molecules are assembled between the layers to obtain pyridone intercalated cobalt manganese hydrotalcite Pyr-CoMn-LDH, wherein the pyridone intercalated cobalt manganese hydrotalcite has a hexagonal thin layer structure; The pyridone intercalated cobalt manganese hydrotalcite efficiently converts oxygen into singlet oxygen under 980 nm laser irradiation, and the intercalated pyridone molecules act as "singlet oxygen reservoirs" to quickly and efficiently capture and slowly release singlet oxygen through a reversible Diels-Alder reaction.
[0006] A method for preparing pyridone intercalated cobalt-manganese hydrotalcite with singlet oxygen generation, storage and sustained release functions comprises the following steps: In the first step, cobalt nitrate hexahydrate and manganese chloride tetrahydrate were added to ultrapure water and stirred at 40°C for 10 min to obtain a salt solution; In the second step, PVP was added into ultrapure water and magnetically stirred in a 40°C water bath until completely dissolved. Under stirring, the salt solution was added dropwise into the PVP solution and stirring was continued for 30 min to obtain a mixed salt solution. In the third step, NaOH was dissolved in ultrapure water and stirred at 40 °C for 10 min to obtain an alkaline solution; Step 4: adding the mixed salt solution dropwise into the alkaline solution under 65°C conditions with ultrasonic dispersion and stirring at a frequency of 50 kHz until the pH value of the solution reaches 12; Step 5: After the addition is completed, the reaction temperature is maintained at 65-85°C and the hydrothermal reaction is carried out for 3-12 hours; Step 6: After the reaction is completed, the product is collected by centrifugation, washed with ultrapure water and ethanol respectively, and dried in an electric blast drying oven at 60°C for 6 h to obtain CoMn-LDH; Step 7: Disperse CoMn-LDH in ultrapure water, perform ultrasonic dispersion for 5 min, add pyridone to the dispersion, and stir at 40 °C for 6-12 h to obtain pyridone-intercalated CoMn-LDH. In the eighth step, the pyridone intercalated CoMn-LDH was washed twice with ultrapure water and freeze-dried for 12 h to obtain Pyr-CoMn-LDH.
[0007] Furthermore, the usage ratio of the cobalt nitrate hexahydrate, manganese chloride tetrahydrate and ultrapure water in the first step is 0.349 g: 0.119 g: 30 mL.
[0008] Furthermore, the dosage ratio of PVP and ultrapure water in the second step is 50-200 mg:10 mL.
[0009] Furthermore, the usage ratio of NaOH and ultrapure water in the third step is 0.35 g:40 mL.
[0010] Furthermore, in the seventh step, the usage ratio of CoMn-LDH, ultrapure water and pyridone is 4 mg: 2 mL: 2 mg.
[0011] The beneficial effects of the present invention are as follows: The present invention provides a method for preparing a pyridone intercalated cobalt-manganese hydrotalcite having the performance of singlet oxygen generation, storage and sustained release. The pyridone intercalated cobalt-manganese hydrotalcite can efficiently convert oxygen into singlet oxygen under 980 nm laser irradiation. The intercalated pyridone molecules have the performance of storage and sustained release. 1The function of O2 can realize the slow and continuous release of singlet oxygen, which makes up for the short life of singlet oxygen in traditional PDT preparations and has good application prospects in the field of PDT treatment. BRIEF DESCRIPTION OF THE DRAWINGS
[0012] Figure 1 This is a transmission electron micrograph of the pyridone intercalated cobalt-manganese hydrotalcite synthesized in Example 1 of the present invention and having the functions of singlet oxygen generation, storage and sustained release.
[0013] Figure 2 This is the X-ray diffraction pattern of the pyridone intercalated cobalt-manganese hydrotalcite with singlet oxygen generation, storage and sustained release functions synthesized in Example 1 of the present invention.
[0014] Figure 3 This is the singlet oxygen generation performance of the CoMn-LDH synthesized in Example 1 of the present invention.
[0015] Figure 4 This is the singlet oxygen sustained release performance of the pyridone intercalated cobalt-manganese hydrotalcite synthesized in Example 1 of the present invention. DETAILED DESCRIPTION
[0016] The technical solution of the present invention will be clearly and completely described below in combination with the embodiments of the present invention and the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0017] Example 1 A method for preparing pyridone intercalated cobalt-manganese hydrotalcite with singlet oxygen generation, storage and sustained release functions: At room temperature, weigh 0.349 g of cobalt nitrate hexahydrate and 0.119 g of manganese chloride tetrahydrate, add them to 30 mL of ultrapure water, and stir at 40 °C for 10 min to obtain a salt solution for use; Weigh 100 mg of PVP and add it to 55 mL of ultrapure water. Stir magnetically in a 40°C water bath until it is completely dissolved. While stirring, add the pre-prepared salt solution dropwise to the PVP solution and stir for 30 min to obtain a mixed salt solution. Weigh 0.35 g of sodium hydroxide and add it to 40 mL of ultrapure water. Stir at 45 °C for 10 min to obtain an alkaline solution. Under high-speed stirring at 65°C, the pre-prepared mixed salt solution was added dropwise to the alkaline solution until the pH value of the reaction system reached 12; After the addition was completed, the reaction temperature was maintained at 65°C and the hydrothermal reaction was carried out for 6 h.
[0018] After the reaction, the product was collected by centrifugation, washed with ultrapure water and ethanol, respectively, and dried at 60 °C for 6 h to obtain CoMn-LDH; Weigh 4 mg of CoMn-LDH and disperse it in 2 mL of ultrapure water. After ultrasonic dispersion for 5 min, add 2 mg of pyridone and stir at 40 °C for 6 h. Collect the product by centrifugation, wash twice with ultrapure water, and freeze-dry for 12 h to obtain Pyr-CoMn-LDH.
[0019] Example 2 A method for preparing pyridone intercalated cobalt-manganese hydrotalcite with singlet oxygen generation, storage and sustained release functions: At room temperature, weigh 0.349 g of cobalt nitrate hexahydrate and 0.119 g of manganese chloride tetrahydrate, add them to 30 mL of ultrapure water, and stir at 40 °C for 10 min to obtain a salt solution for use; Weigh 50 mg of PVP and add it to 55 mL of ultrapure water. Stir magnetically in a 40°C water bath until it is completely dissolved. While stirring, add the pre-prepared salt solution dropwise to the PVP solution and stir for 30 min to obtain a mixed salt solution. Weigh 0.35 g of sodium hydroxide and add it to 40 mL of ultrapure water. Stir at 45 °C for 10 min to obtain an alkaline solution. Under high-speed stirring at 65°C, the pre-prepared mixed salt solution was added dropwise to the alkaline solution until the pH value of the reaction system reached 12; After the dropwise addition was completed, the reaction temperature was maintained at 65° C. and the hydrothermal reaction was carried out for 3 h.
[0020] After the reaction, the product was collected by centrifugation, washed with ultrapure water and ethanol, respectively, and dried at 60 °C for 6 h to obtain CoMn-LDH; Weigh 4 mg of CoMn-LDH and disperse it in 2 mL of ultrapure water. After ultrasonic dispersion for 5 min, add 2 mg of pyridone and stir at 40 °C for 8 h. Collect the product by centrifugation, wash twice with ultrapure water, and freeze-dry for 12 h to obtain Pyr-CoMn-LDH.
[0021] Example 3 A method for preparing pyridone intercalated cobalt-manganese hydrotalcite with singlet oxygen generation, storage and sustained release functions: At room temperature, weigh 0.349 g of cobalt nitrate hexahydrate and 0.119 g of manganese chloride tetrahydrate, add them to 30 mL of ultrapure water, and stir at 40 °C for 10 min to obtain a salt solution for use; Weigh 100 mg of PVP and add it to 55 mL of ultrapure water. Stir magnetically in a 40°C water bath until it is completely dissolved. While stirring, add the pre-prepared salt solution dropwise to the PVP solution and stir for 30 min to obtain a mixed salt solution. Weigh 0.35 g of sodium hydroxide and add it to 40 mL of ultrapure water. Stir at 45 °C for 10 min to obtain an alkaline solution. Under high-speed stirring at 65°C, the pre-prepared mixed salt solution was added dropwise to the alkaline solution until the pH value of the reaction system reached 12; After the addition was completed, the reaction temperature was maintained at 65° C. and the hydrothermal reaction was carried out for 12 h.
[0022] After the reaction, the product was collected by centrifugation, washed with ultrapure water and ethanol, respectively, and dried at 60 °C for 6 h to obtain CoMn-LDH; Weigh 4 mg of CoMn-LDH and disperse it in 2 mL of ultrapure water. After ultrasonic dispersion for 5 min, add 2 mg of pyridone and stir at 40 °C for 6 h. Collect the product by centrifugation, wash twice with ultrapure water, and freeze-dry for 12 h to obtain Pyr-CoMn-LDH.
[0023] Example 4 A method for preparing pyridone intercalated cobalt-manganese hydrotalcite with singlet oxygen generation, storage and sustained release functions: At room temperature, weigh 0.349 g of cobalt nitrate hexahydrate and 0.119 g of manganese chloride tetrahydrate, add them to 30 mL of ultrapure water, and stir at 40 °C for 10 min to obtain a salt solution for use; Weigh 200 mg of PVP and add it to 55 mL of ultrapure water. Stir magnetically in a 40°C water bath until it is completely dissolved. While stirring, add the pre-prepared salt solution dropwise to the PVP solution and stir for 30 min to obtain a mixed salt solution. Weigh 0.35 g of sodium hydroxide and add it to 40 mL of ultrapure water. Stir at 45 °C for 10 min to obtain an alkaline solution. Under high-speed stirring at 65°C, the pre-prepared mixed salt solution was added dropwise to the alkaline solution until the pH value of the reaction system reached 12; After the addition was completed, the reaction temperature was maintained at 65° C. and the hydrothermal reaction was carried out for 6 hours.
[0024] After the reaction, the product was collected by centrifugation, washed with ultrapure water and ethanol, respectively, and dried at 60 °C for 6 h to obtain CoMn-LDH; Weigh 4 mg of CoMn-LDH and disperse it in 2 mL of ultrapure water. After ultrasonic dispersion for 5 min, add 2 mg of pyridone and stir at 40 °C for 12 h. Collect the product by centrifugation, wash twice with ultrapure water, and freeze-dry for 12 h to obtain Pyr-CoMn-LDH.
[0025] Example 5 A method for preparing pyridone intercalated cobalt-manganese hydrotalcite with singlet oxygen generation, storage and sustained release functions: At room temperature, weigh 0.349 g of cobalt nitrate hexahydrate and 0.119 g of manganese chloride tetrahydrate, add them to 30 mL of ultrapure water, and stir at 40 °C for 10 min to obtain a salt solution for use; Weigh 100 mg of PVP and add it to 55 mL of ultrapure water. Stir magnetically in a 40°C water bath until it is completely dissolved. While stirring, add the pre-prepared salt solution dropwise to the PVP solution and stir for 30 min to obtain a mixed salt solution. Weigh 0.35 g of sodium hydroxide and add it to 40 mL of ultrapure water. Stir at 45 °C for 10 min to obtain an alkaline solution. Under high-speed stirring at 65°C, the pre-prepared mixed salt solution was added dropwise to the alkaline solution until the pH value of the reaction system reached 12; After the addition was completed, the reaction temperature was maintained at 85° C. and the hydrothermal reaction was carried out for 6 hours.
[0026] After the reaction, the product was collected by centrifugation, washed with ultrapure water and ethanol, respectively, and dried at 60 °C for 6 h to obtain CoMn-LDH; Weigh 4 mg of CoMn-LDH and disperse it in 2 mL of ultrapure water. After ultrasonic dispersion for 5 min, add 2 mg of pyridone and stir at 40 °C for 6 h. Collect the product by centrifugation, wash twice with ultrapure water, and freeze-dry for 12 h to obtain Pyr-CoMn-LDH.
[0027] Example 6 A method for preparing pyridone intercalated cobalt-manganese hydrotalcite with singlet oxygen generation, storage and sustained release functions: At room temperature, weigh 0.349 g of cobalt nitrate hexahydrate and 0.119 g of manganese chloride tetrahydrate, add them to 30 mL of ultrapure water, and stir at 40 °C for 10 min to obtain a salt solution for use; Weigh 100 mg of PVP and add it to 55 mL of ultrapure water. Stir magnetically in a 40°C water bath until it is completely dissolved. While stirring, add the pre-prepared salt solution dropwise to the PVP solution and stir for 30 min to obtain a mixed salt solution. Weigh 0.35 g of sodium hydroxide and add it to 40 mL of ultrapure water. Stir at 45 °C for 10 min to obtain an alkaline solution. Under high-speed stirring at 65°C, the pre-prepared mixed salt solution was added dropwise to the alkaline solution until the pH value of the reaction system reached 12; After the dropwise addition was completed, the reaction temperature was maintained at 75° C. and the hydrothermal reaction was carried out for 6 hours.
[0028] After the reaction, the product was collected by centrifugation, washed with ultrapure water and ethanol, respectively, and dried at 60 °C for 6 h to obtain CoMn-LDH; Weigh 4 mg of CoMn-LDH and disperse it in 2 mL of ultrapure water. After ultrasonic dispersion for 5 min, add 2 mg of pyridone and stir at 40 °C for 12 h. Collect the product by centrifugation, wash twice with ultrapure water, and freeze-dry for 12 h to obtain Pyr-CoMn-LDH.
[0029] The DPBF probe was used to detect singlet oxygen in the pyridone intercalated cobalt-manganese hydrotalcite prepared by the present invention, and its singlet oxygen generation and release performance were evaluated.
[0030] Figure 1 This is a transmission electron microscope image of the pyridone intercalated cobalt manganese hydrotalcite with singlet oxygen generation, storage and sustained release functions synthesized in Example 1 of the present invention. It can be seen from the figure that the synthesized pyridone intercalated cobalt manganese hydrotalcite is a hexagonal thin layer structure with a size of about 120 nm.
[0031] Figure 2 This is the X-ray diffraction pattern of the pyridone intercalated cobalt manganese hydrotalcite with singlet oxygen generation, storage and sustained release functions synthesized in Example 1 of the present invention. The diffraction peaks of the pyridone intercalated cobalt manganese hydrotalcite at 19.5° and 36° match those of CoMn-LDH.
[0032] Figure 3 This is a singlet oxygen generation performance test diagram (DPBF probe) of the cobalt-manganese hydrotalcite synthesized in Example 1 of the present invention. It can be seen from the figure that the synthesized CoMn-LDH has a high efficiency in singlet oxygen generation capability, and DPBF is completely degraded in 14 min.
[0033] Figure 4 This is a singlet oxygen generation performance test diagram of the pyridone intercalated cobalt-manganese hydrotalcite synthesized in Example 1 of the present invention, combined with Figure 3 As a result, the cobalt-manganese hydrotalcite intercalated with pyridone can store and slowly release the generated singlet oxygen, and the sustained release time of singlet oxygen reaches 3 h.
[0034] Only the preferred embodiments of the present invention are described in detail above, but the present invention is not limited to the above embodiments. Various changes can be made within the knowledge scope of ordinary technicians in this field without departing from the purpose of the present invention, and various changes should be included in the protection scope of the present invention.
Claims
1. A pyridone intercalated cobalt-manganese hydrotalcite with singlet oxygen generation, storage and sustained release functions, characterized in that: The intercalated hydrotalcite is a thin layer of CoMn-LDH, and pyridone molecules are assembled between the layers to obtain pyridone intercalated cobalt-manganese hydrotalcite Pyr-CoMn-LDH, wherein the structure of the pyridone intercalated cobalt-manganese hydrotalcite is a hexagonal thin layer; The pyridone intercalated cobalt manganese hydrotalcite efficiently converts oxygen into singlet oxygen under 980 nm laser irradiation, and the intercalated pyridone molecules act as "singlet oxygen reservoirs" to quickly and efficiently capture and slowly release singlet oxygen through a reversible Diels-Alder reaction.
2. A method for preparing the pyridone intercalated cobalt-manganese hydrotalcite with singlet oxygen generation, storage and sustained release functions as claimed in claim 1, characterized in that: The steps include: In the first step, cobalt nitrate hexahydrate and manganese chloride tetrahydrate were added to ultrapure water and stirred at 40°C for 10 min to obtain a salt solution; In the second step, PVP was added to ultrapure water and magnetically stirred in a 40°C water bath until completely dissolved. Under stirring, the salt solution was added dropwise to the PVP solution and stirring was continued for 30 min to obtain a mixed salt solution. In the third step, NaOH was dissolved in ultrapure water and stirred at 40 °C for 10 min to obtain an alkaline solution; Step 4: adding the mixed salt solution dropwise into the alkaline solution under 65°C conditions and ultrasonic dispersion stirring at a frequency of 50 kHz until the pH value of the solution reaches 12; Step 5: After the addition is completed, the reaction temperature is maintained at 65-85°C and the hydrothermal reaction is carried out for 3-12 hours; Step 6: After the reaction is completed, the product is collected by centrifugation, washed with ultrapure water and ethanol respectively, and dried in an electric blast drying oven at 60°C for 6 h to obtain CoMn-LDH; Step 7: Disperse CoMn-LDH in ultrapure water, perform ultrasonic dispersion for 5 min, add pyridone to the dispersion, and stir at 40 °C for 6-12 h to obtain pyridone-intercalated CoMn-LDH. In the eighth step, the pyridone intercalated CoMn-LDH was washed twice with ultrapure water and freeze-dried for 12 h to obtain Pyr-CoMn-LDH.
3. The method for preparing a pyridone intercalated cobalt-manganese hydrotalcite having singlet oxygen generation, storage and sustained release functions according to claim 2, characterized in that: The usage ratio of the cobalt nitrate hexahydrate, manganese chloride tetrahydrate and ultrapure water in the first step is 0.349 g:0.119 g:30 mL.
4. The method for preparing a pyridone intercalated cobalt-manganese hydrotalcite having singlet oxygen generation, storage and sustained release functions according to claim 2, characterized in that: The dosage ratio of PVP and ultrapure water in the second step is 50-200 mg:10 mL.
5. The method for preparing a pyridone intercalated cobalt-manganese hydrotalcite having singlet oxygen generation, storage and sustained release functions according to claim 2, characterized in that: The usage ratio of NaOH and ultrapure water in the third step is 0.35 g:40 mL.
6. The method for preparing a pyridone intercalated cobalt-manganese hydrotalcite having singlet oxygen generation, storage and sustained release functions according to claim 2, characterized in that: The usage ratio of CoMn-LDH, ultrapure water and pyridone in the seventh step is 4 mg: 2 mL: 2 mg.