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A preparation method of near-infrared responsive nanocages and its application in combined tumor immunotherapy

A nano-cage, near-infrared technology, applied in the medical field, can solve problems such as limiting the clinical benefit of patients, and achieve the effects of uniform and controllable mesopore size, large specific surface area and pore volume, and excellent biocompatibility.

Active Publication Date: 2022-07-08
WEST CHINA HOSPITAL SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are a large number of clinical (pre) studies of this combination regimen, but the combination therapy is only effective in some patients, which seriously limits the clinical benefits of patients

Method used

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  • A preparation method of near-infrared responsive nanocages and its application in combined tumor immunotherapy
  • A preparation method of near-infrared responsive nanocages and its application in combined tumor immunotherapy
  • A preparation method of near-infrared responsive nanocages and its application in combined tumor immunotherapy

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Embodiment 1

[0063] The present embodiment provides a method for preparing a near-infrared responsive nanocage, comprising the following steps:

[0064] (1) prepare gold nanocages (AuNC), the method is as follows:

[0065] (S1) 500 μL of Ag nanocubes with a concentration of 3 nmol / L were added to 5 mL of a polyvinylpyrrolidone (PVP) ion aqueous solution with a concentration of 1 mg / mL, then heated and boiled for 10 min, and continuously stirred to obtain mixture a;

[0066] (S2) take 0.5mmol HAuCl 4 The aqueous solution was added to mixture a at a rate of 45 mL / h, and the system was refluxed for 30 min until the color was stable, and then cooled to room temperature to obtain mixture b;

[0067] (S3) Centrifuge the mixture b, first remove AgCl with saturated NaCl solution, and then wash with deionized water to remove residual PVP and NaCl to obtain AuNC.

[0068] (II) Preparation of mesoporous silica-coated gold nanocages (AuNC@mSiO 2 ),Methods as below:

[0069] (SS1) 4 mL of AuNC obtain...

Embodiment 2

[0080] This embodiment provides a method for preparing a near-infrared responsive nanocages, which is different from Embodiment 1 in that: in step (S1), the heating and boiling time is 15 min; in step (S2), HAuCl 4 The addition rate of the aqueous solution was 50 mL / h, and the time for continuous reflux was 40 min; in step (SS1), the reaction was continuously stirred for 14 h at room temperature; in step (SS2), the centrifugation was performed at 7000 g for 20 min; The washing is performed alternately with ethanol and deionized water for 4 times; the stirring reaction is carried out at 55°C for 12 hours; in step (SSS2), the heating reaction is carried out at 90°C for 8 hours; the centrifugation is carried out at 7000g Centrifuge for 15 min; in step (SSS3), the heating is at 75° C. and the reaction time is 5 h; in step (SSSS2), the heating is at 45° C. and the reaction time is 28 h.

[0081] Other operations and the amount of raw materials are the same as in Example 1.

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Abstract

The invention relates to a preparation method of a near-infrared responsive nano-cage and its application in combined tumor immunotherapy. The preparation method of the near-infrared responsive nanocages includes preparing AuNC, preparing AuNC@mSiO 2 , prepare ASP and prepare ASP∩V four steps. The near-infrared responsive nanocages have the advantages of good biocompatibility, safety, photothermal conversion in the near-infrared region, and high drug loading capacity. Drug-loaded nanocages can effectively deliver drugs into tumor cells and convert light energy into heat energy. Photothermal combined with BRAF inhibitors inhibits tumor growth, induces immunogenic necrosis of tumor cells, and promotes the release of tumor-associated antigens, producing a system Anti-PD-1 antibody synergistically inhibits tumor growth. The gold nanocages realize MAPK molecular targeting and anti-PD-1 immunotherapy combined, providing a new strategy for tumor treatment.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a preparation method of a near-infrared responsive nano-cage and its application in combined tumor immunotherapy. Background technique [0002] In recent years, with the deepening of tumor immune escape mechanism research, immunotherapy especially targets programmed cell death 1 (PD-1) and its ligand (programed cell death-ligand1, PD-L1) as immune checkpoints. Inhibitors significantly prolong patient survival in a variety of tumors. However, PD-1 / PD-L1 immunotherapy still has a severe clinical bottleneck, that is, the response rate of monotherapy is only 10%-40%. The reason is that PD-1 / PD-L1 immune checkpoint blockade is dependent on CD8 in the tumor microenvironment + T cells, while most patients lack immune cells in the tumor microenvironment, known as immune "cold" tumors. In order to solve this problem, a large number of explorations of combined therapy with anti-PD-1 ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K47/02A61K47/69A61K31/437A61P35/00B22F1/054B22F1/16B22F9/24B82Y5/00B82Y40/00
CPCA61K41/0052A61K41/0042A61K31/437A61K47/6949A61P35/00B82Y5/00B22F9/24B82Y40/00B22F1/0553B22F1/054B22F1/16A61K2300/00
Inventor 刘小伟
Owner WEST CHINA HOSPITAL SICHUAN UNIV
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