A tumor-targeted hollow core-shell structure nano-diagnostic agent and its preparation method and application

A core-shell structure, tumor-targeting technology, applied in the direction of anti-tumor drugs, preparations for in vivo tests, medical preparations with non-active ingredients, etc., can solve the problem of limited treatment efficiency, low photosensitizer loading, and affecting energy transfer Efficiency and other issues, to achieve the effect of increasing the load, increasing the load, and reducing agglomeration

Active Publication Date: 2017-10-24
FUJIAN INST OF RES ON THE STRUCTURE OF MATTER CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, the therapeutic efficiency of these therapeutic agents is limited. The main reason is that the loading of the photosensitizer is too low. The loaded photosensitizer contains a conjugated aromatic ring and is easy to agglomerate and self-quenches. The distance between the photosensitizer and the upconverting nanoparticles is too large to affect energy transfer efficiency

Method used

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  • A tumor-targeted hollow core-shell structure nano-diagnostic agent and its preparation method and application
  • A tumor-targeted hollow core-shell structure nano-diagnostic agent and its preparation method and application
  • A tumor-targeted hollow core-shell structure nano-diagnostic agent and its preparation method and application

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0057] Embodiment 1: Preparation of nano-diagnostic agent loaded with monocarboxyzinc phthalocyanine (ZnPc-COOH)

[0058] (1) Preparation of hexagonal NaLuF based on thermal decomposition method 4 :Gd / Yb / Er nanocrystal

[0059] Weigh sodium trifluoroacetate, lutetium trifluoroacetate, gadolinium trifluoroacetate, ytterbium trifluoroacetate and erbium trifluoroacetate at room temperature (a total of 2mmoL, the molar ratio of each element is 1 lutetium: 0.6 gadolinium: 3Na: 0.36 ytterbium: 0.04 Erbium) to a three-hole flask, add 6mL oleic acid, 3mL oleylamine and 3mL octadecene as a solvent; heat up to 300°C after heating under an inert atmosphere until the above-mentioned trifluoroacetate is dissolved, and cool naturally to room temperature, precipitated and washed to obtain NaLu(Gd)F 4 : Yb / Er nanocrystals.

[0060] NaLu(Gd)F 4 :Yb / Er joins in 6mL oleic acid and 6mL octadecene solution, adds sodium trifluoroacetate, lutetium trifluoroacetate, ytterbium trifluoroacetate and...

Embodiment 2

[0067] Embodiment 2: the preparation of the nano-therapeutic agent loaded with Rose Bengal (RB)

[0068] (1) Preparation of hexagonal NaLuF based on thermal decomposition method 4 :Gd / Yb / Er nanocrystal

[0069] Weigh sodium trifluoroacetate, lutetium trifluoroacetate, gadolinium trifluoroacetate, ytterbium trifluoroacetate and erbium trifluoroacetate at room temperature (a total of 2mmoL, the molar ratio of each element is 1 lutetium: 0.6 gadolinium: 3Na: 0.36 ytterbium: 0.04 Erbium) to a three-hole flask, add 6mL oleic acid, 3mL oleylamine and 3mL octadecene as a solvent; heat up to 300°C after heating under an inert atmosphere until the above-mentioned trifluoroacetate is dissolved, and cool naturally to room temperature, precipitated and washed to obtain NaLu(Gd)F 4 : Yb / Er nanocrystals. NaLu(Gd)F 4 : Yb / Er was added to 6mL oleic acid and 6mL octadecene solution, adding sodium trifluoroacetate, lutetium trifluoroacetate, ytterbium trifluoroacetate and erbium trifluoroac...

Embodiment 3

[0076] Example 3: Application performance detection of nano-therapeutic agent loaded with ZnPc-COOH

[0077] (1) Detection of singlet oxygen under 980° light: as Figure 7 As shown, the nano-medicine prepared in Example 1 has a power of 1W / cm 2 980nm laser irradiation for 26 minutes, the singlet oxygen produced can reduce the probe 1,3-diphenylisobenzofuran (DPBF) by 93%, while other comparison materials (including ordinary silica shell and ordinary core-shell structure) only decreased by about 50%, indicating that the nano-medicine can produce more singlet oxygen.

[0078] (2) In vitro photodynamic therapy effect detection of human lung cancer cells (H1299): such as Figure 8 As shown, the nano-therapeutic agent prepared in Example 1 was incubated with human lung cancer cells (H1299) for 4 hours, washed with PBS, and tested for photodynamic therapy. The cell survival rate was calculated by the MTT method. The power is 0.5W / cm 2 980nm laser irradiation for 10 minutes, when...

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Abstract

The invention relates to a tumor-targeted hollow core-shell structure nano diagnosis-treatment agent and a preparation method thereof. The nano diagnosis-treatment agent comprises an upconversion nanoparticle inner core, an organic-inorganic hybrid silica shell layer and an intermediate cavity structure, can improve the load capacity of a photosensitizer and reduce the photosensitizer aggregation, and can specifically recognize cancer cells by connecting tumor-targeted molecules (such as urokinase ammonia terminal fragments) to the surface; under the irradiation of 980 nm laser, a visible light emission sensitizing photosensitizer of the nano diagnosis-treatment agent generates singlet oxygen, so that the photodynamic therapy of cancer cells can be performed; in addition, the nano diagnosis-treatment agent can be used for the upconversion luminescence and CT dual-mode imaging by utilizing the upconversion luminescence and strong X-ray absorption characteristics.

Description

technical field [0001] The invention belongs to the technical field of nano-biological materials, and in particular relates to a tumor-targeted nano-diagnosis and treatment agent with hollow core-shell structure and its preparation method and application. Background technique [0002] With the development of biomedicine, the multifunctional combination of diagnosis and treatment (referred to as diagnosis and treatment) has become a new trend. Diagnosis and treatment technology can reduce the risk and pain caused by multiple drug administration or surgery. In order to achieve accurate diagnosis and efficient treatment, the designed diagnostic agents often need to have various functions such as lesion targeting, multimodal imaging and treatment. Rare earth-doped upconversion nanomaterials can convert near-infrared light into visible light, so they have important prospects in the development of non-invasive diagnostic agents. Due to the characteristics of low toxicity, photob...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K49/00A61K41/00A61K9/51A61K49/18A61K49/08A61K47/04A61K47/22A61P35/00
Inventor 陈学元卢珊涂大涛
Owner FUJIAN INST OF RES ON THE STRUCTURE OF MATTER CHINESE ACAD OF SCI
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