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Phospholipid hybrid polymer micelle capable of being co-loaded with immunologic adjuvant and indocyanine green and having targeting effect, and preparation method and application of phospholipid hybrid polymer micelle

An immunoadjuvant, indoqing green technology, applied in the field of combination therapy for the treatment of malignant tumors

Active Publication Date: 2021-09-10
INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, after PDT treatment, regulatory T cells (Regulatory T cells, Tregs) will increase and the expression of PD-L1 will be up-regulated, thereby inhibiting the killing effect of immune cells such as T lymphocytes on tumors

Method used

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  • Phospholipid hybrid polymer micelle capable of being co-loaded with immunologic adjuvant and indocyanine green and having targeting effect, and preparation method and application of phospholipid hybrid polymer micelle
  • Phospholipid hybrid polymer micelle capable of being co-loaded with immunologic adjuvant and indocyanine green and having targeting effect, and preparation method and application of phospholipid hybrid polymer micelle
  • Phospholipid hybrid polymer micelle capable of being co-loaded with immunologic adjuvant and indocyanine green and having targeting effect, and preparation method and application of phospholipid hybrid polymer micelle

Examples

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preparation example Construction

[0055] The present invention provides a method for preparing a phospholipid hybrid polymer micelle of a co-loaded immune adjuvant with targeting effect and indocyanine green, comprising the following steps:

[0056] (a) PCL-ss-PEG-ss-PCL, hydrophobic ICG, DSPE-PEG-COOH, MnO 2 and immune adjuvant are dissolved in an organic solvent and sonicated, and then, the organic solvent is removed and a uniform film is formed;

[0057] (b) performing hydration, ultrasonic treatment and dialysis in sequence after drying the film to obtain a nanoparticle micellar solution;

[0058] (c) Activate the carboxyl groups on the surface of the nanoparticle micelles in the nanoparticle micellar solution, and then add NH to the nanoparticle micellar solution 2 -RGD is incubated and dialyzed to obtain the phospholipid hybrid polymer micelle of the co-loaded immune adjuvant with targeting effect and indocyanine green.

Embodiment 1

[0061] This example is a preparation method of a phospholipid hybrid polymer micelle co-loaded with an immune adjuvant and indocyanine green with a targeting effect. The preparation method includes the following steps:

[0062] (a) PCL-ss-PEG-ss-PCL 20mg, hydrophobic ICG 1mg, MnO 2 0.2mg, DSPE-PEG-COOH1mg and immune adjuvant were dissolved in 5mL of organic solvent and sonicated, then, the organic solvent was rotovaped and a uniform film was formed on the flask, wherein the organic solvent was dichloromethane; PCL-ss -The molecular weight of PEG in PEG-ss-PCL is 2000; the immune adjuvant is indoleamine 2,3-dioxygenase-1 pathway disruptor and TLR4 agonist, PCL-ss-PEG-ss-PCL and indole The mass ratio of amine 2,3-dioxygenase-1 pathway disruptor is 20:1; the mass ratio of PCL-ss-PEG-ss-PCL to TLR4 agonist is 1000:1; indoleamine 2,3- Dioxygenase-1 (IDO1) pathway disruptor is NLG919; TLR4 agonist is MPLA;

[0063] (b) Hydrate the film after vacuum drying for 10 h, place the hydr...

Embodiment 2

[0066] This example is a preparation method of a phospholipid hybrid polymer micelle with a targeted co-loaded immune adjuvant and indocyanine green. The preparation method is basically the same as that of Example 1, the difference is only in step (a) MnO was not added in 2 .

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Abstract

The invention discloses a phospholipid hybrid polymer micelle capable of being co-loaded with immunologic adjuvant and indocyanine green and having a targeting effect, and a preparation method and application of the phospholipid hybrid polymer micelle. The method comprises the following steps of: dissolving PCL-s-PEG-s-PCL, hydrophobic ICG, DSPE-PEG-COOH, MnO2, NLG919 and a TLR4 agonist in an organic solvent, performing ultrasonic treatment, removing an organic solvent, and forming a layer of uniform thin film; drying the thin film, and carrying out hydration, ultrasonic treatment and dialysis in sequence to obtain a nanoparticle micelle solution; and activating carboxyl groups on the surfaces of the nanoparticle micelles in the nanoparticle micelle solution, adding NH2-RGD into the nanoparticle micelle solution for incubation, and dialyzing to obtain the phospholipid hybrid polymer micelle capable of being co-loaded with the immunologic adjuvants (NLG919 and MPLA) and the indocyanine green and having the targeting effect. According to the method, hydrophobic drugs (ICG and NLG919) are effectively wrapped in an inner cavity, an immune agonist is embedded into a phospholipid layer, and aminated polypeptide arginine-glycine-aspartic acid is modified on the surface of a carrier, and therefore, the nano-drug carrier effectively aiming at phototherapy and immunotherapy of malignant tumors is formed.

Description

technical field [0001] The invention relates to the technical field of combination therapy for treating malignant tumors, in particular to a phospholipid hybrid polymer micelle with a targeting effect co-loaded with an immune adjuvant and indocyanine green, and a preparation method and application thereof. Background technique [0002] Cancer is a very challenging health problem facing human beings, and it has become one of the main causes of death in various countries. Chemotherapy is a method commonly used in the treatment of cancer, which has a significant clinical therapeutic effect, but frequent use of chemotherapy drugs will not only cause toxic side effects on normal cells, but also induce multi-drug resistance (MDR) in the body. , MDR), leading to chemotherapy can not achieve the desired effect. In order to overcome the barriers of traditional treatment, the development of effective new methods of cancer treatment is urgent. Chemotherapy, radiotherapy (Radiation th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/107A61K47/24A61K47/34A61K47/62A61K47/69A61K39/39A61K41/00A61K33/32A61P35/00A61P35/04
CPCA61K9/1075A61K47/24A61K47/34A61K47/62A61K47/6909A61K39/39A61K41/0057A61K41/0052A61K33/32A61P35/00A61P35/04A61K2039/55572A61K2039/55511A61K2300/00
Inventor 朱敦皖张琳华张力黄晨露王楠楠
Owner INST OF BIOMEDICAL ENG CHINESE ACAD OF MEDICAL SCI
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