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Preparation method and application of NK cell co-stimulatory polymer micelles

A technology of co-stimulation and NK cells, applied in the field of biomedicine, can solve the problems of short biological half-life, capillary leakage, etc., and achieve the effects of promoting apoptosis, increasing particle size, and reducing glomerular filtration rate

Active Publication Date: 2022-03-15
NORTHWESTERN POLYTECHNICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, due to the short biological half-life of free cytokines such as IL-2 in clinical applications, high-dose injections need to be injected into patients for a long time, which will cause severe capillary leakage and other toxic side effects

Method used

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  • Preparation method and application of NK cell co-stimulatory polymer micelles
  • Preparation method and application of NK cell co-stimulatory polymer micelles
  • Preparation method and application of NK cell co-stimulatory polymer micelles

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Add 260 μl 200,000 U / ml IL-2 and 520 μl 200,000 U / ml IL-15 to the aqueous solution, then add TCEP (0.018 μmol, Beijing Yinuokai Technology Co., Ltd.), and stir the reaction at room temperature for 30- 40min;

[0062] Then add 0.6 mg of DBM-PEG-PTMC to the solution, and continue to stir and react at room temperature for 1 hour; Change the dialysis water every 4 hours);

[0063] After the dialysis, the sample was collected, centrifuged at 2000rpm / min (1000-2000rpm / min) for 10min (5-20min), the flocculent precipitate in the lower layer was discarded, the supernatant was collected, and concentrated by ultrafiltration with a 30KD ultrafiltration tube to obtain PEG-PTMC- IL-2 / IL-15 co-stimulatory polymer micelles.

[0064] The specific process parameters can be adjusted within the above range.

Embodiment 2

[0065] Embodiment 2: Inventive synthetic mechanism sees figure 1

[0066] This embodiment is different from Example 1 in that the DBM-PEG-PTMC used is synthesized by the following method:

[0067] 1) Diblock copolymer N 3 -Synthesis of PEG-PTMC: N 3 -PEG-OH (0.18mmol, 900mg, TCI (Shanghai) Chemical Industry Development Co., Ltd.), TMC (6.3mmol, 643.14mg, TCI (Shanghai) Chemical Industry Development Co., Ltd.) was dissolved in 5mL DMF, and then Add catalyst TBD (0.09mmol, 12.51mg, TCI (Shanghai) Chemical Industry Development Co., Ltd.) to the solution to initiate polymerization, and stir the reaction at room temperature for about 24h; after the reaction is completed, the reaction solution is rotated to remove some DMF, then the mixture was precipitated twice in glacial ether, and the precipitate was dried in a vacuum oven at room temperature to obtain a white solid product N 3 -PEG-PTMC;

[0068] 2) Synthesis of alkynyl-DBM: anhydrous potassium carbonate (1.79g, 12.9mmol),...

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Abstract

The invention discloses a preparation method and application of NK cell co-stimulatory polymer micelles. IL-15 and IL-2 are simultaneously loaded with PEG-PTMC polymers to prepare NK cell co-stimulatory polymer micelles (PEG-PTMC-IL ‑2 / IL‑15), has a high tumor inhibition rate, and can effectively promote the apoptosis of tumor cells.

Description

technical field [0001] The invention belongs to the technical field of biomedicine, and in particular relates to a preparation method and application of NK cell co-stimulatory polymer micelles. Background technique [0002] Cancer is one of the major diseases that seriously affect human health and threaten life in today's society. Natural killer cells (NK cells) are one of the main anti-tumor immune cells in the body. They can directly kill tumors and virus-infected cells without prior sensitization, and have received extensive attention in recent years. However, the killing function of NK cells on tumor cells is limited by various factors. How to efficiently activate NK cells in the process of immunotherapy is one of the problems to be solved urgently. [0003] Co-stimulation of multiple activating receptors on the surface of NK cells is a necessary prerequisite for the full activation of NK cells. Interleukin-15 (Interleukin-15, IL-15) is a soluble cytokine secreted by i...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K9/107A61K38/20A61K47/34A61P35/00C08G81/00
CPCA61K38/2086A61K38/2013A61K9/1075A61K47/34C08G81/00A61P35/00A61K2300/00
Inventor 邵东燕黄庆生朱博博白婷孔杰师俊玲
Owner NORTHWESTERN POLYTECHNICAL UNIV
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