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Cancer cell membrane-coated drug-loaded lignin nanoparticles as well as preparation method and application thereof

A nanoparticle, cancer cell membrane technology, applied in the fields of chemical materials and biomedicine, can solve problems such as increased safety risk, long time, residue, etc.

Pending Publication Date: 2021-09-10
JINAN UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, at present, toxic and volatile organic solvents are often used in nano-lignin as a carrier for loading drugs, which undoubtedly increases the safety risk of production.
In addition, the currently used nano-lignin-loaded drug method often uses a low-concentration dialysis method, which requires a large amount of water and a long time; or is prepared by step-by-step synthesis of nano-lignin and adsorption-loaded drugs. Not only the production efficiency is reduced, but also the drug loading efficiency is low
Finally, the nano-lignin carriers themselves do not possess the ability to actively target cancer cells

Method used

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  • Cancer cell membrane-coated drug-loaded lignin nanoparticles as well as preparation method and application thereof
  • Cancer cell membrane-coated drug-loaded lignin nanoparticles as well as preparation method and application thereof
  • Cancer cell membrane-coated drug-loaded lignin nanoparticles as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043]Example 1: Preparation of loaded gambogic acid lignin nanoparticles (GA-LNPs)

[0044] In order to fully combine the lignin with the drug, we mixed 100 μL 40 mg / mL lignin γ-valerolactone / water system (GWS) solution (GWS solution contains 80vol% γ-valerolactone (GVL)) with 80 μL 1 mg / mL lignin The GWS solution of gambogic acid (GA) in mL (the GWS solution contains 80 vol% GVL) was mixed at room temperature (30° C.) and kept overnight in the dark to obtain a mixed solution. Afterwards, the mixture was added dropwise to 5 mL of deionized water, stirred gently at 30 °C for 2 h, after the reaction was completed, the gambogic acid / lignin nanoparticles (GA-LNPs) were collected by centrifugation (10000 g, 10 min), and then used Wash with deionized water twice. The input mass ratio of the lignin of present example 1 and gambogic acid (GA) is 50:1.

[0045] The obtained GA-LNPs have a particle size of about 130 nm and a zeta potential of about -28 mV. The encapsulation efficien...

Embodiment 2

[0050] Example 2: Extraction of Cancer Cell Membrane (CCM) Fragments

[0051] Mouse breast cancer cells (4T1 cells, purchased from ATCC) were cultured in a petri dish with a diameter of 15 cm, and then the cells were collected with a cell scraper, centrifuged at 700 g for 10 min to obtain a cell pellet, which was the membrane protein of 4T1 cancer cells; It was resuspended in hypotonic cell lysate (containing cell membrane extraction reagent and phenylmethanesulfonyl fluoride PMSF, purchased from Shanghai Biyuntian Biotechnology Co., Ltd., and placed at 4°C for 10-15 minutes to obtain 4T1 cancer cells The lysate; then, break the cells by repeated freezing and thawing, centrifuge at 700g for 10min at 4°C, carefully collect the supernatant, and then centrifuge at 14000g for 30min to obtain cell membrane (CCM) fragments; disperse the cell membrane fragments in In water, prepare a 1.5 mg / mL cell membrane (CCM) dispersion for later use.

Embodiment 3

[0052] Example 3: Preparation of cancer cell membrane-wrapped drug-loaded lignin nanoparticles (GA-LNPs@CCM)

[0053] First, the GA-LNPs (1 mg / mL, 1 mL) in Example 1 and the CCM dispersion (1.5 mg / mL, 1 mL) in Example 2 were mixed evenly under stirring. Subsequently, the mixture was sequentially extruded through polycarbonate microporous filters with different pore sizes (1 μm, 0.8 μm, 0.45 μm) using an Avanti micro-extruder to obtain cancer cell membrane-wrapped drug-loaded lignin nanoparticles (GA- LNPs@CCM). Then, the standard protein (bovine serum albumin was purchased from Aladdin Company), 4T1 cancer cell lysate, 4T1 cancer cell membrane protein and GA-LNPs@CCM were verified by SDS-PAGE protein gel electrophoresis, and the results were as follows figure 2 shown.

[0054] figure 2 The results of SDS-PAGE protein gel electrophoresis showed that the membrane protein component of GA-LNPs@CCM was a cancer cell membrane protein, and that the cancer cell membrane successfu...

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Abstract

The invention discloses cancer cell membrane-coated drug-loaded lignin nanoparticles as well as a preparation method and application thereof, and belongs to the field of chemical materials and biomedicine. The preparation method of the cancer cell membrane-coated drug-loaded lignin nanoparticles comprises the following steps: (1) uniformly mixing a gamma-valerolactone / water system solution containing lignin and a gamma-valerolactone / water system solution containing a drug to obtain a mixed solution; adding the mixed solution to water for dilution and stirring, and after complete reaction, performing centrifuging and collecting to obtain gambogic acid / lignin nanoparticles; and (2) uniformly mixing the gambogic acid / lignin nanoparticles with a cell membrane dispersion liquid, and performing extruding to obtain the cancer cell membrane-coated drug-loaded lignin nanoparticles. Cancer cell membrane wrapping (GA-LNPs (at) CCM) of the lignin drug-loaded nanoparticles is realized, so that the lignin drug-loaded nanoparticles have the advantages of good biocompatibility, specific tumor targeting, small toxic and side effects on organisms and the like.

Description

technical field [0001] The invention belongs to the fields of chemical materials and biomedicine, and in particular relates to a cancer cell membrane-wrapped drug-loaded lignin nanoparticle and a preparation method and application thereof. Background technique [0002] Cancer is one of the main causes of abnormal death of human beings. Chemotherapy remains the mainstay of cancer treatment. However, the drugs used in chemotherapy have poor drug performance and strong side effects. They can treat cancer while indiscriminately damaging normal tissue cells, destroying the human immune system and increasing the risk of cancer recurrence. The use of nano-carriers can improve drug performance and reduce toxic and side effects. For example, polymer self-assembled nanomaterials can effectively improve the loading efficiency of commonly used hydrophobic drugs, and their proper modification can improve the targeting of drugs and reduce toxic and side effects. However, if nanocarrier...

Claims

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Application Information

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IPC IPC(8): A61K9/51A61K47/30A61K47/46A61K31/352A61P35/00
CPCA61K9/5176A61K31/352A61P35/00
Inventor 陈理恒薛巍朱静宜施云峰霍聪敏罗司曼
Owner JINAN UNIVERSITY
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