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Polymer vesicle with antigen double-capture function as well as preparation method and application of polymer vesicle

A technology of polymers and vesicles, applied in the field of anti-tumor, can solve the problems of light instability and poor photothermal effect, and achieve the effect of enhanced recurrence and metastasis, strong accuracy, and small toxic and side effects

Pending Publication Date: 2022-07-08
INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, free ICG has the characteristics of easy degradation, light instability and poor photothermal effect.

Method used

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  • Polymer vesicle with antigen double-capture function as well as preparation method and application of polymer vesicle
  • Polymer vesicle with antigen double-capture function as well as preparation method and application of polymer vesicle
  • Polymer vesicle with antigen double-capture function as well as preparation method and application of polymer vesicle

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] The present embodiment is a preparation method of a polymer vesicle (denoted as mal-dot-PS) with antigen dual capture function, and the preparation method includes the following steps:

[0070] (a) 20 mg of PCL8000-PEG8000-PCL8000 and 1 mg of the hydrophobic TLR7 / 8 agonist IMQ were dissolved in 5 mL of a mixed solvent of dichloromethane and methanol, then the organic solvent was removed by rotary evaporation, and a uniform film was formed in the flask ;

[0071] (b) The film was vacuum-dried for 12 h, and 5 mL of deionized water was added for hydration. The hydration temperature was 65 °C, and the hydration time was 5 h. After the hydration was completed, it was cooled to room temperature, and NaHCO was added. 3 Mix well, the final concentration is 300mM, ultrasonicate with a sonicator for 30min under ice bath conditions, and then dialyze for 8h with a dialysis bag with a molecular weight cut-off of 8000-14000Da, and collect the solution after dialysis;

[0072] (c) Di...

Embodiment 2

[0075] The present embodiment is a preparation method of photothermal sensitive polymer vesicles (referred to as NIPS), and the preparation method comprises the following steps:

[0076] (1) Dissolve PCL8000-PEG8000-PCL8000 20 mg, hydrophobic ICG 0.36 mg, and hydrophobic indoleamine 2,3-dioxygenase-1 pathway interfering agent NLG919 1 mg in 5 mL of dichloromethane to obtain a solvent, and then rotary evaporation organic solvent dichloromethane, and form a layer of uniform film on the flask;

[0077] (2) After vacuum drying the film for 12h, add 5mL of deionized water for hydration. The hydration temperature is 65°C and the hydration time is 5h. After the hydration is completed, it is cooled to room temperature, and NaHCO is added. 3 Mix well, the final concentration is 300mM, ultrasonicate with a sonicator for 30min under ice bath conditions, then centrifuge twice with a high-speed centrifuge at 2000rpm for 30min each time, collect the precipitate after centrifugation and resu...

experiment example 1

[0087] 1. The particle size distribution and potential of the polymer vesicles mal-dot-PS and NIPS were measured. The measurement results showed that the average particle size of the NIPS polymer vesicles was 207.57±0.80nm, the particle size distribution was 0.288, and the potential value was 207.57±0.80nm. -22.07±0.15mV; the average particle size of the mal-dot-PS polymersomes was 166.67±0.22nm, the particle size distribution was 0.202, and the potential value was 8.55±0.005mV.

[0088] 2. The polymer vesicle solution of Example 2 was freeze-dried, and 1 mg of nanoparticles was dissolved in 1 mL of dimethyl sulfoxide, uniformly mixed, and then diluted; and the absorbance was measured with an ultraviolet spectrophotometer, and the measurement wavelength was 280 nm; The content of NLG919 in the sample was calculated by the standard curve method, and the encapsulation efficiency and drug loading of NLG919 were calculated;

[0089] The absorbance of the high-speed centrifuged sup...

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Abstract

The invention discloses a polymer vesicle with an antigen double-capture function as well as a preparation method and application of the polymer vesicle. The method comprises the following steps: dissolving PCL-PEG-PCL and hydrophobic IMQ in an organic solvent, and removing the organic solvent to form a thin film; drying the film, hydrating, adding sodium bicarbonate, uniformly mixing, carrying out ultrasonic treatment and dialysis, and collecting a dialyzed solution; the preparation method comprises the following steps: dissolving DOTAP, DSPE-PEG2K-Mal, DSPE-PEG5K-Mannose and MPLA in an organic solvent to form a thin film, and adding a dialyzed solution into the thin film for hydration; uniformly mixing the hydrated mixture, and performing ultrasonic treatment under an ice bath condition; the polymer vesicle prepared by the invention has an antigen capture effect, releases IMQ at the same time, can promote the activation and maturation of BMDCs and lysosome escape, effectively activates the cellular immunocompetence of CD4 + T cells and CD8 + T cells, generates a strong T cell killing effect, promotes the generation of cell factors IFN-gamma and TNF-alpha, and generates a long-term immune memory effect.

Description

technical field [0001] The invention relates to the technical field of anti-tumor, in particular to a polymer vesicle with antigen dual capture function and a preparation method and application thereof. Background technique [0002] Malignant tumors are still a difficult problem to be solved urgently, posing a great threat to human life and health. Common treatment methods include surgery, chemotherapy and radiotherapy. These three treatment methods can improve the quality of life of patients with advanced cancer and prolong the life of patients. Time has a greater effect, however, it brings serious challenges to the cure of cancer, and at the same time, it brings unbearable side effects to patients. Therefore, people have been looking for emerging treatment methods, and tumor immunotherapy is a breakthrough in the treatment of malignant tumors. In the February 4, 2016 annual report on research progress in malignant tumors, immunotherapy was rated as the greatest progress i...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69
CPCA61K47/6915A61K47/544A61K41/0052A61K39/39A61K31/4188A61K47/02A61P35/00A61P35/04A61P37/04A61K2039/55511A61K2300/00Y02A50/30
Inventor 朱敦皖张琳华左月月黄晨露王涵泳
Owner INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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