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Targeted ferrite-loaded multifunctional nanoparticles as well as preparation method and application thereof

A multi-functional, nano-particle technology, applied in general/multi-functional contrast agents, preparations for in vivo tests, wave energy or particle radiation treatment materials, etc., can solve the problem that the safety and sensitivity of imaging agents cannot meet the requirements of atherosclerosis Vulnerable plaque detection needs and other issues

Active Publication Date: 2021-09-17
THE SECOND AFFILIATED HOSPITAL OF CHONGQING MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The present invention intends to provide a targeted ferrite-loaded multifunctional nanoparticle to solve the technical problem that the safety and sensitivity of existing imaging agents cannot meet the detection requirements of atherosclerotic vulnerable plaques

Method used

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  • Targeted ferrite-loaded multifunctional nanoparticles as well as preparation method and application thereof
  • Targeted ferrite-loaded multifunctional nanoparticles as well as preparation method and application thereof
  • Targeted ferrite-loaded multifunctional nanoparticles as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0063] Multifunctional nanoparticles prepared Ferrite carrier targeting: Example 1

[0064] (1) PLGA-PEG 5000 -ramucirumab synthesis

[0065] PLGA-PEG 5000 Chongqing Pu synthesis requesting -ramucirumab Novi for Biological Technology Co., PLGA (polylactic acid - glycolic acid) by PEG 5000 (Polyethylene glycol 5000) covalently linked to the ramucirumab (Lo Remo mAb), PLGA-PEG 5000 -ramucirumab synthetic scheme substantially as follows:

[0066] (1.1) Preparation of PLGA-NHS

[0067] Take PLGA powder was completely dissolved in DCM (dichloromethane). Adding an appropriate amount of NHS (N- hydroxy succinimide) and the appropriate catalyst, stirred at room temperature (20-25 ℃) conditions overnight. Purified by reverse phase chromatography, a low-pressure solution drained, PLGA-NHS to give a sample.

[0068] (1.2) PLGA-PEG 5000 Preparation -COOH

[0069] The PLGA-NHS sample solution with DCM to the original volume, was added an appropriate amount of NH 2-PEG-COOH, into the amount of ...

experiment example 1

[0080] Experimental Example 1: PFP-HMME @ PLGA / MnFe 2 O 4 -Ram characterization of nanoparticles

[0081] The particle diameter of nanoparticles using a dynamic light scattering method of detecting prepared in Example 1 and zeta potential results of the experiment figure 1 , The particle diameter of 347.4 ± 5.93nm, zeta potential was -11.9 ± 0.50nm; nanoparticles prepared in Example 1 as the embodiment of FIG TEM figure 2 Indicated.

[0082] Using low-intensity focused ultrasound (LIFU, 1.5W cm 2 , 1MHz)) irradiation 1,3-diphenyl isobenzofuran DPBF (1,3-diphenyl isobenzofuran, 50μM) and NPs (i.e. nanoparticles, 125μg / mL) mixed solution 150s, for DPBF consumption of each group was quantified. Includes two NPs: PFP-HMME @ PLGA / MnFe 2 O 4 -RAM (for preparation see Example 1) and PFP @ PLGA / MnFe 2 O 4 -RAM (for preparation see Comparative Example 1). Experimental results image 3 As shown in (mean ± SD, n = 4, *** represents compared with the control, p 2 O 4 -Ram + LIFU group ...

experiment example 2

[0091] Experimental Example 2: targeting experiments

[0092] Experiments to detect targeted nanoparticles rabbit aortic endothelial cells (RAEC), the results of the experiment Figure 8 with Figure 9 Indicated. Figure 8 (Subjects of Example 1 and Comparative Example 3 nanoparticles) show nanoparticles DiI- labeled (red fluorescence) and FITC- labeled PLGA-PEG 5000 -ramucirumab (green fluorescence) confocal images. exist Figure 8 Composite image, nanoparticles and Lo Remo mAb overlapping local display yellow. Figure 9 In show, after DiI-labeled targeting nanoparticles and RAEC were incubated for 2 hours, uptake confocal display cells in each group of nanoparticles. It found, PFP-HMME @ PLGA / MnFe 2 O 4 -Ram nanoparticles can be targeted to be swallowed large RAEC, while PFP-HMME @ PLGA / MnFe 2 O 4 The proportion of non-targeted nanoparticles were swallowed RAEC few, in addition, previously incubated with ramucirumab and RAEC, PFP-HMME @ PLGA / MnFe 2 O 4 -Ram targeted nanoparticl...

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Abstract

The invention relates to the technical field of nano atherosclerotic plaque treatment drugs and imaging agents, in particular to targeted ferrite-loaded multifunctional nanoparticles as well as a preparation method and application thereof. Each targeted ferrite-loaded multifunctional nanoparticle comprises a shell formed by a polylactic acid-glycolic acid copolymer, and spinel ferrite and hematoporphyrin monomethyl ether are wrapped in the shell. According to the scheme, the technical problem that the safety and sensitivity of an existing imaging agent cannot meet the detection requirements of the atherosclerotic vulnerable plaques is solved. The nanoparticle is an MRI (Magnetic Resonance Imaging), opto-acoustic and ultrasonic imaging agent with relatively ideal safety and sensitivity, and can be used for detecting and identifying atherosclerosis vulnerable plaques; and the nanoparticles can also be used for effectively intervening artery plaque neovascularization through a sonodynamic therapy, and can be used in medical practice of early recognition and treatment of atherosclerotic plaque neovascularization.

Description

Technical field [0001] The present invention relates to nano atherosclerotic plaque imaging agents and therapeutic drug technology, and in particular relates to a ferrite carrier targeting multifunctional nanoparticles and a preparation method and application. Background technique [0002] Atherosclerosis (Atherosclerosis, AS) vulnerable plaque rupture leading to a stroke (cerebral infarction and cerebral hemorrhage), acute myocardial infarction and peripheral arterial occlusive disease and other diseases are caused by human disability, major cause of death. Neovascularization of atherosclerosis and vulnerable plaque sclerosis abnormal proliferation are closely related. Therefore, early identification and effective intervention atherosclerotic plaque for the prevention of neovascularization vulnerable plaque rupture, thrombosis and acute sense of vital cardiovascular and cerebrovascular events. [0003] Atherosclerotic plaque neovascularization vascular imaging techniques includi...

Claims

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Application Information

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IPC IPC(8): A61K49/12A61K49/16A61K49/18A61K49/00A61K49/22A61K41/00A61K9/51A61K47/34A61K47/42A61P9/10
CPCA61K49/126A61K49/16A61K49/1857A61K49/1875A61K49/0002A61K49/221A61K49/225A61K49/223A61K41/0033A61K9/5153A61K9/5169A61P9/10Y02A50/30
Inventor 冉海涛姚剑挺杨卓文吴长君
Owner THE SECOND AFFILIATED HOSPITAL OF CHONGQING MEDICAL UNIV
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