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Low-oxygen dependent X-photodynamic nano photosensitizer as well as preparation method and application thereof

A photodynamic and dependent technology, applied in the field of biomedical nanomaterials, can solve the problems of high tissue oxygen partial pressure dependence, shallow penetration depth of excitation light source, and low penetration depth of excitation light source, so as to reduce tissue oxygen dependence. The effect of stability, unlimited penetration depth, and easy synthesis process

Active Publication Date: 2015-02-18
中国科学院上海硅酸盐研究所苏州研究院
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Problems solved by technology

Compared with traditional chemotherapy, radiotherapy and surgery, photodynamic therapy (PDT) has been widely studied due to its unique advantages of broad spectrum, flexibility and minimal invasiveness, but its wide application in clinical medicine There are still two key problems in the application: 1) The penetration depth of the excitation light source is shallow: the excitation light of traditional photosensitizers is usually in the ultraviolet-visible light band, and human tissues have strong absorption of light in this band, so there is a living body penetration depth of the excitation light source The shortcoming of low level makes PDT only applicable to superficial skin cancer, which becomes the main obstacle limiting its wide clinical application; 2) High dependence on tissue oxygen partial pressure: studies have shown that the usual PDT process is a type II process, That is, the triplet state of the organic photosensitizer molecule and the ground state oxygen molecule ( 3 o 2 ) undergoes energy transfer to produce cytotoxic singlet oxygen ( 1 o 2 ), as an oxygen consumption process, when the tissue oxygen partial pressure is low, its singlet oxygen production rate is greatly reduced, seriously affecting the therapeutic effect
[0003] Compared with photodynamic therapy, radiotherapy is not limited by the penetration depth of the living body, but it has the defect of low utilization rate of ray energy. In order to achieve the expected therapeutic effect, it is necessary to extend the course of radiotherapy to increase the radiation dose to the tumor area. Inevitably cause strong side effects on the body

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  • Low-oxygen dependent X-photodynamic nano photosensitizer as well as preparation method and application thereof
  • Low-oxygen dependent X-photodynamic nano photosensitizer as well as preparation method and application thereof
  • Low-oxygen dependent X-photodynamic nano photosensitizer as well as preparation method and application thereof

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preparation example Construction

[0057] The preparation method of the above-mentioned nano-photosensitizer may include: synthesizing the inner core of the nano-scintillation crystal, wrapping a silicon dioxide layer on the surface of the inner core, modifying the mercapto group on the silicon dioxide layer, covalently bonding the mercapto group on the silicon dioxide layer through the coordination between the mercapto group and the metal. The surface of the layer is adsorbed with ultra-small zinc oxide nanoparticles, and the outermost layer is modified with polyethylene glycol. Specifically, with LiYF 4 : Ce 3+ SiO 2 ZnO-PEG is taken as an example, which can be prepared by the following steps.

[0058] First, prepare LiYF 4 : Ce 3+ Nano-scintillation crystal core. It can be prepared by high-temperature pyrolysis of oleate, and the process may include the following operations:

[0059] 1-a) adding the precursor solution of rare earth ions into the mixed solution of octadecene and oleic acid, fully stirri...

Embodiment 1

[0092] Weigh 1.94mmol YCl 3 ·6H 2 O (588.5 mg) and 0.06 mmol CeCl 3 ·6H 2 O (22.4mg), dissolve with 2ml deionized water; Add 15ml oleic acid and 30ml octadecene in the there-necked flask of 100ml, add the rare earth ion precursor solution of preparation dropwise under stirring condition; Under argon protection condition, Raise the temperature of the system and keep it at 160°C for 1 hour; after ensuring that the water in the system is completely removed, stop heating and let it cool down to room temperature naturally to obtain a yellow clear solution; weigh 3mmolLiOH·H 2 O (125.9 mg) and 8 mmol NH 4 F (293.6mg), add 10ml of methanol and 2ml of acetic acid, ultrasonically dissolve, and add dropwise to the reaction system, stir at room temperature for 2h; heat up under the protection of argon, keep it at 120°C for 1h, and remove the Methanol and acetic acid; add a condensing reflux tube, raise the temperature of the system to 280°C and keep it warm for 1.5h to carry out the ...

Embodiment 2

[0146] Weigh 1.94mmol YCl 3 ·6H 2 O (588.5 mg) and 0.1 mmol CeCl 3 ·6H 2 O (37.3mg), dissolve with 2ml deionized water; Add 20ml oleic acid and 20ml octadecene in the there-necked flask of 100ml, add the rare earth ion precursor solution of preparation dropwise under stirring condition; Under argon protection condition, Raise the temperature of the system and keep it at 160°C for 1 hour; after ensuring that the water in the system is completely removed, stop heating and let it cool down to room temperature naturally to obtain a yellow clear solution; weigh 3 mmol LiOH·H 2 O (125.9 mg) and 8 mmol NH 4 F (293.6mg), add 10ml of methanol and 2ml of acetic acid, ultrasonically dissolve, and add dropwise to the reaction system, stir at room temperature for 2h; heat up under the protection of argon, keep it at 120°C for 1h, and remove the Methanol and acetic acid; add a condensing reflux tube, raise the temperature of the system to 280°C and keep it warm for 1.5h to carry out the...

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Abstract

The invention relates to a low-oxygen dependent X-photodynamic nano photosensitizer as well as a preparation method and an application thereof. The low-oxygen dependent X-photodynamic nano photosensitizer comprises nano scintillation crystal particles capable of converting a high-energy radiation ray into an ultraviolet light, a silicon dioxide layer cladded on the surface of the nano scintillation crystal, zinc oxide nanoparticles loaded on the outer surface of the silicon dioxide layer, and polyethylene glycol grafted on the surfaces of the zinc oxide nanoparticles. The nano scintillation crystal capable of converting the high-energy radiation ray into the ultraviolet light is taken as a functional kernel; the nano scintillation crystal can emit a characteristic ultraviolet ray when being irradiated by an X ray; and the characteristic ultraviolet ray can be efficiently absorbed by shell ZnO semiconductor quantum dots, so as to generate electron hole pairs. A lot of high-activity hydroxyl radicals (.OH) and superoxide anions (.O2<->) are generated by complicated physical and chemical reaction, so as to damage cancer cells.

Description

technical field [0001] The invention relates to a hypoxia-dependent X-ray dynamic nano-photosensitizer and its preparation method and application, belonging to the technical field of biomedical nano-materials. Background technique [0002] Malignant tumor is a kind of special disease that seriously threatens human health, and its treatment has attracted more and more attention. Photodynamic therapy (PDT) is an efficient cancer treatment technology that has emerged in recent years. The entire process involves three non-toxic elements, namely light of a specific wavelength (Light), photosensitizer molecules (PS) and oxygen ( o 2 ). The mechanism of action can be briefly described as that light of a specific wavelength activates the photosensitizer to generate cytotoxic reactive oxygen species through complex photochemical and physical processes, thereby selectively killing rapidly proliferating cells. Compared with traditional chemotherapy, radiotherapy and surgery, photody...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K41/00A61K47/34A61P35/00
Inventor 张辰步文博施剑林
Owner 中国科学院上海硅酸盐研究所苏州研究院
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