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Lycium barbarum polysaccharide modified nano particle preparation and anti-tumor activity research

An anti-tumor activity, Lycium barbarum polysaccharide technology, applied in the direction of anti-tumor drugs, organic active ingredients, medical preparations of non-active ingredients, etc., can solve the problems of reduced drug efficacy, poor selectivity, fast metabolism, etc. and toxic side effects

Active Publication Date: 2019-06-14
YANCHENG TEACHERS UNIV
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  • Abstract
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Problems solved by technology

[0002] Cancer, as a fatal disease, has been closely watched by researchers. Platinum drugs can combine with chromosomal DNA in the nucleus, which is the main mechanism of anti-tumor drugs. Among various anti-cancer drugs, the use of platinum drugs occupies However, traditional small molecule platinum anticancer drugs have dose-limiting toxicity, such as neurotoxicity, nephrotoxicity, short cycle, fast metabolism, poor selectivity and drug resistance, etc., which limit platinum Clinical application of platinum-based drugs (Mol. Neurobiol. 2017, 10, 364-367); in order to reduce the damage of platinum-based anticancer drugs to normal tissues, nanoparticle drug delivery system can be used for the delivery of platinum-based anticancer drugs (Eur. J . Med. Chem. 2018, 155, 639-650, Adv. Polym. Nanopart. 2015, 7, 17964-17979)
[0003] Nanoparticle drug delivery system can improve the delivery efficiency of anticancer drugs and reduce drug side effects. Its main purpose is to prevent non-targeted tissues or parts from being exposed to therapeutic drugs, or damage targeted tissues due to high doses of specific drugs. (ACS Symp. Ser. 2006, 934, 289-303, Tissue Barriers. 2014, 2: 58-65), but the effect of single drug system is relatively weak, long-term use stimulates other related malignant proliferation mechanisms of tumors, resulting in reduced drug efficacy, Adverse reactions such as tumor recurrence, while the intelligent polysaccharide drug delivery system provides an effective therapeutic method, which can be released at the fixed point of the diseased tissue or cells, and can also be released in specific damage and specific physiological environment (Biomaterial, 2014, 35, 6439-6453)

Method used

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  • Lycium barbarum polysaccharide modified nano particle preparation and anti-tumor activity research

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Experimental program
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Effect test

Embodiment 1

[0026] 500 mg of Lycium barbarum polysaccharide was completely dissolved with 100 mL of pH=2 buffer solution, then 500 mg of 5-aminosalicylic acid (5-ASA) was added and stirred at 25°C for 24 h, then 500 mg of compound 1 was added once Add the solution to the above mixed solution, react at room temperature for 24 hours, place the mixed solution in a dialysis bag (MWCO: 3500 Da) and dialyze with deionized water for 48 hours, and freeze-dry the solution to obtain composite nanoparticles LBP / 5-ASA / Pt.

[0027] Lung cancer cells (A549) and normal hepatocytes (293A) were incubated with 100.0 μL of 1640 medium and DMEM for 24 h, respectively, and 100 μL of 40 μg / mL composite nanoparticles LBP / 5-ASA / Pt After 48 hours of treatment, MTT (20 μL 5 mg / mL) was added, and placed in an incubator to continue culturing for 4 hours. The purple precipitate produced in the separation system was dissolved in 200 μL dimethyl sulfoxide solution, and the absorbance was measured. The IC 50 They are ...

Embodiment 2

[0029] 500 mg of Lycium barbarum polysaccharide was completely dissolved in 100 mL of pH=5 buffer solution, then 500 mg of 5-aminosalicylic acid (5-ASA) was added and stirred at 25°C for 24 h, and 500 mg of compound 1 was dissolved in one time Add the above mixed solution, react at room temperature for 24 hours, place the mixed solution in a dialysis bag (MWCO: 3500 Da) and dialyze with deionized water for 48 hours, and freeze-dry the solution to obtain composite nanoparticles LBP / 5-ASA / Pt .

[0030] Lung cancer cells (A549) and normal liver cells (293A) were incubated with 100.0 μl of 1640 medium and DMEM base for 24 h, respectively, and 100 μL, 40 μg / mL of composite nanoparticles LBP / 5-ASA / Pt, after 48 hours of treatment, MTT (20 μL 5 mg / mL) was added, placed in the incubator for 4 hours, and the purple precipitate produced in the separation system was dissolved in 200 μL dimethyl sulfoxide solution, and the absorbance was measured. The IC 50 They were 40 μg / mL and 195 μg / ...

Embodiment 3

[0032] 500 mg of Lycium barbarum polysaccharide was completely dissolved with 100 mL of pH=7 buffer, then 500 mg of 5-aminosalicylic acid (5-ASA) was added and stirred at 25°C for 24 h, then 500 mg of compound 1 was added once Add the solution to the above mixed solution, react at room temperature for 24 hours, place the mixed solution in a dialysis bag (MWCO: 3500 Da) and dialyze with deionized water for 48 hours, and freeze-dry the solution to obtain composite nanoparticles LBP / 5-ASA / Pt.

[0033] Lung cancer cells (A549) and normal liver cells (293A) were incubated with 100.0 μl of 1640 medium and DMEM base for 24 h, respectively, and 100 μL, 40 μg / mL of composite nanoparticles LBP / 5-ASA / Pt, after 48 hours of treatment, MTT (20 μL 5 mg / mL) was added, placed in the incubator for 4 hours, and the purple precipitate produced in the separation system was dissolved in 200 μL dimethyl sulfoxide solution, and the absorbance was measured. The IC 50 They were 107 μg / mL and 182 μg / ...

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Abstract

The invention provides lycium barbarum polysaccharide modified nanoparticle preparation and anti-tumor activity research, and particularly relates to low-toxicity composite nanoparticles (LBP / 5-ASA / Pt) prepared by takinglycium barbarbarum polysaccharide as a main chain and conducting covalent bonding on 5-aminosalicylic acid and a platinum complex, and the anti-cancer effect of drugs is improved.By determining the semi-lethal number of cells (IC50),it is shown that the composite nanoparticles havevery strong lethalityand inhibitionon lung cancer cells, wherein the semi-lethal number reaches 40 microgram / mL, but the composite nanoparticleshave little toxicity to normal live cells of the human body. Accordingly, the lycium barbarum polysaccharide is utilized as the main body to modify bonded molecules, and a new idea is provided for modification and application of highly-toxic anticancer drugs.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry and relates to the preparation of a class of nanometer particles modified by Lycium barbarum polysaccharide and the research on its antitumor activity. Background technique [0002] Cancer, as a fatal disease, has been closely watched by researchers. Platinum drugs can combine with chromosomal DNA in the nucleus, which is the main mechanism of anti-tumor drugs. Among various anti-cancer drugs, the use of platinum drugs occupies However, traditional small molecule platinum anticancer drugs have dose-limiting toxicity, such as neurotoxicity, nephrotoxicity, short cycle, fast metabolism, poor selectivity and drug resistance, etc., which limit platinum Clinical application of platinum-based drugs (Mol. Neurobiol. 2017, 10, 364-367); in order to reduce the damage of platinum-based anticancer drugs to normal tissues, nanoparticle drug delivery system can be used for the delivery of platinum-based anti...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K47/69A61K31/282A61K31/606A61P35/00
CPCY02A50/30
Inventor 王彦卿王莹孙世新韩倩倩张红梅费正皓
Owner YANCHENG TEACHERS UNIV
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