Fullerene nanoparticles for enhancing antitumor immunotherapy

An anti-tumor immunity and nanoparticle technology, applied in the field of fullerene nanoparticles, can solve problems such as cytotoxicity and achieve high tumor inhibition rate, enhanced therapeutic effect, and significant effect.

Active Publication Date: 2020-08-11
INST OF CHEM CHINESE ACAD OF SCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Conventional small-molecule drugs such as LPS also regulate the function of tumor-associated macrophages, but their use is limited due to cytotoxicity caused by long-term use

Method used

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  • Fullerene nanoparticles for enhancing antitumor immunotherapy
  • Fullerene nanoparticles for enhancing antitumor immunotherapy
  • Fullerene nanoparticles for enhancing antitumor immunotherapy

Examples

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preparation example Construction

[0083] The present disclosure also relates to the preparation method of the fullerene nanoparticle, the amino acid-modified fullerene water-soluble modification obtained by modifying the fullerene or metal fullerene with a hydroxyl group and a water-soluble amino acid.

[0084] In a specific embodiment, the fullerene solid powder is reacted with the water-soluble amino acid under alkaline solution, or the organic solution of fullerene is reacted with the water-soluble amino acid alkaline solution under the phase transfer catalyst.

[0085] In a specific embodiment, the preparation method includes the following steps:

[0086] 1) prepare the alkali solution of water-soluble amino acid;

[0087] 2) Add the alkali solution in step 1) into the container filled with fullerene solids and stir for reaction.

[0088] Preferably, the mass fraction of alkali in the alkali solution is 15-60%; more preferably 28-40%;

[0089] Preferably, the molar ratio of the water-soluble amino acid t...

Embodiment 1

[0105] Embodiment 1: Preparation of water-soluble amino acid metallofullerene

[0106] 1) Add 100mg Gd@C 82 Add the solid powder (purchased from Xiamen Funa New Material Technology Co., Ltd.) into a 100ml single-mouth bottle, add 7.2g of β-alanine and 100mL of 14% sodium hydroxide aqueous solution respectively, heat the oil bath to 80°C, and react 4- 7 hours.

[0107] 2) After the reaction, use a M.W.=3500 dialysis bag to remove small molecules, use a conductivity meter to monitor the conductivity until the dialysis is completed, and concentrate the obtained product to obtain alanine-modified gadolinium metallofullerene hydroxylated modified (GF-Ala ), its average particle diameter in aqueous solution measured by dynamic light scattering (DLS) is 144nm ( figure 1 ), with a uniform particle size distribution.

Embodiment 2

[0108] Example 2: Tumor immunotherapy effect of water-soluble amino acidated metal fullerene

[0109] 1) Induction of water-soluble amino acidated metallofullerenes on the polarization of macrophages

[0110] Cells: RAW264.7 cell line

[0111] Grouping: blank control group, induction group (IL-4), single administration group (GF-Ala) and induction administration group (IL-4+GF-Ala)

[0112] (1) After the RAW264.7 cell line was in a stable culture state in vitro, IL-4 was induced by group. After 24 hours, the supernatant was aspirated, washed with PBS, and GF-Ala (50 μM) or PBS was added according to the group. The culture was continued for 24 hours. In the supernatant, the levels of cytokines such as TNF-α, IL-6, IL-12 (M1-related cytokine) and IL-10 (M2-related cytokine) were detected by enzyme-linked immunosorbent assay kit (ELISA).

[0113] (2) ELISA test results showed ( figure 2 ), the fullerene treatment group can significantly increase the content of M1-related cyto...

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Abstract

The invention relates to an application of fullerene nanoparticles in preparation of a drug for tumor immunotherapy. The fullerene nanoparticles comprise an amino acid modified fullerene water-solublemodifier; the drug can activate immune cells, polarize tumor-associated macrophages and / or improve T lymphocyte infiltration at a tumor site; and the treatment effect of an antitumor immunity drug PD-L1 inhibitor is enhanced.

Description

technical field [0001] The disclosure relates to the field of biomedicine, in particular to a fullerene nanoparticle capable of regulating the phenotype of tumor-associated macrophages, enhancing the therapeutic effect of immune checkpoint inhibitors, and realizing anti-tumor immunotherapy. Background technique [0002] Cancer, also known as malignant tumor, is the abnormal proliferation and metastasis of cells caused by the loss of normal gene regulation of cells in local tissues under the stimulation of various carcinogenic factors. The current effective diagnosis and treatment of cancer has become one of the major problems that need to be solved urgently in contemporary medicine. At present, conventional cancer treatment mainly includes chemotherapy and radiotherapy, but they all face many challenges. For example, chemotherapy introduces chemotherapy drugs into cancer patients through injection and oral administration. Due to the poor selectivity of chemotherapy drugs, in...

Claims

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Application Information

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IPC IPC(8): A61K47/54A61K47/69A61K33/24A61K33/244A61K33/44A61K39/395A61K45/06A61P35/00A61P37/04C01B32/156
CPCA61K33/44A61K33/24A61K33/244A61K47/6949A61K47/542A61K45/06A61K39/3955A61P35/00A61P37/04C01B32/156A61K2300/00
Inventor 王春儒李蕾甄明明
Owner INST OF CHEM CHINESE ACAD OF SCI
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