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Low-renal-toxicity protein-ferric oxide composite nano magnetic resonance contrast agent as well as preparation method and application thereof

A magnetic resonance contrast agent, iron oxide technology, applied in the field of medical materials, can solve the problem of unverified contrast effect of magnetic resonance imaging nano-contrast agent, large inorganic core particle size of magnetic resonance imaging nano-contrast agent, limited angiography effect and biological safety. problems, such as low cost, high synthesis efficiency, low r1 value and saturation magnetization

Pending Publication Date: 2022-04-22
HEFEI INSTITUTES OF PHYSICAL SCIENCE - CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, GBCAs have several disadvantages in clinical applications: GBCA complexes are usually rapidly excreted through urine, which prevents their use in high-resolution imaging that requires longer scan times
However, this document did not verify the contrast effect of the magnetic resonance imaging nanocontrast agent prepared by it, and the preparation method is divided into first preparing Fe 2 o 3 SPs, followed by BSA-coated Fe 2 o 3 SPs, the steps are cumbersome, the inorganic core particle size of the magnetic resonance imaging nano-contrast agent obtained is large, it is not easy to be absorbed, and it is difficult to clear through the kidneys, which limits its angiographic effect and biological safety

Method used

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  • Low-renal-toxicity protein-ferric oxide composite nano magnetic resonance contrast agent as well as preparation method and application thereof
  • Low-renal-toxicity protein-ferric oxide composite nano magnetic resonance contrast agent as well as preparation method and application thereof
  • Low-renal-toxicity protein-ferric oxide composite nano magnetic resonance contrast agent as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0051] Example 1: Preparation and characterization of low nephrotoxic protein - iron oxide composite nano magnetic resonance contrast agent

[0052] 1) Preparation of low nephrotoxic protein-iron oxide composite nano magnetic resonance contrast agent

[0053] This embodiment uses a chemical co-precipitation method to prepare a variety of Fe having different Fe and BSA molar proportion relationships to Fe 2 O 3Magnetic resonance contrast agent for inorganic cores (i.e. BSA-wrapped Fe 2 O 3 , hereinafter referred to as Fe 2 O 3 @BSA nanoparticles), also prepared to Fe 3 O 4 Magnetic resonance contrast agent for inorganic cores (i.e. BSA-wrapped Fe 3 O 4 , hereinafter referred to as Fe 3 O 4 @BSA nanomelets), Fe 2 O 3 @BSA nanoparticles and Fe 3 O 4 @BSA nanoparticles are collectively referred to as iron oxide @BSA nanoparticles, and the specific operation steps are:

[0054] 1.1, with ultrapure water to prepare 80mg / ml BSA solution (diluted to obtain 40mg / ml, 20mg / ml, 10mg / ...

Embodiment 2

[0085] Example 2: Preparation of magnetic resonance imaging nano contrast agent

[0086] The embodiment is intended to utilize a variety of having different Fe 2+ and Fe 3+ Molar ratio of iron salt solution to prepare magnetic resonance imaging nano contrast agent, which differs only from the preparation method provided in Example 1 is: preparation of iron salt solution according to the table 3 below (wherein FeSO 4 Solution and FeCl 3 The total amount of the solution added is 2 ml for example), followed by the addition of BSA solution in accordance with the molar ratio of Fe to BSA is 165:1, and then the NaOH solution (in accordance with steps 1.1 to 1.6 in the preparation method provided in Example 1) or sequentially added NaOH solution and excess hydrogen peroxide solution (according to steps 1.1 to 1.11 in the preparation method provided in Example 1), and finally a series of iron oxide @BSA nanoparticles were prepared.

[0087] Table 3: With different Fe 2+ and Fe 3+ Molar th...

Embodiment 3

[0092] Example 3: Fe 2 O 3 in vivo MR imaging of @BSA nanoparticles

[0093] This embodiment is Fe prepared in the above example 1 2 O 3 @BSA4 nanoparticles as an example of an in vivo MR contrast analysis of the nanoparticles provided by the present invention, including the following operations.

[0094] 3.1. Fe is passed through the tail vein 2 O 3 @BSA4 nanoparticles or Gd-DTPA (0.15 mmol Fe / Gd per kilogram of rat body weight) are injected intravenously into 6-week-old male Sprague Dawley (SD) rats (purchased from SMOX, with an average weight of 200 g, all rats are cared for according to the guidelines outlined in the Laboratory Animal Care and Use Guidelines).

[0095] 3.2. Intraperitoneal injection of 5% chloral hydrate anesthetized rats, check the sagittal slices (i.e., MRI scan rat results) before and after injection for 2 min, 5 min, 15 min, 30 min, 45 min, 60 min. MR contrast images were obtained using a 3T clinical MRI scanner, in which the T1-weighted image was acquired...

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Abstract

The invention discloses a low-renal-toxicity protein-ferric oxide composite nano magnetic resonance contrast agent as well as a preparation method and application thereof, and belongs to the technical field of medical materials. The preparation method of the magnetic resonance contrast agent comprises the following steps: mixing functional protein with a ferric salt solution formed by mixing Fe < 2 + > and Fe < 3 + >, and adding a NaOH solution into the mixed solution or sequentially adding the NaOH solution and an excessive hydrogen peroxide solution, so that the protein-ferric oxide composite nano magnetic resonance contrast agent can be prepared by a one-pot in-situ method. The contrast agent takes ferric oxide as a core, and the functionalized protein is wrapped on the core, so that the contrast agent has high uniformity, hydrophilicity and monodispersity, low renal toxicity and good biocompatibility, and can be used as a safe magnetic resonance contrast agent.

Description

Technical field [0001] The present invention belongs to the field of medical materials technology, specifically relates to a low nephrotoxic protein - iron oxide composite nano magnetic resonance contrast agent and preparation method and application thereof. Background [0002] Magnetic resonance imaging (MRI) technology has become a powerful tool for current medical diagnosis due to its non-invasive and radiation-free technology, and in order to achieve better imaging results, about 40-50% of contrast agents are currently used for MRI detection. Magnetic resonance imaging agents are usually divided into two categories: longitudinal (T1) contrast agents and lateral (T2) contrast agents according to the effect on longitudinal or transverse relaxation. [0003] T1 contrast agents with positive enhancement effects are more suitable for high-resolution imaging, and the T1 contrast agent that is widely used clinically is gadolinium-based contrast agent (GBCA). However, GBCA has sever...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/18A61K49/14
CPCA61K49/1869A61K49/14
Inventor 马坤许帅王俊峰
Owner HEFEI INSTITUTES OF PHYSICAL SCIENCE - CHINESE ACAD OF SCI
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