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Cell nucleus targeted radiosensitizer and preparation method thereof

A technology of cell nuclei and sensitizers, applied in the field of nano-biomedicine, can solve the problems of single imaging mode, low efficiency of targeted transport, lack of synergy, etc., and achieve high imaging sensitivity and spatial resolution, good diagnosis and treatment efficiency, and high-efficiency The effect of synergistic treatment

Inactive Publication Date: 2015-01-21
SHANGHAI INST OF CERAMIC CHEM & TECH CHINESE ACAD OF SCI
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] Based on the current severe cancer situation and the development trend of nano-biomedicine in the future, the purpose of the present invention is to provide a nuclear-targeted radiosensitizer to overcome the single imaging mode and low drug delivery efficiency in the field of cancer diagnosis and treatment. , lack of synergistic effect between chemotherapy and radiotherapy, etc., in order to realize the accurate diagnosis of magnetic resonance / up-conversion luminescence dual-mode for malignant tumor cell nuclei and the efficient synergistic treatment of chemotherapy / radiotherapy, and significantly improve the effect of chemotherapy / radiotherapy synergistically destroying DNA. Play an active role in the field of early diagnosis and treatment of cancer in the future

Method used

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  • Cell nucleus targeted radiosensitizer and preparation method thereof
  • Cell nucleus targeted radiosensitizer and preparation method thereof
  • Cell nucleus targeted radiosensitizer and preparation method thereof

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preparation example Construction

[0055] First, refer to figure 1 with image 3 The preparation method of core / shell cavity mesoporous silica structure (RUMSNs) is described. The preparation of the core / shell cavity mesoporous silica structure mainly includes: the preparation of the inner core gadolinium-doped upconversion luminescent nanoparticle core, the wrapping of the mesoporous silica shell, and the formation of the cavity between the inner core and the outer shell. The formation of the cavity can be achieved by two methods: introducing a solid silicon oxide layer between the inner core and the mesoporous silicon oxide shell and then etching it away (see figure 1 Steps 1, 2, 3); or directly form a mesoporous silica shell on the outer surface of the core and etch away part of the mesoporous silica on the inner side (see figure 1 Steps 4, 5, and 6). An example of the preparation of core / shell cavity mesoporous silica structures (RUMSNs) is specifically described below.

[0056] (1) Preparation of core gadolin...

Embodiment 1

[0068] Example 1 Preparation of gadolinium-doped up-conversion fluorescent nanoparticles UCNPs

[0069] 1. Preparation of rare earth chlorides. Weigh 1.28mmol (388.3008mg) YCl respectively 3 -6H 2 O, 0.36mmol (139.4964mg) YbCl 3 -6H 2 O, 0.04mmol (15.2684mg) ErCl 3 -6H 2 O, 0.02mmol (5.5087mg) TmCl 3 , 0.3mmol (79.083mg) GdCl 3 -6H 2 O. These powders are placed in the same sample bottle, then dissolved in 4mL deionized water, and transferred to a 100mL three-necked flask;

[0070] 2. Add 15 mL of oleic acid and 30 mL of octadecene to a three-necked flask, and stir at room temperature for 1 hour. Then argon gas was passed for 5 minutes to remove the air in the bottle, and the system began to slowly remove water. Raise the temperature to 80 degrees and keep it for 1 hour or longer (removing free water); then raise it to 120 degrees and keep it for 1 hour; then raise it to about 156 degrees and keep it for 1 hour to obtain a yellow clear liquid. Stop heating and let the system cool...

Embodiment 2

[0075] Example 2 The outer surface of UCNPs is coated with solid silicon oxide UCNPsSiO 2

[0076] The inverse microemulsion method is adopted to realize the encapsulation of solid silica. Add 1 mL of NP-5 to 20 mL of cyclohexane and stir magnetically for 40 minutes. 1.5mL 100mM UCNPs cyclohexane solution was added to the NP-5 / cyclohexane system, colorless and transparent, sealed and stirred for 3h. 0.14 mL 30% ammonia water was added dropwise to the mixed solution, and sealed and stirred for 2 hours. 0.16mL TEOS was dissolved in 1ml cyclohexane and introduced into the system at a rate of 1mL / h. After 36 hours, methanol was added to destroy the inverse microemulsion system. After stirring for 30 minutes, the mixture was collected by centrifugation. The whole process was washed with ethanol and dispersed by ultrasound, repeated three times, and finally dispersed in 5 mL of deionized water. See the TEM image of the product Figure 4 In (b 2 ).

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Abstract

The invention relates to a cell nucleus targeted radiosensitizer and a preparation method thereof. The cell nucleus targeted radiosensitizer adopts a nucleus / shell cavity mesoporous silica structure, and comprises a mesoporous silica shell provided with a cavity, gadolinium-doped up-conversion fluorescence nano-particles positioned in the cavity of the mesoporous silica shell, a radiosensitization drug loaded in the cavity of the mesoporous silica shell, and a cell nucleus targeted ligand in covalent linkage with the surface of the mesoporous silica shell. According to the invention, the cell nucleus targeted radiosensitizer can realize the magnetic resonance / up-conversion luminescence dual-mode precise diagnosis and chemotherapy / radiotherapy efficient collaborative treatment for malignant tumor cell nucleuses, and is expected to achieve the optimal diagnosis and treatment efficiency.

Description

Technical field [0001] The invention relates to a nuclear targeted radiotherapy sensitizer and a preparation method thereof, belonging to the field of nano biomedicine. Specifically, this nuclear-targeted radiotherapy sensitizer is a core / shell cavity mesoporous silica structure with a size below 50 nm. The inner core gadolinium doped with upconversion fluorescent particles can realize the dual-mode imaging diagnosis of magnetic resonance / upconversion luminescence for tumor lesions; the mesoporous pores and cavities can be loaded with mitomycin MMC, a radiosensitizing drug that efficiently destroys the function of DNA. Thereby, the radiosensitization in the nucleus can be realized, the effect of chemotherapy / radiotherapy coordinated treatment can be greatly improved, and the best diagnosis and treatment efficiency can be achieved. Background technique [0002] Currently, chemotherapy and radiotherapy are commonly used clinically to treat cancer, but they often have little effect...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K49/06A61K49/18A61K49/00A61K31/407A61K33/24A61K31/337A61K47/42A61K47/04A61P35/00
Inventor 范文培步文博施剑林
Owner SHANGHAI INST OF CERAMIC CHEM & TECH CHINESE ACAD OF SCI
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