Co-loaded liposome based on simultaneous killing of tumor cells and CAFs and preparation method of co-loaded liposome

A tumor cell and liposome technology is applied in the field of co-loaded liposomes based on simultaneous killing of tumor cells and CAFs and their preparation, which can solve the problems of patient death, tumor metastasis and recurrence, and tumor treatment failure.

Pending Publication Date: 2021-09-14
WEIFANG MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, single chemotherapy is difficult to completely eliminate tumor cells, it is easy to

Method used

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  • Co-loaded liposome based on simultaneous killing of tumor cells and CAFs and preparation method of co-loaded liposome
  • Co-loaded liposome based on simultaneous killing of tumor cells and CAFs and preparation method of co-loaded liposome
  • Co-loaded liposome based on simultaneous killing of tumor cells and CAFs and preparation method of co-loaded liposome

Examples

Experimental program
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Embodiment 1

[0032] A co-loaded liposome based on simultaneous killing of tumor cells and CAFs, the co-loaded liposome is co-loaded irinotecan / anti-FAP scFv liposome, prepared from the following components: egg yolk lecithin 95mg , Cholesterol 25mg, DSPE-PEG-R927mg, Irinotecan 15mg, anti-FAP scFv (a kind of single-chain monoclonal antibody, its mass ratio to DSPE-PEG-R9 is 1:540).

[0033] The preparation method of the above-mentioned co-loaded liposomes comprises the following steps: first, dissolve the weighed egg yolk lecithin, cholesterol, DSPE-PEG-R9, and irinotecan in 2mL absolute ethanol, at a speed of 20rpm / min, Inject into 5mL PBS at a temperature of 60°C, and obtain positively charged liposomes after 1 hour; then mix the anti-FAP scFv with the positively charged liposomes and vortex for 15 minutes, pass through 450nm and 200nm filters three times each, Liposomes co-loaded with irinotecan / anti-FAP scFv were obtained.

[0034] After testing, the concentration of irinotecan in the ...

Embodiment 2

[0039] A co-loaded liposome based on simultaneous killing of tumor cells and CAFs, the co-loaded liposome is a co-loaded doxorubicin / anti-FAP scFv liposome, prepared from the following components: soybean lecithin 95mg , Cholesterol 25mg, DSPE-PEG-R927mg, Doxorubicin 5mg, anti-FAP scFv (a kind of single-chain monoclonal antibody, its mass ratio to DSPE-PEG-R9 is 1:270).

[0040]The preparation method of the above co-loaded liposomes comprises the following steps: first, dissolve the weighed soybean lecithin, cholesterol, DSPE-PEG-R9, and doxorubicin in 6 mL of chloroform, and add 2 mL of PBS solution for a short time. Sonicate to form a water-in-oil emulsion, use a rotary evaporator to remove chloroform to form a gel, then add an appropriate amount of PBS to 5mL, and hydrate at 60°C for 1 hour to obtain positively charged liposomes; then anti -FAP scFv was mixed with the positively charged liposome and vortexed for 15 minutes, and passed through 450 nm and 200 nm filter membra...

Embodiment 3

[0043] A co-loaded liposome based on simultaneous killing of tumor cells and CAFs, the co-loaded liposome is a co-loaded Sorafenib / Sirolizumab liposome, prepared from the following components: hydrogenated soybean Phospholipids 95mg, Cholesterol 25mg, DOTAP 4.5mg, Sorafenib 15mg, Cirocizumab (a kind of monoclonal antibody drug, its mass ratio to DOTAP is 1:540).

[0044] The preparation method of the above-mentioned co-loaded liposomes comprises the following steps: first, dissolve the weighed hydrogenated soybean lecithin, cholesterol, DOTAP, and Sorafenib in 4mL chloroform / methanol mixed solution, and use a rotary evaporator to vacuumize and remove Organic solvents were used to obtain a uniform lipid film, and then 5 mL of PBS solution was added to hydrate at 60°C for 1 hour to obtain positively charged liposomes; then the positively charged liposomes were mixed with cilozumab and the above positively charged liposomes were vortexed for 15 min, passed through 450 nm and 200n...

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Abstract

The invention discloses a co-loaded liposome based on simultaneous killing of tumor cells and CAFs and a preparation method thereof and belongs to the technical field of liposome medicaments. The co-loaded liposome is a liposome co-loaded with a micromolecular toxic drug and a macromolecular antibody drug and comprises the following components: phospholipid, cholesterol, the micromolecular toxic drug and the macromolecular antibody drug, and the phospholipid is composed of an anionic lipid and a cationic lipid. The mass ratio of the micromolecular toxic drug to the phospholipid is (1: 5)-(1: 100), the molar ratio of the cationic lipid to the phospholipid is (0.05: 1)-(0.5: 1), the mass ratio of the anionic lipid to the cholesterol is 19: 5, and the mass ratio of the macromolecular antibody drug to the cationic lipid is (1: 45)-(1: 900). According to the co-loaded liposome and the preparation method thereof, specific adsorption and responsive shedding of the macromolecular antibody drug can be achieved, the tumor cells and tumor-related fibroblasts (CAFs) can be killed at the same time, and the treatment effect on colorectal cancer is improved.

Description

technical field [0001] The invention relates to the technical field of liposome medicaments, in particular to a co-loaded liposome based on simultaneously killing tumor cells and CAFs and a preparation method thereof. Background technique [0002] As one of the most common malignant tumors, cancer has high morbidity and mortality. Chemotherapy, as the main means of clinical anti-tumor drug treatment, can directly kill tumor cells, thereby inhibiting the growth and proliferation of tumors. However, single chemotherapy is difficult to completely eliminate tumor cells, and it is easy to cause tumor metastasis and recurrence, resulting in tumor treatment failure and patient death. At present, the biggest obstacle to tumor treatment is tumor metastasis and recurrence. [0003] The tumor microenvironment is the place where tumor cells live. In addition to tumor cells, there are also a large number of stromal cells such as: tumor-associated fibroblasts, tumor-associated macrophag...

Claims

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Application Information

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IPC IPC(8): A61K47/69A61K47/68A61K39/395A61K45/06A61P35/00A61K31/337A61K31/44A61K31/4745A61K31/704A61K33/243
CPCA61K47/6913A61K47/6849A61K45/06A61K39/3955A61K33/243A61K31/4745A61K31/704A61K31/44A61K31/337A61P35/00A61K2300/00
Inventor 张波李兆焕武敬亮李成垒郑增娟
Owner WEIFANG MEDICAL UNIV
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