Antibody coupling bismuth selenide nanometer particles for united treatment of tumor thermal treatment and immunotherapy and preparation method of antibody coupling bismuth selenide nanometer particles

Abstract

The invention relates to antibody coupling bismuth selenide nanometer particles for united treatment of tumor thermal treatment and immunotherapy and a preparation method of the antibody coupling bismuth selenide nanometer particles, and belongs to the field of a pharmaceutical preparation. According to the antibody coupling bismuth selenide nanometer particles, amination bismuth selenide is usedas a carrier, PEG is used as a cross-linking agent, and a CD47 resisting antibody is coupled to the surfaces of the nanometer particles. After an antibody coupling bismuth selenide nanometer particlesuspension is intravenously injected, the nanometer particles can be massively gathered to a tumor part in a targetted manner through an EPR effect, and the condition that drug administration of the CD47 resisting antibody to whole bodies of causes anemia, is avoided. Besides, the surface-modified CD47 resisting antibody and tumor cell surfaces are high-expressed CD47 molecule specific recognition, and CD47 and SIRP alpha signal channels are closed, so that macrophages anew obtain the capacity for swallowing tumor cells. Particularly, tumor cells are subjected to thermal treatment, the residual tumor cells are eliminated by the macrophages because a signal channel free from drug administration is closed, and the purpose of thoroughly eradicating rumors is realized. The method is reasonablein design, and simple in preparation technology, has broad application prospects, and lays a foundation for design and development of a corresponding drug administration system.

Description

technical field

[0001] The invention belongs to the field of pharmaceutical preparations, and relates to an antibody-coupled bismuth selenide nanoparticle used for tumor photothermal therapy combined with immunotherapy and a preparation method thereof, in particular to a photothermal treatment of tumors by using near-infrared laser and anti-CD47 antibody Bismuth selenide nanoparticles for treatment combined with immunotherapy and a preparation method thereof. technical background

[0002] Over the past few hundred years, cancer has been one of the diseases that seriously threaten human health and life. According to relevant data, the mortality rate of malignant tumors among Chinese residents has increased by 83.1% compared with the mid-1970s. Currently, there are three main methods of treatment for tumors, including surgical resection, radiation therapy, and chemotherapy. However, the above methods will cause collateral damage and severe toxicity to normal tissues, and the...

Examples

preparation example Construction

[0040] A method for preparing antibody-coupled bismuth selenide nanoparticles for photothermal therapy of tumors combined with immunotherapy, comprising the following steps:

[0041] In the first step, bismuth selenide nanoparticles (Bi 2 Se 3 )

[0042] 1.1) Accurately weigh 365mg of Bi(NO 3 ) 3 ·5H 2 O dissolved in 10mL 1mol / L NHO 3 solution and placed in a 100mL small beaker, then add 106mg of NaOH to the mixed solution to obtain a mixed solution. Add 1.2 g of polyvinylpyrrolidone (PVP) to 50 mL of ethylene glycol (EG) on a magnetic stirrer while stirring at a power of 1200 r / min, and then ultrasonicate the mixed solution for 5 min. Finally, the above two reaction solutions were mixed and transferred to a high-pressure reactor, and heated at 150° C. for 3 hours. The obtained reaction solution was washed three times with deionized water, and then dissolved in 10 mL of deionized water again for subsequent reaction.

[0043] 1.2) Mix 10mL of bismuth oxide solution with...

Embodiment 2

[0067] A method for preparing antibody-coupled bismuth selenide nanoparticles for photothermal therapy of tumors combined with immunotherapy, comprising the following steps:

[0068] In the first step, bismuth selenide nanoparticles (Bi 2 Se 3 )

[0069] 1.1) Accurately weigh 182mg of Bi(NO 3 ) 3 ·5H 2 O dissolved in 5 mL of 1mol / L NHO 3 solution and placed in a 100mL small beaker, then 80mg of NaOH was added to the mixed solution to obtain a mixed solution. Add 0.8 g of polyvinylpyrrolidone (PVP) to 25 mL of ethylene glycol (EG) on a magnetic stirrer while stirring at a power of 1500 r / min, and then ultrasonicate the mixed solution for 5 min. Finally, the above two reaction solutions were mixed and transferred to a high-pressure reactor, and heated at 130° C. for 3 hours. The obtained reaction solution was washed three times with deionized water, and dissolved in 5 mL of deionized water again for subsequent reaction.

[0070] 1.2) Mix 5mL of bismuth oxide solution wit...

Embodiment 3

[0080] A method for preparing antibody-coupled bismuth selenide nanoparticles for photothermal therapy of tumors combined with immunotherapy, comprising the following steps:

[0081] In the first step, bismuth selenide nanoparticles (Bi 2 Se 3 )

[0082] 1.1) Accurately weigh 728mg of Bi(NO 3 ) 3 ·5H 2 O dissolved in 20mL 1mol / L NHO 3 solution and placed in a 100mL small beaker, then add 320mg of NaOH to the mixed solution to obtain a mixed solution. 100mL of ethylene glycol (EG) was placed on a magnetic stirrer with stirring at a power of 1500r / min, and 1.8g of polyvinylpyrrolidone (PVP) was added, and then the mixed solution was sonicated for 5min. Finally, the above two reaction solutions were mixed and transferred to a high-pressure reactor, and heated at 180° C. for 5 hours. The obtained reaction solution was washed three times with deionized water, and dissolved in 20 mL of deionized water again for subsequent reaction.

[0083] 1.2) Mix 20mL of bismuth oxide sol...

technical field

[0001] The invention belongs to the field of pharmaceutical preparations, and relates to an antibody-coupled bismuth selenide nanoparticle used for tumor photothermal therapy combined with immunotherapy and a preparation method thereof, in particular to a photothermal treatment of tumors by using near-infrared laser and anti-CD47 antibody Bismuth selenide nanoparticles for treatment combined with immunotherapy and a preparation method thereof. technical background

[0002] Over the past few hundred years, cancer has been one of the diseases that seriously threaten human health and life. According to relevant data, the mortality rate of malignant tumors among Chinese residents has increased by 83.1% compared with the mid-1970s. Currently, there are three main methods of treatment for tumors, including surgical resection, radiation therapy, and chemotherapy. However, the above methods will cause collateral damage and severe toxicity to normal tissues, and the...

Examples

preparation example Construction

[0040] A method for preparing antibody-coupled bismuth selenide nanoparticles for photothermal therapy of tumors combined with immunotherapy, comprising the following steps:

[0041] In the first step, bismuth selenide nanoparticles (Bi 2 Se 3 )

[0042] 1.1) Accurately weigh 365mg of Bi(NO 3 ) 3 ·5H 2 O dissolved in 10mL 1mol / L NHO 3 solution and placed in a 100mL small beaker, then add 106mg of NaOH to the mixed solution to obtain a mixed solution. Add 1.2 g of polyvinylpyrrolidone (PVP) to 50 mL of ethylene glycol (EG) on a magnetic stirrer while stirring at a power of 1200 r / min, and then ultrasonicate the mixed solution for 5 min. Finally, the above two reaction solutions were mixed and transferred to a high-pressure reactor, and heated at 150° C. for 3 hours. The obtained reaction solution was washed three times with deionized water, and then dissolved in 10 mL of deionized water again for subsequent reaction.

[0043] 1.2) Mix 10mL of bismuth oxide solution with...

Embodiment 2

[0067] A method for preparing antibody-coupled bismuth selenide nanoparticles for photothermal therapy of tumors combined with immunotherapy, comprising the following steps:

[0068] In the first step, bismuth selenide nanoparticles (Bi 2 Se 3 )

[0069] 1.1) Accurately weigh 182mg of Bi(NO 3 ) 3 ·5H 2 O dissolved in 5 mL of 1mol / L NHO 3 solution and placed in a 100mL small beaker, then 80mg of NaOH was added to the mixed solution to obtain a mixed solution. Add 0.8 g of polyvinylpyrrolidone (PVP) to 25 mL of ethylene glycol (EG) on a magnetic stirrer while stirring at a power of 1500 r / min, and then ultrasonicate the mixed solution for 5 min. Finally, the above two reaction solutions were mixed and transferred to a high-pressure reactor, and heated at 130° C. for 3 hours. The obtained reaction solution was washed three times with deionized water, and dissolved in 5 mL of deionized water again for subsequent reaction.

[0070] 1.2) Mix 5mL of bismuth oxide solution wit...

Embodiment 3

[0080] A method for preparing antibody-coupled bismuth selenide nanoparticles for photothermal therapy of tumors combined with immunotherapy, comprising the following steps:

[0081] In the first step, bismuth selenide nanoparticles (Bi 2 Se 3 )

[0082] 1.1) Accurately weigh 728mg of Bi(NO 3 ) 3 ·5H 2 O dissolved in 20mL 1mol / L NHO 3 solution and placed in a 100mL small beaker, then add 320mg of NaOH to the mixed solution to obtain a mixed solution. 100mL of ethylene glycol (EG) was placed on a magnetic stirrer with stirring at a power of 1500r / min, and 1.8g of polyvinylpyrrolidone (PVP) was added, and then the mixed solution was sonicated for 5min. Finally, the above two reaction solutions were mixed and transferred to a high-pressure reactor, and heated at 180° C. for 5 hours. The obtained reaction solution was washed three times with deionized water, and dissolved in 20 mL of deionized water again for subsequent reaction.

[0083] 1.2) Mix 20mL of bismuth oxide sol...

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