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Polymer nano adjuvant as well as preparation method and application thereof

A polymer and nanotechnology, applied in the fields of biochemical equipment and methods, drug combination, drug delivery, etc., can solve the problems of hypoxia, cancer treatment drug resistance and radiotherapy failure, and achieve inhibition of tumor metastasis, inhibition of primary tumor formation, good water solubility and biocompatibility

Active Publication Date: 2018-08-10
JE & NA BIOTECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, solid tumors often have a hypoxic tumor microenvironment, which leads to drug resistance of cancer therapy and failure of radiotherapy, which is a key unfavorable factor of radiotherapy

Method used

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  • Polymer nano adjuvant as well as preparation method and application thereof
  • Polymer nano adjuvant as well as preparation method and application thereof
  • Polymer nano adjuvant as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Example 1: Preparation of poly(lactic acid-glycolic acid)-imidazoquinoline@catalase (PLGA-R837@Cat) nano adjuvant:

[0046] Encapsulation of catalase (CAT) and immunostimulant imidazoquinoline (R837) into block polymer poly(lactic acid-glycolic acid) (PLGA) by water / oil / water (W / O / W) , forming nanoparticles. Specifically include the following steps:

[0047] Dissolve poly(lactic acid-glycolic acid) (PLGA) in volatile organic solvents such as dichloromethane, and dissolve catalase (CAT) in surfactants such as 1% polyvinyl acetate (PVA). or mixed and ultrasonically obtained the first emulsified solution under ice-bath conditions; then the imidazoquinoline (R837) solution dissolved in dimethyl sulfoxide (DMSO) was added dropwise to the first emulsified solution; and further under ultrasonic conditions Adding 1% polyvinyl acetate (PVA) solution to finally obtain the water / oil / water poly(lactic acid-glycolic acid) nano adjuvant (PLGA-R837@Cat). Then, it is characterized (tr...

Embodiment 2

[0049] Example 2: Preparation of poly(lactic acid-glycolic acid)-monophosphoryl lipid A@catalase (PLGA-A(MPLA)@Cat) nano adjuvant:

[0050] The catalase (CAT) and the immunostimulant monophosphoryl lipid A (A (MPLA)) are wrapped into the block polymer poly(lactic acid-glycolic acid) (PLGA) by the W / O / W method, form nanoparticles. Specifically include the following steps:

[0051] Dissolve poly(lactic acid-glycolic acid) (PLGA) in volatile organic solvents such as dichloromethane, and dissolve catalase (CAT) in surfactants such as 1% polyvinyl acetate (PVA). or were mixed and ultrasonically obtained in an ice bath to obtain the first emulsified solution; then a monophosphoryl lipid A (A(MPLA)) solution dissolved in dimethyl sulfoxide (DMSO) was added dropwise to the first emulsified solution; And further added into a 5% polyvinyl acetate (PVA) solution under ultrasonic conditions to finally obtain a water / oil / water poly(lactic acid-glycolic acid) nano adjuvant (PLGA-R848@Cat)...

Embodiment 3

[0052] Example 3: Determination of Poly(lactic acid-glycolic acid)-immunostimulant @ catalase oxygen production capacity

[0053] Poly(lactic-glycolic acid)-immunostimulant @ catalase (PCR) and poly(lactic-glycolic acid)-immunostimulant (PC) were dissolved in 100 micromolar hydrogen peroxide solution using an oxygen electrode Oxygen produced is detected.

[0054] attached image 3 It is the ability of PCR to generate oxygen in hydrogen peroxide solution. It can be seen that a large amount of oxygen can be generated in the hydrogen peroxide solution added to PCR. This shows that catalase is still active. In contrast, PC without catalase cannot catalyze the decomposition of hydrogen peroxide, and the hydrogen peroxide solution itself is relatively stable and difficult to decompose.

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Abstract

The invention discloses a nano adjuvant of a poly(lactic acid-glycollic acid) covered immunologic stimulant and catalase. The nano adjuvant has a remarkable effect in radiotherapy and immunotherapy. The catalase can be used for effectively improving a tumor hypoxic microenvironment so that the radiotherapy effect is improved; meanwhile, the immunologic stimulant can be used for guiding the immunotherapy on a living body; the activity of regulatory T cells is inhibited, with the help of an immune checkpoint blocking agent; the immunologic stimulant has the effect of inhibiting tumor growth andmetastasis. The invention also discloses a preparation method and application of the nano adjuvant.

Description

technical field [0001] The invention relates to a polymer nano adjuvant, a preparation method thereof, and its use as an adjuvant in combination with an immune checkpoint blocker in tumor radiotherapy. Background technique [0002] Cancer is one of the major malignant diseases that threaten human health. Although a large amount of human, material and financial resources have been invested in the prevention and treatment of cancer for decades since the 1950s, the progress made by human beings in this regard is very limited. [0003] Radiation therapy, as one of the mainstream clinical cancer treatment strategies, mainly refers to the use of X-rays, gamma rays and other ionizing radiation to generate reactive oxygen species free radicals to induce DNA damage, thereby killing cancer cells. Therefore, the degree of damage to cancer cells by radiotherapy depends greatly on the oxygen concentration. Oxygen free radicals can stabilize DNA damage, prevent DNA self-repair after ioni...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/44A61K31/4709A61K31/7024A61K39/395A61K39/39A61K9/14A61K47/34A61P35/00A61P35/04
CPCA61K9/0019A61K9/146A61K31/4709A61K31/7024A61K38/44A61K39/39A61K39/39558A61P35/00A61P35/04C12Y111/01006A61K2300/00
Inventor 刘庄陈倩赵琪
Owner JE & NA BIOTECH CO LTD
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