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Application of sp-agnps nanomaterials and its combination with Salmonella in the preparation of antitumor drugs

A technology of anti-tumor drugs and nanomaterials, applied in the directions of anti-tumor drugs, nano-drugs, anti-bacterial drugs, etc., can solve problems such as opportunistic infection of neutrophils, reduce the risk of damage and infection, and has a significant effect. The effect of improving biosafety

Active Publication Date: 2022-04-01
THE THIRD XIANGYA HOSPITAL OF CENT SOUTH UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, this excessive depletion of neutrophils can easily lead to opportunistic infections, so it is difficult to be accepted by clinical practice

Method used

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  • Application of sp-agnps nanomaterials and its combination with Salmonella in the preparation of antitumor drugs
  • Application of sp-agnps nanomaterials and its combination with Salmonella in the preparation of antitumor drugs
  • Application of sp-agnps nanomaterials and its combination with Salmonella in the preparation of antitumor drugs

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Synthesis of LA-PEG-SA

[0052] Synthesis of LA-PEG-SA by amide reaction between the carboxyl group of sialic acid (SA) and the amino group of LA-PEG-NH2:

[0053] SA (85.9 mg, 0.278 mmol), EDC·HCl (63.9 mg, 0.333 mmol) and NHS (38.4 mg, 0.333 mmol) were dissolved in 5.6 mL DMSO and stirred at room temperature for 2 h to activate the SA carboxyl group. Then SA added LA-PEG-NH2 (200mg, 0.056mmol; manufacturer and grade, especially polymer molecular weight 3400) dissolved in 2mL DMSO, and further stirred for 24h. Afterwards, the reaction solution was dialyzed against water (MWCO=3500) for 48 hours, and then freeze-dried for 24 hours. The product was confirmed by 1HNMR.

Embodiment 2

[0055] Preparation and properties of SA-AgNPs

[0056] AgNPs were prepared by chemical reduction method. Mix 1.2 mL of sodium citrate (100 mM) and 4 mL of NaBH4 (100 mM) with 390.8 mL of water and stir in an ice bath. Then, slowly add 4mLAgNO3 (10mM) and react for 30 minutes. The AgNPs were collected by centrifugation at 20000rpm for 30 minutes (all silver nanoparticles used in subsequent assays were the particles). Then, SA-AgNPs were prepared by modifying LA-PEG-SA on AgNPs via Ag-S bonds. The collected AgNPs were resuspended in water and reacted with LA-PEG-SA for 24 h in the dark. SA-AgNPs were collected by centrifugation at 20000rpm for 30 minutes (this particle was used in the determination of the following cases), and the precipitate was washed and resuspended in water. Average particle size distribution and zeta potential were determined by Malvern ZetaSizerNano series (Nano ZS, Malvern Instruments, UK). Morphology was observed using a transmission electron micros...

Embodiment 3

[0064] Cellular uptake of neutrophils at 1 x 10 5 The density of cells / dish was inoculated in a confocal culture dish, incubated with FITC-labeled SP-AgNPs or PEG-AgNPs for 1 h, and washed 3 times with PBS. The cells were fixed with 4% paraformaldehyde for 20 min, and the nuclei were stained with 1 μg / mL adenosine diphosphate for 10 min. Cell uptake was observed by confocal laser scanning microscopy (CLSM). Seed neutrophils in a 6-well plate at a density of 2×105 / well, incubate with FITC-labeled SP-AgNPs or PEG-AgNPs for 1 h, collect cells, wash with PBS several times, and resuspend in 0.5 mL PBS . Fluorescence intensity was measured by flow cytometry. In addition, cellular uptake into B16F10 cells was also assessed as described above.

[0065]In vitro cytotoxic B16F10 cells were seeded in 96-well plates at a density of 5×103 cells / well and cultured overnight. Then, after adding different concentrations of SP-AgNPs and incubating for 48 h, 100 μL of MTT solution (0.5 mg / m...

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Abstract

The invention belongs to the technical field of functional nanomaterials, and specifically relates to an application of SP-AgNPs nanomaterials, which is characterized in that it is used to prepare antitumor drugs; the SP-AgNPs nanomaterials include nano-silver particles and saliva modified A functional polymer of acid and sulfur; wherein, an Ag-S bond is formed between the described silver nanoparticles and the sulfur of the functional polymer. The present invention also discovers the synergistic effect of the SP-AgNPs nanometer material and Salmonella in anti-tumor. The present invention combines SA-AgNPs and Salmonella, which can significantly synergistically improve the anti-tumor activity, and also has good treatment safety.

Description

technical field [0001] The invention belongs to the field of medical biomaterials, in particular to the field of anti-tumor technology. Background technique [0002] In recent years, microorganism-based tumor microenvironment immunotherapy has received special attention because of its unique way of interacting with host cells. Pathogenic microorganisms such as Escherichia coli, Salmonella, and Plasmodium have become hot spots and innovations in tumor treatment. Some breakthroughs have been made in the experiments. Among them, Salmonella has inherent natural advantages in the treatment of tumors. First, Salmonella that grows facultatively and anaerobically can automatically target tumors according to the particularity of the tumor microenvironment. Second, the advantage of easy genetic engineering of Salmonella can be a good carrier; Third, Salmonella implanted in tumors may change the tumor immune microenvironment in some ways, activate intratumoral immunity, and kill tumor...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/54A61K47/60A61K33/38A61K35/74A61P31/04A61P35/00B82Y5/00C08G83/00
CPCA61K47/542A61K47/545A61K47/60A61K33/38A61K35/74A61P35/00A61P31/04B82Y5/00C08G83/001A61K2300/00Y02A50/30
Inventor 容鹏飞米泽周文虎孙宇刘佳豪
Owner THE THIRD XIANGYA HOSPITAL OF CENT SOUTH UNIV
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