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Construction of a stem cell tumor targeting system bound to the surface of drug-loaded nanoparticles

A drug-loaded nanotechnology and tumor-targeting technology, applied in the fields of biomedical technology and nanomedicine, can solve the problems of little involvement and achieve the effect of easy release curve

Active Publication Date: 2019-09-20
CHINA PHARM UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the field of combining drug-loaded nanoparticles on the surface of MSCs membranes to construct stem cell-nanoparticle hybrid carriers has not been involved.

Method used

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  • Construction of a stem cell tumor targeting system bound to the surface of drug-loaded nanoparticles
  • Construction of a stem cell tumor targeting system bound to the surface of drug-loaded nanoparticles
  • Construction of a stem cell tumor targeting system bound to the surface of drug-loaded nanoparticles

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Embodiment 1: Synthesis and characterization of Bio-Chi

[0031] Dissolve 90 mg of chitosan in 1% hydrochloric acid solution and swell overnight, then dilute to 20 mL with 2-morpholine sodium sulfonate buffer solution with pH=5.5. Dissolve 120 mg of biotin, 84 mg of EDC, and 56 mg of NHS in a mixed solvent of 6 mL of DMSO and DMF, and stir at room temperature for 2 h. Add the activated biotin dropwise into the stirring chitosan solution, keep stirring for 24h, and filter to remove the insoluble matter. Place in a dialysis bag and dialyze with deionized water for 2 days, then freeze-dry.

[0032] Infrared spectrum analysis was carried out on the synthesized Bio-Chi, and the results showed that at 1635.6cm -1 The stretching vibration peak of the amide bond appears at 1531.9cm-1, and the stretching vibration peak of the amide bond of the biotin imidazolone ring appears at 1531.9cm-1, indicating that biotin and chitosan have been chemically bonded (attached figure 1 ). ...

Embodiment 2

[0033] Embodiment 2: Preparation and characterization of Cur / Bio-Chi

[0034] Weigh 10mg of Bio-Chi, dissolve in 1mL of 1% acetic acid solution, and swell overnight. With stirring at room temperature, 0.25 mL of 4 mg / mL Cur ethanol solution was added dropwise into the Bio-Chi solution. Stir continuously in a water bath at 50°C for 30min, sonicate with a 50W probe for 30min, dialyze for 6h to remove the organic solvent, pass through a 0.8μm hydrophilic microporous membrane, and dilute to the required concentration with PBS.

[0035] The particle size of Cur / Bio-Chi measured by a laser particle size analyzer was 360.2±2.6nm, and the potential was 9.6±1.9mV.

[0036] Take an appropriate amount of nanoparticle solution, add an equal amount of ethanol and vortex vigorously, measure the absorbance value at λ=431nm, calculate the Cur content in the nanoparticle solution according to the standard curve, and calculate the encapsulation efficiency according to the following formula: en...

Embodiment 3

[0037] Embodiment 3: the release profile of Cur / Bio-Chi

[0038]Take 0.4mL Cur / Bio-Chi, dilute it to 2mL with 10mMPBS7.4, place it in a dialysis bag (MWCO=14,000), tie both ends tightly, and immerse in 5mL of 10mMPBS containing 0.1% Tween 80 (pH=7.4, 6.5, 5.5 )middle. The release was performed at a constant temperature of 37° C. and a rotation speed of 100 rpm. At predetermined time points 2, 4, 8, 12, 24, 36, 48, 60, 72, 96, 120, 144, 168 h, the release medium was collected and replaced with 5 mL of fresh medium. Take 1 mL of the collected release medium, add 1 mL of ethanol, vortex vigorously for 5 min, measure the absorbance value at λ=431 nm with an ultraviolet-visible spectrophotometer, calculate the release amount, and draw the release curve.

[0039] The results showed that in the environment of pH=7.4, Cur / Bio-Chi could keep releasing Cur continuously and slowly for more than 7 days; complete, faster release (attached figure 2 ).

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Abstract

The invention belongs to the technical fields of bio-medicine technique and nanomedicine and particularly relates to building of a stem cell tumor targeting system with surface-bonded drug-loaded nanoparticles. Synthetic material biotinylated chitosan (BiO-Chi) is taken as a nanoparticle carrier of drug curcumin, then biotinylated (B-) mesenchymal stem cells (MSCs) are taken as cell carriers, and the nanoparticle carrier and the cell carriers are in bridge connection through avidin to form a stem cell-nanoparticle mixed carrier with the surface-bonded drug-loaded nanoparticles. The prepared tumor targeting system has the general formula of Cur / Bio-Chi-S-B-MSCs. The stem cell-nanoparticle mixed carrier has not only a controlled release function of polymer nanoparticles but also tumor tropism and low immunogenicity of the stem cell carriers, therefore, a novel way is provided for taking the stem cells as the tumor targeting drug delivery carriers.

Description

technical field [0001] The invention belongs to the fields of biomedical technology and nanomedicine technology, and in particular relates to the construction of a stem cell tumor targeting system bound to the surface of drug-loaded nanoparticles. Background technique [0002] Despite 30 years of development, traditional anticancer drugs still have the disadvantages of non-specific targeting of tumor sites and dose-dependent toxic side effects. The combination of sustained and controlled release technology and targeted delivery technology can help overcome the above problems. The emergence of nanotechnology provides the possibility for the effective delivery of anticancer drugs. The polymer nanoparticle encapsulating the drug can achieve long-term sustained release or environment-responsive release, so that the drug concentration can be maintained within the therapeutic range for a long time, reducing toxic and side effects. Drug-loaded nanoparticles can also passively tar...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K47/61A61K47/54A61K47/69A61K31/12A61P35/00
Inventor 宗莉金亮徐梦露
Owner CHINA PHARM UNIV