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Up-conversion nanoparticle non-oxygen-dependent photodynamic diagnosis and treatment probe and preparation method

A nanoparticle and photodynamic technology, applied in the field of upconversion nanoparticle oxygen-independent photodynamic diagnosis and treatment probe and preparation, can solve the problems of reduced curative effect, low treatment depth, poor photostability of photosensitizers, etc.

Active Publication Date: 2021-09-14
XIDIAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, photosensitizers need to rely on partial pressure of oxygen in the process of photodynamic therapy, and the hypoxic environment of tumors greatly reduces their curative effect; most of the excitation light wavelengths used in clinical photosensitizers are in the visible light region, due to the scattering and absorption of short-wavelength biological tissues Strong, so the treatment depth is greatly limited, and the traditional photosensitizers have poor photostability due to the destruction of the conjugated system and the blockage of electronic transitions due to their conjugated structures under long-term illumination. needle application
[0003] To sum up, the problems existing in the prior art are: photosensitizers need to rely on partial pressure of oxygen in the process of photodynamic therapy, and the hypoxic environment of tumors greatly reduces its curative effect; the treatment depth of traditional photosensitizers is low, and it is difficult to achieve deep treatment. Penetration and poor photostability of traditional photosensitizers limit the application of photodynamic nanoprobes
[0005] How to solve the problems of tumor hypoxia inhibition, low treatment depth and poor stability in the process of traditional photosensitizer therapy is the key to improving the effect and application of photodynamic therapy
The hypoxic microenvironment of the tumor due to its vigorous metabolism is severely inhibited by clinical oxygen-dependent photodynamic therapy, resulting in very limited PDT treatment effect. Therefore, how to overcome or avoid the hypoxic inhibition process is the key to achieving efficient PDT treatment of tumors
The photosensitizers used in traditional PDT treatment have poor photostability, and the excitation light source used has poor biological tissue penetration and severe oxygen dependence, which limits its clinical application

Method used

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  • Up-conversion nanoparticle non-oxygen-dependent photodynamic diagnosis and treatment probe and preparation method

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preparation example Construction

[0047] Such as figure 1 As shown, the preparation method of the up-conversion nanoparticle non-oxygen-dependent photodynamic diagnosis and treatment probe provided by the embodiment of the present invention includes the following steps:

[0048] S101: Positively charged modified upconversion nanoparticles are coated with negatively charged azo compounds, and 808nm excited upconversion nanoparticles are synthesized by high-temperature thermal reaction of rare earth hydrochloride; using surfactant CO520 and ethyl orthosilicate, through reaction Phase microemulsion method, depositing a layer of mesoporous silica on the surface of upconversion nanoparticles, and using mPEG-Saline to stabilize, and coating negatively charged azo compounds into mesoporous silica by electrostatic adsorption;

[0049] S102: Negatively charged modified upconverting nanoparticles coated with negatively charged azo compounds; 808nm excited upconverting nanoparticles were synthesized by high-temperature t...

Embodiment 1

[0061] NaYF4:30%Yb,0.5%Tm@NaYF4:10%Yb@NaNdF4:10%Yb@mSiO 2 / the preparation of azobisisobutylimidazoline hydrochloride probe;

[0062] Synthesis principle: First, 808nm-excited up-conversion nanoparticles are generated through the high-temperature thermal reaction of rare earth hydrochloride. Using surfactant CO520 and ethyl orthosilicate, one can be deposited on the surface of the above-mentioned up-conversion nanoparticles by the inverse microemulsion method. Layer mesoporous silica, stabilized by mPEG-Saline, and finally coat the azo compound into the mesoporous silica by electrostatic adsorption.

[0063] Concrete synthetic steps:

[0064] 1. Synthesis of CSS structure upconversion nanoparticles excited by 808nm

[0065] (1)NaYF 4 : Synthesis of 30%Yb, 0.5%Tm (2mmol system)

[0066] Weigh 0.2714g yttrium chloride hydrate, 0.1676g ytterbium chloride hydrate, 0.0027g thulium chloride hydrate, add to a 100mL three-neck flask, add 12mL oleic acid, 30mL 1-octadecene, seal w...

Embodiment 2

[0085] Preparation of NaYF4:30%Yb,0.5%Tm@NaYF4:10%Yb@NaNdF4:10%Yb@CaP / azobisisobutylimidazoline hydrochloride probe

[0086] Experimental principle: Firstly, the upconversion nanoparticles excited by 808nm are synthesized through the high-temperature thermal reaction of rare earth hydrochloride, and then transferred to the water phase by the method of citrate ion ligand substitution. The azo compound is adsorbed on the PEG molecular chain through the electrostatic interaction between PEG and the negatively charged dye, and the PEG after the adsorption of the azo compound self-assembles in the citrate ethanol / water solution to form a template; by adjusting the pH and adding phosphate mineralization to make Calcium phosphate is deposited on the surface of upconverting nanoparticles to form dye-coated nanoparticles;

[0087] Concrete synthetic steps:

[0088] 1. Synthesis of CSS structure upconversion nanoparticles excited by 808nm

[0089] (1)NaYF 4 : Synthesis of 30%Yb, 0.5%...

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Abstract

The invention belongs to the technical field of organic compounds, and discloses an upconversion nanoparticle oxygen-independent photodynamic diagnosis and treatment probe and a preparation method, which are composed of a modified upconversion nanoparticle and an azo compound; the modified upconversion nanoparticle is composed of It is composed of positively charged modified upconversion nanoparticles and negatively charged modified upconversion nanoparticles; azo compounds are organic molecules containing nitrogen and nitrogen double bonds that can be photolyzed under ultraviolet light; composed of negatively charged azo compounds and belts The composition of positively charged azo compounds. The present invention is based on the photodynamic probe of up-conversion nanoparticles, and its photodynamic therapy process can be triggered by near-infrared light, which overcomes the problem of insufficient treatment depth caused by the need to directly use ultraviolet / visible light sources in traditional photodynamic therapy. At the same time, the probe will emit light in the second region of near-infrared under the irradiation of near-infrared light, which can be used to monitor the in vivo aggregation and metabolic status of the probe, and to locate the tumor tissue before treatment.

Description

technical field [0001] The invention belongs to the technical field of organic compounds, in particular to an upconversion nanoparticle non-oxygen-dependent photodynamic diagnosis and treatment probe and a preparation method. Background technique [0002] At present, the existing technologies commonly used in the industry are as follows: At present, the clinical treatment methods for tumors are mainly three categories: radiotherapy, chemotherapy and surgery. The characteristics have gradually attracted attention, and its main mechanism is that the photosensitizer absorbs the excitation light to generate reactive oxygen species, thereby damaging the protein or DNA of tumor cells, and then achieving the purpose of inhibiting tumors. At present, in addition to applying photosensitizer drugs alone in tumor treatment, more photosensitizers are combined with nanocarriers to improve the depth and targeting of treatment by constructing a composite probe. Common nanocarriers include...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K41/00A61K9/14A61K49/00A61K47/60A61K47/02A61K47/34A61P35/00
CPCA61K41/0057A61K47/02A61K47/34A61P35/00
Inventor 张瑞丽王忠良王永东白明利袁慧娟贾茜闫如玉田捷
Owner XIDIAN UNIV