SELENIUM-DOPED BLACK PHOSPHORUS PRODRUG AND PREPARATION METHOD THEREFOR

Abstract

Disclosed is a selenium-doped black phosphorus prodrug comprising selenium-doped black phosphorus nanosheets and polyethylene glycol amine coating the surface of the selenium-doped black phosphorus nanosheets. The selenium-doped black phosphorus nanosheets comprise black phosphorus nanosheets and selenium elements doped in the black phosphorus nanosheets, with the selenium elements replacing positions of a portion of the phosphorus atoms in the black phosphorus crystal lattice. The selenium-doped black phosphorus prodrug is a controlled-release prodrug of selenium elements, which can realize the near-infrared light controlled-release of selenium elements, thereby controllably regulating selenium content in the human body, regulating human immunity, and preventing and treating cancers. Also provided is a method for preparing the selenium-doped black phosphorus prodrug.

Claims

1. A selenium-doped black phosphorus prodrug comprising: selenium-doped black phosphorus nanosheets, and polyethylene glycol amine coated on the surface of the selenium-doped black phosphorus nanosheets, wherein the selenium-doped black phosphorus nanosheets comprises black phosphorus nanosheets and selenium doped in the black phosphorus nanosheets, and wherein the selenium replaces a part of phosphorus atoms in the black phosphorus crystal lattice.

2. The selenium-doped black phosphorus prodrug of claim 1, wherein the selenium is doped in the selenium-doped black phosphorus nanosheets at a mass concentration of 0.1-5%.

3. The selenium-doped black phosphorus prodrug of claim 2, wherein the selenium is doped in the selenium-doped black phosphorus nanosheets at a mass concentration of 2-5%.

4. The selenium-doped black phosphorus prodrug of claim 2, wherein the selenium is doped in the selenium-doped black phosphorus nanosheets at a mass concentration of 1-4%.

5. The selenium-doped black phosphorus prodrug of claim 1, wherein length and width dimensions of the selenium-doped black phosphorus nanosheets are in a range of 50 nm-200 nm.

6. The selenium-doped black phosphorus prodrug of claim 5, wherein length and width dimensions of the selenium-doped black phosphorus nanosheets are in a range of 100 nm-200 nm.

7. The selenium-doped black phosphorus prodrug of claim 1, wherein thickness of the selenium-doped black phosphorus nanosheets is in a range of 1 nm-5 nm.

8. The selenium-doped black phosphorus prodrug of claim 1, wherein mass ratio of the selenium-doped black phosphorus nanosheets to the polyethylene glycol amine is in a range of 1:(0.2-10).

9. The selenium-doped black phosphorus prodrug of claim 1, wherein the polyethylene glycol amine is adsorbed on the surface of the selenium-doped black phosphorus nanosheets due to electrostatic force, and wherein weight average molecular weight of polyethylene glycol amine is in a range of 2000-30000.

10. The selenium-doped black phosphorus prodrug of claim 1, wherein the polyethylene glycol amine comprises at least one compound selected from the group consisting of methyl polyethylene glycol amine, methoxy polyethylene glycol amine and polyethylene glycol diamine.

11. A method for preparing a selenium-doped black phosphorus prodrug, comprising: sealing red phosphorus, tin, tin tetraiodide and selenium in a silicon glass vacuum tube at a mass ratio of (200-500):(10-20):(5-10):(0.5-10); placing the silicon glass vacuum tube horizontally in a heating furnace, followed by heating the silicon glass vacuum to 700-800 C. and maintaining for 1-5 hours, and then cooling to 450-550 C. and maintaining for 5-9 hours, and then further cooling to 100-200 C. and maintaining for 6-10 hours, followed by cooling to room temperature to obtain selenium-doped black phosphorus crystals in the silicon glass vacuum tube; dispersing the selenium-doped black phosphorus crystals into an aqueous phase by liquid exfoliation to obtain suspended selenium-doped black phosphorus nanosheets; coating the selenium-doped black phosphorus nanosheets with polyethylene glycol amine while ultrasonicating and stirring to obtain a selenium-doped black phosphorus prodrug, which comprises: selenium-doped black phosphorus nanosheets, and polyethylene glycol amine coated on the surface of the selenium-doped black phosphorus nanosheets, wherein the selenium-doped black phosphorus nanosheets comprises black phosphorus nanosheets and selenium doped in the black phosphorus nanosheets, and wherein the selenium replaces a part of phosphorus atoms in the black phosphorus crystal lattice.

12. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein the step of heating is performed at a heating rate of 1-5 C./min.

13. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein the step of cooling to 450-550 C. is performed at a cooling rate of 1-3 C./min.

14. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein the step of cooling to 100-200 C. is performed at a cooling rate of 1-3 C./min.

15. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein mass ratio of the selenium-doped black phosphorus nanosheets to polyethylene glycol amine is in a range of 1:(0.2-10).

16. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein weight average molecular weight of polyethylene glycol amine is in a range of 2000-30000.

17. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein the polyethylene glycol amine comprises at least one compound selected from the group consisting of methyl polyethylene glycol amine, methoxy polyethylene glycol amine and polyethylene glycol diamine.

18. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein mass of the selenium is 0.1-5% of mass of the red phosphorus.

19. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein mass of the tin is 2-10% of mass of the red phosphorus.

20. The method for preparing a selenium-doped black phosphorus prodrug of claim 11, wherein the ultrasonic treatment uses an ultrasonic frequency of 3000-4500 HZ and lasts for 0.5-2 hours, and the step of stirring is performed at a speed of 800 rpm-1200 rpm for 2-4 hours.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0033] FIG. 1 shows structure of a selenium-doped black phosphorus prodrug prepared in Example 1 of the present invention.

[0034] FIG. 2 shows a photo of selenium-doped black phosphorus crystals prepared at step (2) of Example 1 of the present invention.

[0035] FIG. 3 shows a Raman spectrum of selenium-doped black phosphorus crystals prepared at step (2) of Example 1 of the present invention.

[0036] FIG. 4 shows an ultraviolet-visible absorption spectrum of the selenium-doped black phosphorus crystals prepared at step (2) of Example 1 of the present invention.

[0037] FIG. 5 shows a transmission electron microscope (SEM) image of a selenium-doped black phosphorus prodrug prepared in Example 1 of the present invention.

[0038] FIG. 6 shows release and degradation of a selenium-doped black phosphorus prodrug prepared according to one embodiment of the present invention.

[0039] FIG. 7 shows a transmission electron microscope (SEM) image of a selenium-doped black phosphorus prodrug prepared in Example 2 of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[0040] The following describes preferred embodiments of the present invention. It should be noted that those skilled in the art can make several improvements or modifications without departing from the principles of the embodiments of the present invention. These improvements or modification are also considered as the protection scope of the present invention.

EXAMPLE 1

[0041] A method for preparing selenium-doped black phosphorus prodrug comprises the following steps.

[0042] (1) 500 mg of red phosphorus, 20 mg of tin, 10 mg of tin tetraiodide and 0.5 mg of selenium were sealed in a silicon glass vacuum tube.

[0043] (2) The silicon glass tube was placed horizontally in a heating furnace and heated at a heating rate of 3 C./min to 750 C. and maintained for 1 hour, and then cooled at a cooling rate of 3 C./min to 500 C. and maintained for 7.5 hours. Further, the glass tube was cooled at a cooling rate of 3 C./min to 150 C. and maintained for 8 hours, and then cooled to room temperature to obtain selenium-doped black phosphorus crystals deposited on the end of the silicon glass tube.

[0044] (3) The selenium-doped black phosphorus crystals were dispersed in the aqueous phase by liquid exfoliation to obtain suspended selenium-doped black phosphorus nanosheets, which were then coated with polyethylene glycol amine sequentially by ultrasonicating and stirring so as to obtain the selenium-doped black phosphorus prodrug, wherein the mass ratio of selenium-doped black phosphorus nanosheets to polyethylene glycol amine was 1:2. The ultrasonic treatment was performed at a frequency of 4000 HZ for 2 hours, and the magnetic stirring was performed at a speed of 800 rpm for 4 hours.

[0045] FIG. 1 shows structure of a selenium-doped black phosphorus prodrug prepared in Example 1 of the present invention. The prodrug comprises selenium-doped black phosphorus nanosheets 10 and polyethylene glycol amine 11 coated on the surface of the selenium-doped black phosphorus nanosheets, wherein the selenium-doped black phosphorus nanosheets 10 comprises black phosphorus nanosheets and selenium 12 doped in the black phosphorus nanosheets, and wherein the selenium 12 replaces a part of phosphorus atoms in the black phosphorus crystal lattice.

[0046] FIG. 2 shows a photo of selenium-doped black phosphorus crystals prepared at step (2) of Example 1 of the present invention. FIG. 3 and FIG. 4 show a Raman spectrum and an ultraviolet-visible absorption spectrum of the selenium-doped black phosphorus crystals prepared at step (2) of Example 1 of the present invention. In FIG. 3, curve 1 is the Raman spectrum of black phosphorus crystals without selenium. Curves 2, 3, and 4 are the Raman spectra of black phosphorus crystals doping with 0.3%, 2%, and 5% of selenium, respectively. It can be seen from FIG. 3 that new Raman peaks of selenium appear in curves 2, 3, and 4, indicating that the selenium is successfully doped. In FIG. 4, curve 1 is an ultraviolet-visible absorption spectrum of black phosphorus crystals without selenium. Curves 2 and 3 are ultraviolet-visible absorption spectrum of black phosphorus crystals doping with 2% and 5% of selenium, respectively. It can be seen from FIG. 4 that the absorption spectrum undergoes a significant red shift with increasing selenium content, thereby improving the near-infrared response of selenium-doped black phosphorus crystals, which is beneficial to the controlled-release drugs for deep tissues.

[0047] FIG. 5 shows a transmission electron microscope (SEM) image of a selenium-doped black phosphorus prodrug prepared in Example 1 of the present invention. The size of the selenium-doped black phosphorus prodrug is in a range of 100-200 nm.

[0048] The selenium-doped black phosphorus prodrug prepared according to the embodiment of the present invention under the near-infrared irradiation at 808 nm, on the one hand, would exhibit excellent light-to-heat conversion due to the black phosphorus nanosheets per se, so as to realize photothermal treatment. On the other hand, the selenium-doped black phosphorus nanosheets can be degraded under near-infrared irradiation. During the degradation, phosphorus atoms are oxidized to non-toxic compounds such as phosphoric acid, and selenium atoms are oxidized to selenite ions and release gradually. Selenite has anti-cancer properties and improves immunity, so that the selenium-doped black phosphorus prodrug prepared according to the embodiment of the present invention can effectively inhibit the growth of cancer cells. Since black phosphorus nanosheets have good biocompatibility and can be excreted through biodegradation or normal physiological pathways, the selenium-doped black phosphorus prodrugs prepared in the embodiments of the present invention have no toxic side effects on the organism with biological safety. FIG. 6 shows release and degradation of a selenium-doped black phosphorus prodrug prepared according to one embodiment of the present invention.

EXAMPLE 2

[0049] A method for preparing selenium-doped black phosphorus prodrug comprises the following steps.

[0050] (1) 500 mg of red phosphorus, 20 mg of tin, 10 mg of tin tetraiodide and 2.5 mg of selenium were sealed in a silicon glass vacuum tube.

[0051] (2) The silicon glass tube was placed horizontally in a heating furnace and heated at a heating rate of 4 C./min to 800 C. and maintained for 3 hours, and then cooled at a cooling rate of 2 C./min to 550 C. and maintained for 6 hours. Further, the glass tube was cooled at a cooling rate of 2 C./min to 100 C. and maintained for 8 hours, and then cooled to room temperature to obtain selenium-doped black phosphorus crystals deposited on the end of the silicon glass tube.

[0052] (3) The selenium-doped black phosphorus crystals were dispersed in the aqueous phase by liquid exfoliation to obtain suspended selenium-doped black phosphorus nanosheets, which were then coated with polyethylene glycol amine sequentially by ultrasonicating and stirring so as to obtain the selenium-doped black phosphorus prodrug, wherein the mass ratio of selenium-doped black phosphorus nanosheets to polyethylene glycol amine was 1:4. The ultrasonic treatment was performed at a frequency of 4500 HZ for 2 hours, and the magnetic stirring was performed at a speed of 1000 rpm for 4 hours.

[0053] FIG. 7 shows a transmission electron microscope (SEM) image of a selenium-doped black phosphorus prodrug prepared in Example 2 of the present invention. The size of the selenium-doped black phosphorus prodrug is in a range of 50-100 nm.

EXAMPLE 3

[0054] A method for preparing selenium-doped black phosphorus prodrug comprises the following steps.

[0055] (1) 500 mg of red phosphorus, 20 mg of tin, 10 mg of tin tetraiodide and 5 mg of selenium were sealed in a silicon glass vacuum tube.

[0056] (2) The silicon glass tube was placed horizontally in a heating furnace and heated at a heating rate of 1 C./min to 800 C. and maintained for 4 hours, and then cooled at a cooling rate of 1 C./m in to 500 C. and maintained for 8 hours. Further, the glass tube was cooled at a cooling rate of 1 C./min to 150 C. and maintained for 7 hours, and then cooled to room temperature to obtain selenium-doped black phosphorus crystals deposited on the end of the silicon glass tube.

[0057] (3) The selenium-doped black phosphorus crystals were dispersed in the aqueous phase by liquid exfoliation to obtain suspended selenium-doped black phosphorus nanosheets, which were then coated with polyethylene glycol amine sequentially by ultrasonicating and stirring so as to obtain the selenium-doped black phosphorus prodrug, wherein the mass ratio of selenium-doped black phosphorus nanosheets to polyethylene glycol amine was 1:2. The ultrasonic treatment was performed at a frequency of 3500 HZ for 2 hours, and the magnetic stirring was performed at a speed of 800 rpm for 4 hours.

EXAMPLE 4

[0058] A method for preparing selenium-doped black phosphorus prodrug comprises the following steps.

[0059] (1) 500 mg of red phosphorus, 20 mg of tin, 10 mg of tin tetraiodide and 10 mg of selenium were sealed in a silicon glass vacuum tube.

[0060] (2) The silicon glass tube was placed horizontally in a heating furnace and heated at a heating rate of 5 C./min to 850 C. and maintained for 4 hours, and then cooled at a cooling rate of 3 C./min to 550 C. and maintained for 6 hours. Further, the glass tube was cooled at a cooling rate of 3 C./min to 150 C. and maintained for 10 hours, and then cooled to room temperature to obtain selenium-doped black phosphorus crystals deposited on the end of the silicon glass tube.

[0061] (3) The selenium-doped black phosphorus crystals were dispersed in the aqueous phase by liquid exfoliation to obtain suspended selenium-doped black phosphorus nanosheets, which were then coated with polyethylene glycol amine sequentially by ultrasonicating and stirring so as to obtain the selenium-doped black phosphorus prodrug, wherein the mass ratio of selenium-doped black phosphorus nanosheets to polyethylene glycol amine was 1:2. The ultrasonic treatment was performed at a frequency of 3000 HZ for 2 hours, and the magnetic stirring was performed at a speed of 1200 rpm for 3 hours.

[0062] It should be noted that the foregoing descriptions are merely specific embodiments of the present invention, but are not intended to limit the protection scope of the present invention. Any variation or replacement readily figured out by a person skilled in the art within the technical scope disclosed in the present invention shall fall within the protection scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.