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Zwitter ion modified dendritic macromolecular composite material, as well as preparation and application thereof

A dendrimer, zwitterion technology, which can be used in preparations for in vivo experiments, preparation of X-ray contrast agents, general/multifunctional contrast agents, etc. Temperature dependence, decomposition, etc.

Active Publication Date: 2018-12-21
DONGHUA UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The technical problem to be solved by the present invention is to provide a dendrimer composite material modified by zwitterions and its preparation and application, which overcomes the temperature dependence of the antifouling performance of PEG in the prior art and is easily decomposed by oxidation , and when combined with a therapeutic protein, it will also reduce the affinity of the protein and the overall biological activity of the defect

Method used

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  • Zwitter ion modified dendritic macromolecular composite material, as well as preparation and application thereof
  • Zwitter ion modified dendritic macromolecular composite material, as well as preparation and application thereof
  • Zwitter ion modified dendritic macromolecular composite material, as well as preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0085] Weigh 10 mg of the fifth-generation PAMAM dendrimer (G5) and 20 mg of CBAA, dissolve them in 5 mL of methanol and 5 mL of NaCl solution (0.138 M), and after each is completely dissolved, stir at room temperature for 3 days to obtain the product G5 .NH 2 -CBAA 20 . Dialyze with a dialysis bag with a molecular weight cut-off of 10,000 for three days (dialyze in PBS buffer for one day, change water 3 times; dialyze in distilled water for 2 days, change water 6 times), freeze-dry to obtain G5.NH 2 -CBAA 20 ;

[0086] Weigh 10 mg of the fifth-generation PAMAM dendrimer (G5) and 26.5 mg of MPC, and dissolve them in 5 mL of ultrapure water respectively. After each is completely dissolved, stir warmly for 3 days to obtain the product G5.NH 2 -MPC 20 . Dialyze with a dialysis bag with a molecular weight cut-off of 10,000 for three days (dialyze in PBS buffer for one day, change water 3 times; dialyze in distilled water for 2 days, change water 6 times), freeze-dry to obtai...

Embodiment 2

[0091] Take respectively {(Au 0 ) 100 -G5.NHAc-CBAA 20}, {(Au 0 ) 100 -G5.NHAc-MPC 20} and {(Au 0 ) 100 -G5.NHAc-PS 20} each 5mg, respectively dissolved in 500μL D 2 O, carry out hydrogen spectrum analysis (as attached figure 2 shown). figure 2 (a) is {(Au 0 ) 100 -G5.NHAc-CBAA 20}, 1.89ppm is the characteristic peak of CBAA, 1.8ppm is the peak of acetyl group, and 2.2-3.3ppm is the peak of G5. After integration, it can be obtained that 19.3 CBAAs are modified on each G5. figure 2 (b) is {(Au 0 ) 100 -G5.NHAc-MPC 20}, 1.9ppm is the characteristic peak of MPC, 1.8ppm is the peak of acetyl group, and 2.2-3.3ppm is the peak of G5. After integration, it can be obtained that 20.2 MPCs are modified on each G5. figure 2 (c) is {(Au 0 ) 100 -G5.NHAc-PS 20}, 1.93ppm is the characteristic peak of PS, 1.8ppm is the peak of acetyl group, and 2.2-3.3ppm is the peak of G5. After integration, it can be obtained that 19.8 1,3-PS are modified on each G5.

Embodiment 3

[0093] Take respectively {(Au 0 ) 100 -G5.NHAc-CBAA 20}, {(Au 0 ) 100 -G5.NHAc-MPC 20} and {(Au 0 ) 100 -G5.NHAc-PS 20} each 0.5 mg, respectively dissolved in 1 mL of ultrapure water for potential particle size testing (as shown in Table 1). {(Au 0 ) 100 -G5.NHAc-CBAA 20}, {(Au 0 ) 100 -G5.NHAc-MPC 20} and {(Au 0 ) 100 -G5.NHAc-PS 20} The hydrated particle diameters are 143.7nm, 132.4nm and 176.3nm, respectively. The modification of zwitterions will form a thick hydration layer on the surface of the particles. Different types of zwitterions have different abilities to form a hydration layer. According to the data, it can be seen that the hydration layer is thicker after PS modification. {(Au 0 ) 100 -G5.NHAc-CBAA 20}, {(Au 0 ) 100 -G5.NHAc-MPC 20} and {(Au 0 ) 100 -G5.NHAc-PS 20} Zeta potentials are: 5.1mV, 4.8mV and 5.3mV, respectively. The potentials of several materials are close to 0, which guarantees the low cytotoxicity of the materials.

[00...

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Abstract

The invention relates to a zwitter ion modified dendritic macromolecular composite material, as well as preparation and application thereof. The composite material is dendritic macromolecular, and ismodified with zwitter ions and a targeting reagent RGD and chelated with gadolinium ions on the surface, and a gold nanoparticle is wrapped therein. The composite material is prepared by the followingsteps: preparing a G5-DOTA-(PEG-RGD) aqueous solution, adding an HAuCl4 solution and NaBH4 for reduction, adding dropwise a gadolinium nitrate solution, performing stirring for 12 h, adding dropwise1,3-PS, performing reaction for 24 h, and performing dialysis and lyophilization. The method is simple and has industrial and commercial potential, and the prepared nanoparticle is long in blood half-life in a mouse, and has a tumor CT / MRI dual-mode tomographic function at the animal level.

Description

technical field [0001] The invention belongs to the field of dendritic macromolecular composite material and its preparation and application, in particular to a zwitterion-modified dendritic macromolecular composite material and its preparation and application. Background technique [0002] CT imaging can perform 3D reconstruction of images, and has the advantages of high spatial resolution, short image acquisition time, and low price, but its soft tissue resolution is poor and has shortcomings such as radiation, while MRI has no radioactive radiation and has high soft tissue resolution, but It is expensive and takes a long time to scan. However, when CT and MRI are used as medical imaging detection methods in a complementary form, two imaging contrast agents, CT and MRI, are usually required. Although a variety of CT or MRI imaging contrast agents can achieve better contrast effects, if two contrast agents are used, on the one hand, it will cause inconvenience to clinical ...

Claims

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Application Information

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IPC IPC(8): A61K49/04A61K49/10A61K49/12
CPCA61K49/0002A61K49/04A61K49/108A61K49/124
Inventor 史向阳刘晋源熊智娟彭琛张九龙
Owner DONGHUA UNIV
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